The effect of L-theanine on the oxidant-antioxidant balance in serum and lung tissue in experimentally induced sepsis in rats

Sepsis induces lung injury and respiratory distress syndrome and is therefore potentially fatal. L-theanine (LT), an amino acid found in tea, is a bioactive compound with an important antioxidant, anti-inflammatory, and antifibrotic properties. The purpose of this study was to evaluates whether, LT exhibits protective effects against lung tissue damage by determining its effect on oxidative stress, inflammation and mineral levels in an experimental model of cecal ligation and perforation (CLP)-induced sepsis in rats. Rats were randomly divided into three groups (n=6): sham, CLP, and CLP+LT. LT was administered intraperitoneally (750 mg/kg) in two equal doses immediately and 12 h after surgery. Malondialdehyde (MDA), advanced protein oxidation product (AOPP), myeloperoxidase (MPO), total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI), and ischemia modified albumin (IMA) values were determined spectrophotometrically. Serum elements (Na, K, Mg, Ca, and Fe), albumin, glucose, triglyceride, and lactate levels were determined using an autoanalyzer. Lung tissues were also examined histopathologically. Treatment of septic rats with LT significantly reduced oxidative stress and inflammation in lung tissues and serum. LT also increased albumin and Na levels and reduced triglyceride levels in serum. In conclusion, LT treatment may exhibit a preventive effect against sepsis-induced lung injury by reducing oxidative stress and inflammation, and by regulating osmotic balance.

Correlation analysis between the expression of cannabinoid 2 receptor and the related indicators of pyroptosis in sepsis / 中华急诊医学杂志

Objective:To explore the correlation between cannabinoid 2 receptor (CB2R) and pyroptosis-related indicators in mice with septic lung injury.Methods:Mice were randomly (ramdon number) divided into four groups ( n=6 per group): sham operation group (sham), mild sepsis group (ALIMi), moderate sepsis group (ALIMo) and severe sepsis group (ALIS). The model of septic lung injury was established by cecal ligation and puncture. The wet-dry weight ratio of lung tissues and lung injury scores were measured 12 hours after operation. The expression of CB2R protein was measured by western blot, and the expression of mRNA of CB2R, NLRP3, caspase-1/11, GSDMD were detected by RT-PCR. Meanwhile ELISA was used to measure the level of inflammatory factor IL-6 and TNF-α. SPSS 22.0 software was used for data analysis. Multiple comparison was analyzed by one-way analysis of variance (one-way ANOVA) and comparison between two groups was performed by LSD test or Games-Howell test. Then, the correlation between the expression of CB2R mRNA and the level of inflammatory cytokines as well as the expression of the pyroptosis-related indicators mRNA was analyzed by pearson correlation analysis, respectively. Results:The statistical value F was obtained by one-way ANOVA and comparison between two groups was performed. Compared to sham group, all above indicators increased with the aggravation of inflammation in the sepsis groups ( P<0.05). Compared to ALIMi group, the concentrations of IL-6 [(277.31±41.07) vs.(140.09±27.56), P<0.05] and TNF-α [(501.09±73.91) vs. (261.36±40.73), P<0.05] in lung tissue homogenate increased in ALIMo group. And the level of CB2mRNA [(2.99±0.28) vs. (2.02±0.19), P<0.05], the expression of CB2 protein [(0.44±0.08) vs.(0.23±0.05), P<0.05] and the level of NLRP3 [(2.53±0.26) vs.(1.61±0.15), P<0.05], caspase-1 [(6.02±0.35) vs.(3.60±0.38), P<0.05], caspase-11 [(11.43±0.83) vs.(6.30±0.65), P<0.05] and GSDMD [(10.46±0.62) vs. (5.67±0.54), P<0.05] mRNA also increased. Compared to ALIMo group, the concentrations of IL-6 [(475.90±67.65) vs. (277.31±41.07), P<0.05] and TNF-α [(713.93±58.85) vs. (501.09±73.91), P<0.05] in lung tissue homogenate increased in ALIS group. And the level of CB2mRNA [(4.00±0.19) vs.(2.99±0.28), P<0.05], the expression of CB2 protein [(0.61±0.05) vs.(0.44±0.08), P<0.05] and the level of NLRP3 [(4.75±0.40) vs.(2.53±0.26), P<0.05], caspase-1 [(8.76±0.72) vs.(6.02±0.35), P<0.05], caspase-11 [(16.31±1.13) vs.(11.43±0.83), P<0.05] and GSDMD [(16.46±1.22) vs. (10.46±0.62), P<0.05] mRNA also increased. Furthermore, correlation analysis showed that there was a highly positive correlation between the expression of CB2R mRNA and the expression of mRNA of NLRP3, caspase-1/11, and GSDMD respectively ( r>0.9, P<0.01). Conclusion:The correlation between the aggravation of inflammation, the indicators of pyroptosis and CB2R mRNA was highly positive in different degrees of septic lung injury. Consequently, CB2R may play a role in the regulatory process of inflammation.

Mechanisms of sodium butyrate inhibition of microglia inflammatory activation in hippocampus via Toll-like receptor 4/nuclear factor-κB p65 pathway / 中华危重病急救医学

Objective:To investigate the effects of sodium butyrate (NaB) on long-term anxiety like behavior and inflammatory activation of microglia in the hippocampus of sepsis-associated encephalopathy (SAE) mice.Methods:① Animal experiment: fifty C57BL/6 mice aged 6-8 weeks were randomly divided into Sham group (only the cecum was found by laparotomy without perforation or ligation), and SAE model group caused by cecal ligation and puncture (CLP; SAE model group, the cecum was found by laparotomy and perforated after ligation. The open field test indicated that the ability of independent exploration decreased and showed anxiety like behavior, which proved that the SAE model was successfully replicated) and NaB pretreatment group was established (NaB was administered at a dose of 500 mg·kg -1·d -1 for 3 days before modeling, and the same dose once a day for 3 days after modeling). Open field test was used to detect the anxiety like behavior of mice at 7 days. The protein expressions and content changes of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in hippocampus of mice at 1 day and 3 days after operation were detected by Western blotting and enzyme linked immunosorbent assay (ELISA). Immunofluorescence staining was used to observe microglia labeled protein ionized calcium bindingadaptor molecule-1 (Iba-1) and TNF-α protein co localization. ② Cell experiment: mouse microglia cell line BV-2 microglia were divided into blank control group, lipopolysaccharide (LPS) group (cells were treated with 1 mg/L LPS), and NaB treatment group (cells were treated with 1 mg/L LPS+5 mmol/L NaB). The protein expressions of IL-1β, TNF-α, Toll-like receptor 4 (TLR4), phosphorylated nuclear factor-κB p65 (p-NF-κB p65), nuclear factor-κB p65 (NF-κB p65) and NF-κB inhibitor protein-α (IκB-α) were detected by Western blotting. The expressions of Iba-1 and TNF-α in each group were observed by immunofluorescence. Results:① Animal experiment: compared with the Sham group, the distance and duration of movement in the central area, the total distance moved of mice decreased 7 days after the establishment of SAE model group were decreased [distance of movement in the central area (mm): 13.45±3.97 vs. 161.44±27.00, duration of movement in the central area (s): 1.82±0.58 vs. 13.45±2.17, the total distance moved (mm): 835.01±669.67 vs. 2 254.51±213.45, all P < 0.05]. In the hippocampus tissues of mice, a large number of nerve nuclei were pyknotic and deeply stained, and the arrangement of nerve cells was disordered. The cell bodies of microglia in mouse hippocampus increased significantly. The number of positive cells of Iba-1/TNF-α (Iba-1 +/TNF-α +) increased significantly. The contents and protein expression of proinflammatory factors TNF-α, IL-1β in hippocampal homogenate supernatant 3 days after operation in SAE model group were significantly higher than those in Sham group [TNF-α (ng/L): 119.17±18.40 vs. 90.18±21.17, IL-1β (ng/L): 407.89±70.64 vs. 313.69±34.63; TNF-α/GAPDH: 1.42±0.50 vs. 0.80±0.08, IL-1β/GAPDH: 1.27±0.22 vs. 0.85±0.25, all P < 0.05]. After intragastric administration of NaB, the distance and duration of movement in the central area of mice were significantly higher than those in SAE model group [distance of movement in the central area (mm): 47.39±15.63 vs. 13.45±3.97, duration of movement in the central area (s): 6.12±1.87 vs. 1.82±0.58, all P < 0.05]. There was no significant change in the total distance moved (mm: 1 550.59±1 004.10 vs. 835.01±669.67, P > 0.05). The pyknosis and deep staining of nerve nuclei in mice were significantly less than those in SAE model group. The number of Iba-1 +/TNF-α + positive cells decreased significantly. The contents and protein expression levels of proinflammatory factors TNF-α, IL-1β in hippocampal homogenate supernatant 3 days after operation were significantly lower than those in SAE model group [TNF-α (ng/L): 64.95±9.10 vs. 119.17±18.40, IL-1β (ng/L): 311.94±69.92 vs. 407.89±70.64; TNF-α/GAPDH: 1.02±0.36 vs. 1.42±0.50, IL-1β/GAPDH: 0.86±0.20 vs. 1.27±0.22, all P < 0.05]. ② Cell experiment: after LPS intervention, the fluorescence intensity of TNF-α in BV-2 cells was significantly enhanced, the protein expression levels of TNF-α, IL-1β, TLR4 and p-NF-κB p65 protein increased (TNF-α/GAPDH: 0.39±0.06 vs. 0.20±0.02, IL-1β/GAPDH: 0.27±0.03 vs. 0.19±0.01, TLR4/GAPDH: 0.55±0.12 vs. 0.33±0.09, p-NF-κB p65/NF-κB p65: 0.55±0.05 vs. 0.29±0.04, all P < 0.05), the expression level of IκB-α was lower than that in the control group(IκB-α/GAPDH: 0.54±0.06 vs. 0.81±0.03, P < 0.05). After NaB treatment, the fluorescence intensity of TNF-α in BV-2 cells was decreased. The protein expression levels of TNF-α, IL-1β, TLR4 and p-NF-κB p65 protein were significantly lower than that of LPS model group (TNF-α/GAPDH: 0.26±0.02 vs. 0.39±0.06, IL-1β/GAPDH: 0.11±0.04 vs. 0.27±0.03, TLR4/GAPDH: 0.28±0.14 vs. 0.55±0.12, p-NF-κB p65/NF-κB p65: 0.29±0.01 vs. 0.55±0.05, all P < 0.05), the protein expression level of IκB-α was significantly higher than that in the LPS group (IκB-α/GAPDH: 0.75±0.01 vs. 0.54±0.06, P < 0.05). Conclusion:NaB could antagonism the TLR4 activation induced by LPS, thus inhibiting p-NF-κB p65 nuclear transcription and IκB-α degradation. It can reduce microglia activation and secretion of inflammatory factors, and finally improve the inflammation in the hippocampus of septic mice and long-term anxiety like behavior.

Astragaloside IV Attenuates Polymicrobial Sepsis-Induced Cardiac Dysfunction in Rats via IKK/NF-κB Pathway / 中国结合医学杂志

OBJECTIVE@#To evaluate the protective effects of Astragaloside IV (AST) in a rat model of myocardial injury induced by cecal ligation and puncture (CLP).@*METHODS@#The model of sepsis-induced cardiac dysfunction was induced by CLP. Using a random number table, 50 specific pathogen free grade of Sprague Dawley rats were randomized into 5 groups: the sham group (sham), the model group (CLP, 18 h/72 h) and AST group (18 h/72 h). Except the sham group, the rats in other groups received CLP surgery to induce sepsis. CLP groups received intragastric administration with normal saline after CLP. AST groups received intragastric administration with AST solution (40 mg/kg) once a day. The levels of inflammatory mediators and oxidative stress markers in the serum of the septic rats were determined via enzyme-linked immunosorbent assay (ELISA) at different time point, such as interleukin 6 (IL-6), IL-10, high mobility group box-1 protein B1 (HMGB-1), superoxide dismutase (SOD), and malondialdehyde (MDA). Cardiac function was determined by echocardiography. Moreover, changes in myocardial pathology were evaluated using hematoxylin and eosin staining. The levels of lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB) were analysed to determine the status of CLP-induced myocardium. In addition, the apotosis of myocardial cells was analysed by terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL). The protein levels of B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X (Bax), IκB kinase α (IKKα), nuclear factor kappa B p65 (NF-κB p65) were detected by Western blot analysis. Moreover, survival rate was investigated.@*RESULTS@#AST improved the survival rate of CLP-induced rats by up to 33.3% (P<0.05). The cardioprotective effect of AST was observed by increased ejection fraction, fractional shortening and left ventricular internal diameter in diastole respectively (P<0.01 or P<0.05). Subsequently, AST attenuated CLP-induced myocardial apoptosis and the ratio of Bcl-2/Bax in the myocardium, as well as the histological alterations of myocardium (P<0.01 or P<0.05); the generation of inflammatory cytokines (IL-6, IL-10, HMGB-1) and oxidative stress markers (SOD, MDA) in the serum was significantly alleviated (P<0.01 or P<0.05). On the other hand, AST markedly suppressed CLP-induced accumulation of IKK-α and NF-κB p65 subunit phosphorylation (P<0.01 or P<0.05).@*CONCLUSIONS@#AST plays a significant protective role in sepsis-induced cardiac dysfunction and survival outcome. The possible mechanism of cardioprotection is dependent on the activation of the IKK/NF-κB pathway in cardiomyocytes.

Establishment of An Improved Rat Model of Sepsis Induced by Cecal Ligation and Puncture / 中国医学科学院学报

To establish an improved animal model of sepsis induced by cecal ligation and puncture(CLP). Ninety-six male Sprague-Dawley rats were randomly divided into sham operation group(=24),intubation group(=24),CLP group(=24),and CLP+intubation group(=24).The mortality rate,abdominal cavity condition,pathological changes and pathological scores of heart,lungs,liver,and kidneys of rats in each group were observed after modeling.Blood samples were obtained from the inferior vena cava for measuring the whole blood cells(WBC)and platelets(PLT)counts and analyzing serum interleukin(IL)-6,tumor necrosis factor(TNF)-α,serum troponin T(cTnT),creatine kinase-MB(CK-MB),alanine aminotransferase(ALT),aspartate aminotransferase(AST),total bilirubin(TBIL),creatinine(CREA),and blood urea nitrogen(BUN)levels.Blood gas analysis of the aorta was also performed. The mortality rates 24 h after modeling were 0 in sham operation group and intubation group,20.8% in CLP group,and 54.2% in CLP+intubation group.Pathologically,swelling and inflammatory cell infiltration in the heart,lungs,liver,and kidneys were seen in the CLP+intubation group,inflammatory cell infiltration in a single organ was seen in most rats in the CLP group,and no obvious swelling and infiltration of inflammatory cells was observed in the sham-operation group and intubation group.The myocardial histopathology score,lung tissue injury pathology score,and kidney tissue injury pathology score in both the sham-operation group and the intubation group were significantly lower than those in the CLP group and the CLP+intubation group(all =0.000).TNF-α,PaO,CK-MB,cTnT,AST,TBIL,BUN,and CREA were significantly different between sham-operation group and intubation group/CLP group/CLP+intubation group and between intubation group and CLP group/CLP+intubation group(all =0.000).The pH level was significantly different between sham operation group and intubation group/CLP group,between intubation group and CLP group/CLP+intubate group(all =0.000). Although both CLP and CLP+intubation can well mimic the pathophysiological mechanism of sepsis in rats,multiple organ dysfunction occurs in the latter.Thus,CLP+intubation can establish animal models of multiple organ dysfunction caused by sepsis induced by clinically effective abdominal infection.

Study of autophagy and expression of LC3/P62 in hepatocytes of septic mice / 中华急诊医学杂志

Objective To investigate the occurrence of hepatocyte autophagy and the expression of autophagy associated proteins at different time points in sepsis mice model established by cecal ligation and puncture.Methods Fifty male ICR mice aged 6-8 weeks were randomly (random number) divided into 5 groups:CLP 3 h group,CLP 6 h group,CLP 12 h group,CLP 24 h group and control group.The samples were collected at the corresponding time points after operation.Liver function was tested to obtain alanine aminotransferase (ALT) and aspartate aminotransferase (AST).The expression of TNF-α and IL-6 was detected by ELISA,the inflammation of liver tissue by HE staining while the ultrastructure of autophagosome and autolysosome in liver tissue was observed by electron microscopy.Meanwhile,the expression of LC3 and P62 was detected by Western blot.and the location and quantity of autophagosome was observed by Immunofluorescence.SPSS 21.0 was used for statistical analysis.Two independent sample t tests were performed to compare the two groups,and one-way ANOVA was used for comparison between multiple groups.Results ALT and AST increased significantly after CLP,and peaked at 12 h,respectively (137.8 ±11.94) U/L and (475.3 ±57.34) U/L.The expression of IL-6 peaked at 6 h (2589.63 ±27.96) pg/mL,and TNF-α peaked at 3 h (320.21±8.9) pg/mL.HE staining showed activation of Kupffer cells and infiltration of single granulocyte.Electron microscope showed the formation of autophagosome and autolysosome.Compared with the control group,the ratio of LC3 Ⅱ/Ⅰ increased first and then decreased,peaked at 6 h (t=13.35,P＜0.05).The content of P62 protein declined first and then went up,reaching the lowest level at 6 h (t=66.1 l,P＜0.05),contrary to the trend of LC3 Ⅱ/Ⅰ.Immunofluorescence results illustrated that the fluorescence intensity of LC3 reached its high point at 6 h (t=12.52,P＜0.05).Conclusions Autophagy occurred in the liver of sepsis mice model established by cecal ligation and puncture.The formation of autophagosome first increased and then decreased,reaching its peak at 6 h.

Pharmacokinetic and NMR metabolomics approach to evaluate therapeutic effect of berberine and Coptidis Rhizoma for sepsis / 中草药·英文版

Objective: Sepsis, a systemic response to infection, often leads to end-organ dysfunction. Despite its high rates of mortality and morbidity, its pathophysiology is still poorly understood. Coptidis Rhizoma and its main active alkaloid compound, berberine, have been as anti-bacterial and anti-inflammatory drugs used in clinic. The objective of this study was to gain more insights towards understanding the sepsis associated with drug absorption and disposition and treatments of berberine and Coptidis Rhizoma dynamically. Methods: Pharmacokinetic and metabolomic studies of Coptidis Rhizoma and its main active component berberine have been performed. Results: Cecal ligation and puncture (CLP) induced sepsis showed marked changes of metabolites concerning energy metabolism and amino acids metabolisms, which could be reversed towards the normal state by Coptidis Rhizoma and berberine. Conclusion: Berberine exhibited an equivalent and even better therapeutic effect than Coptidis Rhizoma.

Experimental study of cardiac function by high-resolution ultrasound in sepsis rats with cecal ligation and puncture / 中华危重病急救医学

To evaluate the cardiac function of cecal ligation and puncture (CLP) induced sepsis rats with high-resolution ultrasound. Methods According to the method of random number table, 48 adult male Sprague-Dawley (SD) rats were randomly divided into normal control group and sepsis 6, 12, 24, 30, 48 hours groups, with 8 rats in each group. The sepsis model was produced by CLP, and the rats in the normal control group were only anesthetized and resuscitated. The general situation after modeling in each group was observed, and the left ventricular function was assessed by high-resolution echocardiography at all the time points. The abdominal aorta blood of rats was collected, and the serum levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and MB isoenzyme of creatine kinase (CK-MB) were determined by enzyme-linked immunosorbent assay (ELISA). The myocardial tissue was harvested, and the pathological changes in myocardial tissue were observed by hematoxylin-eosin (HE) staining. Results The rats challenged to CLP displayed symptoms of sepsis, such as depression, ruffled fur, decreased diet and activity, and the symptoms became more obvious with the extension of time. High-resolution echocardiography could clearly show the structure of left ventricle in each group and obtain satisfactory M-mode echocardiography of left ventricle. The heart rate (HR) of rats in all sepsis groups was elevated with the increase in model time as measured by high-resolution ultrasound, and it was significantly higher than that in the normal control group at 12, 24, 30 hours (bpm: 359.66±23.33, 361.35±12.85, 392.67±11.33 vs. 306.24±29.79, all P < 0.05). Stroke volume (SV) and cardiac output (CO) in sepsis rats were decreased with the increase in model time, while left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) were increased first and then decreased, and SV and LVEF in sepsis 48 hours group were significantly lower than those in the normal control group [SV (μL): 78.43±17.52 vs. 122.61±15.88, LVEF: 0.763±0.018 vs. 0.902±0.011, both P < 0.05]. Left ventricular weight (LVW) in all sepsis groups was increased to different degrees as compared with that in the normal control group, as well as the left ventricular anterior and posterior wall thickness increased in diastole and systole. Compared with the normal control group, the left ventricular posterior wall thickness was increased significantly at the end of diastolic and systolic period in the sepsis 12 hours group, and the left ventricular anterior wall thickness was also increased significantly at the end of diastolic period in the sepsis 48 hours group. The serum levels of TNF-α, IL-1β and CK-MB in sepsis rats were increased first and then decreased with the extension of model making time. The above parameters in the sepsis 48 hours group were still significantly higher than those in the normal control group [TNF-α (ng/L): 61.59±3.99 vs. 16.87±4.89, IL-1β (ng/L):255.03±13.23 vs. 119.59±10.43, CK-MB (μg/L): 1.27±0.15 vs. 0.52±0.15, all P < 0.05]. HE staining showed that the myocardial striations of the rats in the normal control group were clear and complete, with normal morphology and orderly arrangement of cardiac cells. However in the sepsis groups, myocardial cells were swollen, ruptured and necrotic, and inflammatory cells were infiltrated, with myocardial fibers ruptured and necrosis dissolved, and the above pathological manifestations gradually increased with the extension of the model making time. Conclusion High-resolution ultrasound can evaluate the cardiac function of CLP induced sepsis rat model more comprehensive, and the consequence of evaluation index is consistent with the expression level of myocardial enzyme and histopathologic manifestations.

Experimental study of cardiac function by high-resolution ultrasound in sepsis rats with cecal ligation and puncture / 中华危重病急救医学

Objective@#To evaluate the cardiac function of cecal ligation and puncture (CLP) induced sepsis rats with high-resolution ultrasound.@*Methods@#According to the method of random number table, 48 adult male Sprague-Dawley (SD) rats were randomly divided into normal control group and sepsis 6, 12, 24, 30, 48 hours groups, with 8 rats in each group. The sepsis model was produced by CLP, and the rats in the normal control group were only anesthetized and resuscitated. The general situation after modeling in each group was observed, and the left ventricular function was assessed by high-resolution echocardiography at all the time points. The abdominal aorta blood of rats was collected, and the serum levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and MB isoenzyme of creatine kinase (CK-MB) were determined by enzyme-linked immunosorbent assay (ELISA). The myocardial tissue was harvested, and the pathological changes in myocardial tissue were observed by hematoxylin-eosin (HE) staining.@*Results@#The rats challenged to CLP displayed symptoms of sepsis, such as depression, ruffled fur, decreased diet and activity, and the symptoms became more obvious with the extension of time. High-resolution echocardiography could clearly show the structure of left ventricle in each group and obtain satisfactory M-mode echocardiography of left ventricle. The heart rate (HR) of rats in all sepsis groups was elevated with the increase in model time as measured by high-resolution ultrasound, and it was significantly higher than that in the normal control group at 12, 24, 30 hours (bpm: 359.66±23.33, 361.35±12.85, 392.67±11.33 vs. 306.24±29.79, all P < 0.05). Stroke volume (SV) and cardiac output (CO) in sepsis rats were decreased with the increase in model time, while left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) were increased first and then decreased, and SV and LVEF in sepsis 48 hours group were significantly lower than those in the normal control group [SV (μL): 78.43±17.52 vs. 122.61±15.88, LVEF: 0.763±0.018 vs. 0.902±0.011, both P < 0.05]. Left ventricular weight (LVW) in all sepsis groups was increased to different degrees as compared with that in the normal control group, as well as the left ventricular anterior and posterior wall thickness increased in diastole and systole. Compared with the normal control group, the left ventricular posterior wall thickness was increased significantly at the end of diastolic and systolic period in the sepsis 12 hours group, and the left ventricular anterior wall thickness was also increased significantly at the end of diastolic period in the sepsis 48 hours group. The serum levels of TNF-α, IL-1β and CK-MB in sepsis rats were increased first and then decreased with the extension of model making time. The above parameters in the sepsis 48 hours group were still significantly higher than those in the normal control group [TNF-α (ng/L): 61.59±3.99 vs. 16.87±4.89, IL-1β (ng/L): 255.03±13.23 vs. 119.59±10.43, CK-MB (μg/L): 1.27±0.15 vs. 0.52±0.15, all P < 0.05]. HE staining showed that the myocardial striations of the rats in the normal control group were clear and complete, with normal morphology and orderly arrangement of cardiac cells. However in the sepsis groups, myocardial cells were swollen, ruptured and necrotic, and inflammatory cells were infiltrated, with myocardial fibers ruptured and necrosis dissolved, and the above pathological manifestations gradually increased with the extension of the model making time.@*Conclusion@#High-resolution ultrasound can evaluate the cardiac function of CLP induced sepsis rat model more comprehensive, and the consequence of evaluation index is consistent with the expression level of myocardial enzyme and histopathologic manifestations.

Sodium tanshinone IIA sulfonate attenuates cardiac dysfunction and improves survival of rats with cecal ligation and puncture-induced sepsis / 中国天然药物

Cardiac dysfunction, a common consequence of sepsis, is the major contribution to morbidity and mortality in patients. Sodium tanshinone IIA sulfonate (STS) is a water-soluble derivative of Tanshinone IIA (TA), a main active component of Salvia miltiorrhiza Bunge, which has been widely used in China for the treatment of cardiovascular and cerebral system diseases. In the present study, the effect of STS on sepsis-induced cardiac dysfunction was investigated and its effect on survival rate of rats with sepsis was also evaluated. STS treatment could significantly decrease the serum levels of C-reactive protein (CRP), procalcitonin (PCT), cardiac troponin I (cTn-I), cardiac troponin T (cTn-T), and brain natriuretic peptide (BNP) in cecal ligation and puncture (CLP)-induced) septic rats and improve left ventricular function, particularly at 48 and 72 h after CLP. As the pathogenesis of septic myocardial dysfunction is attributable to dysregulated systemic inflammatory responses, several key cytokines, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-10 (IL-10) and high mobility group protein B1 (HMGB1), were detected to reveal the possible mechanism of attenuation of septic myocardial dysfunction after being treated by STS. Our study showed that STS, especially at a high dose (15 mg·kg), could efficiently suppress inflammatory responses in myocardium and reduce myocardial necrosis through markedly reducing production of myocardial TNF-α, IL-6 and HMGB1. STS significantly improved the 18-day survival rate of rats with sepsis from 0% to 30% (P < 0.05). Therefore, STS could suppress inflammatory responses and improve left ventricular function in rats with sepsis, suggesting that it may be developed for the treatment of sepsis.

Accelerated Autophagy of Cecal Ligation and Puncture-Induced Myocardial Dysfunction and Its Correlation with Mammalian Target of Rapamycin Pathway in Rats / 中华医学杂志(英文版)

<p><b>Background</b>Recent studies have indicated that autophagy is involved in sepsis-induced myocardial dysfunction. This study aimed to investigate the change of autophagy in cecal ligation and puncture (CLP)-induced myocardium dysfunction and its relationship with mammalian target of rapamycin (mTOR) pathway.</p><p><b>Methods</b>Totally, 12 rats were randomly divided into CLP group or sham-operated (SHAM) group. Cardiac tissues were harvested 18 h after CLP or sham operation. Pathology was detected by hematoxylin and eosin staining, cardiac functions by echocardiography, distribution of microtubule-associated protein light chain 3 type II (LC3II) by immunohistochemical staining, and autophagic vacuoles by transmission electron microscopy. Moreover, phosphorylation of mTOR (p-mTOR), phosphorylation of S6 kinase-1 (PS6K1), and LC3II and p62 expression were measured by western blotting. Pearson's correlation coefficient was used to analyze the correlation of two parameters.</p><p><b>Results</b>The results by pathology and echocardiography revealed that there was obvious myocardial injury in CLP rats (left ventricle ejection fraction: SHAM 0.76 ± 0.06 vs. CLP 0.59 ± 0.11, P < 0.01; fractional shortening: SHAM 0.51 ± 0.09 vs. CLP 0.37 ± 0.06, P < 0.05). We also found that the autophagy process was elevated by CLP, the ratio of LC3II/LC3I was increased (P < 0.05) while the expression of p62 was decreased (P < 0.05) in the CLP rats, and there were also more autophagosomes and autolysosomes in the CLP rats. Furthermore, the mTOR pathway in CLP myocardium was inhibited when compared with the sham-operated rats; p-mTOR (P < 0.01) and PS6K1 (P < 0.05) were both significantly suppressed following CLP challenge. Interestingly, we found that the mTOR pathway was closely correlated with the autophagy processes. In our study, while p-mTOR in the myocardium was significantly correlated with p62 (r = 0.66, P = 0.02), PS6K1 was significantly positively correlated with p62 (r = 0.70, P = 0.01) and negatively correlated with LC3II (r = -0.71, P = 0.01).</p><p><b>Conclusions</b>The autophagy process in the myocardium was accelerated in CLP rats, which was closely correlated with the inhibition of the mTOR pathway.</p>

Sodium tanshinone IIA sulfonate attenuates cardiac dysfunction and improves survival of rats with cecal ligation and puncture-induced sepsis / 中国天然药物

Cardiac dysfunction, a common consequence of sepsis, is the major contribution to morbidity and mortality in patients. Sodium tanshinone IIA sulfonate (STS) is a water-soluble derivative of Tanshinone IIA (TA), a main active component of Salvia miltiorrhiza Bunge, which has been widely used in China for the treatment of cardiovascular and cerebral system diseases. In the present study, the effect of STS on sepsis-induced cardiac dysfunction was investigated and its effect on survival rate of rats with sepsis was also evaluated. STS treatment could significantly decrease the serum levels of C-reactive protein (CRP), procalcitonin (PCT), cardiac troponin I (cTn-I), cardiac troponin T (cTn-T), and brain natriuretic peptide (BNP) in cecal ligation and puncture (CLP)-induced) septic rats and improve left ventricular function, particularly at 48 and 72 h after CLP. As the pathogenesis of septic myocardial dysfunction is attributable to dysregulated systemic inflammatory responses, several key cytokines, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-10 (IL-10) and high mobility group protein B1 (HMGB1), were detected to reveal the possible mechanism of attenuation of septic myocardial dysfunction after being treated by STS. Our study showed that STS, especially at a high dose (15 mg·kg), could efficiently suppress inflammatory responses in myocardium and reduce myocardial necrosis through markedly reducing production of myocardial TNF-α, IL-6 and HMGB1. STS significantly improved the 18-day survival rate of rats with sepsis from 0% to 30% (P < 0.05). Therefore, STS could suppress inflammatory responses and improve left ventricular function in rats with sepsis, suggesting that it may be developed for the treatment of sepsis.

Protective Effect of Shen Fu Injection on Cardiac Function in Sepsis Rats Through p38MAPK Pathway / 广州中医药大学学报

Objective To investigate the protective effect of Shen Fu Injection (SFI) on cardiac function in sepsis rats and to explore the possible mechanism.Methods Forty SD male rats were randomly divided into 4 groups,namely normal control group,sham operation group,model group,SFI group.The sepsis model was established by cecal ligation and puncture (CLP).Thirty-six hours later,the arterial blood and left ventricular myocardium tissues were collected,and then the serum levels of tumor necrosis factor(TNF)-α and interleukin(IL)-1 were detected and the levels ofphosphorylated p38-mitogen-activated protein kinase (p-p38MAPK) and p38-mitogenactivated protein kinase (p38MAPK) in the supernatant of myocardial homogenate were detected.Results Thirty-six hours after modeling,left ventricular ejection fraction (LVEF) and left ventricular fractional shortening(LVFS) of the rats in the model group were significantly lower than those in the sham operation group (P ＜ 0.05).The heart function in SFI group was much improved compared with the model group (P ＜ 0.05).The serum TNF-α and IL-1 levels as well as p-p38/p38MAPK level in the supernatant of myocardial tissue of SFI group were lower than those in the model group (P ＜ 0.05).There were no significant differences of the above indexes between the sham operation group and the normal control group (P ＞ 0.05).Conclusion SFI has protective effect against sepsis myocardial injury.The mechanism may be related with the inhibition of p38MAPK phosphorylation in the myocardium,thereby reducing the release ofinflammatory cytokines in the pathway.

The correlation between the soluble triggering receptor expressed on myeloid cells-1 and the janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway in rats with abdominal sepsis / 中华急诊医学杂志

Objective To investigate the correlation between the soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) and the janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway in rats with abdominal sepsis.Methods Using a sepsis model produced by cecal ligation and puncture (CLP),Wistar rats were randomly (random number) divided into normal control group (n =6),sham-operated group (n =24,) CLP group (n =48),AG490 (JAK2 inhibitor) treatment group (n =48) and rapamycin (RPM,STAT3 inhibitor) treatment group (n =48).At different intervals,the rats in each group were sacrificed,then the peripheral blood cells were harvested to detect the percent of CD4 + CD25 + Treg cells in CD4 + cells by flow cytometry.Meanwhile,mRNA of sTREM-1 from the tissue samples of the liver was also measured by real-time reverse transcription-polymerase chain reaction (RT-PCR).Results Compared with the normal control group and the sham-operated group,expression of sTREM-1 in the CLP group was significantly higher,and it showed a gradually increased tendency over time.At 6 and 24 hours,there were no significant differences in the expressions of sTREM-1 between the AG490 group (1.572 ± 0.051,2.063 ± 0.025,respectively) and the CLP group (1.592 ±0.036,2.082 ±0.021,respectively).But the expression of sTREM-lin the AG490 group (2.522 ± 0.083,3.153 ± 0.021,respectively) was lower than those in the CLP group (2.592 ±0.055,3.204 ±0.013,respectively) during 48 and 72 hours.In addition,there was no significant difference in the expression of sTREM-1 between the RPM group (1.581 ± 0.017) and the CLP group (1.592 ±0.036) at 6 hours.And the expression of sTREM-1in the RPM group (1.486 ±0.019,1.263 0.011,1.115 ± 0.022,respectively) was significantly lower than those in the CLP group (2.082 ± 0.021,2.592 ±0.055,3.204 ± 0.013,respectively) during 24 to 72 hours.Conclusions These data proved that blocking JAK/STAT pathway could inhibit the expression of sTREM-1 and decelarate the progress of inflammatory reaction in rats with abdominal sepsis.

Effect of excretory/secretory protein of Trichinella spiralis adult worm on CLP-induced sepsis in mice / 中国血吸虫病防治杂志

Objective To observe the effect of excretory/secretory products from Trichinella spiralis adult worms(AES)on cecal ligation and puncture(CLP)?induced sepsis in mice. Methods Forty?eight BALB/c mice were randomly divided into 3 groups:a sham operation group(PBS+sham group,Group A),a CLP?induced sepsis group(PBS+CLP group,Group B)and an AES treatment group(AES+ CLP group,Group C). The mice of each group were intraperitoneally injected with 25 μg of AES or PBS only as a control in a total volume of 200μl. Eight mice from each group were selected randomly for survival analy?sis of 96 hours. The other 8 mice in each group were observed for pathological changes in the lung,liver and kidney tissues by HE staining 12 h after CLP,and then determined for the detection of cytokines including TNF?α,IL?1β,IL?6,IL?10 and TGF? βin the sera by ELISA. Results The difference among the survival rates of mice in the 3 groups was statistically significant (χ2=21.16,P<0.05). Compared to Group A(100%),the survival rate of mice in Group B(0)decreased significantly(P<0.05),and also the pathological damage degrees in the lung,liver and kidney tissues of the mice in Group B increased signifi?cantly after CLP. Compared with the mice in group B,the survival rate of those in Group C(70%)increased significantly(P<0.05),and the pathological damage degrees in the lung,liver and kidney tissues of the mice in Group C decreased significantly after the treatment with AES. The differences among the levels of pro?inflammatory cytokines TNF?α(F=27.11,P<0.05),IL?1β(F=18.75,P<0.05)and IL?6(F=100.93,P<0.05)in the sera of the mice in the three groups were statistically signifi?cant. Compared with the mice in Group A,the levels of the 3 cytokines of those in Group B increased significantly(all P <0.05). However,after the treatment with AES,the levels of the pro?inflammatory cytokines of those in Group C decreased signifi?cantly(all P<0.05). The differences among the levels of immunoregulatory cytokines IL?10(F=10.88,P<0.05)and TGF?β(F=11.37,P<0.05)in the sera of the mice in the three groups were also statistically significant. Compared with the mice in Group B,the levels of IL?10 and TGF?β of those in Group C were higher after treatment with AES(both P<0.05). Conclu?sion T. spiralis AES has a therapeutic potential for alleviating sepsis induced by CLP in mice.

The Effect of Bortezomib on Expression of Inflammatory Cytokines and Survival in a Murine Sepsis Model Induced by Cecal Ligation and Puncture

PURPOSE: Although the proteasome inhibitor known as bortezomib can modulate the inflammatory process through the nuclear factor-kappa B signaling pathway, the immunomodulatory effect of pre-incubated bortezomib has not been fully evaluated for inflammation by infectious agents. Therefore, we evaluated the effect of bortezomib on the expression of inflammatory cytokines and mediators in macrophage cell lines and on survival in a murine peritonitis sepsis model. MATERIALS AND METHODS: Bortezomib was applied 1 hr before lipopolysaccharide (LPS) stimulation in RAW 264.7 cells. The cecal ligation and puncture (CLP) experiments were performed in C57BL/6J mice. RESULTS: Pre-incubation with bortezomib (25 nM or 50 nM) prior to LPS (50 ng/mL or 100 ng/mL) stimulation significantly recovered the number of viable RAW 264.7 cells compared to those samples without pre-incubation. Bortezomib decreased various inflammatory cytokines as well as nitric oxide production in LPS-stimulated cells. The 7-day survival rate in mice that had received bortezomib at 0.01 mg/kg concentration 1 hr prior to CLP was significantly higher than in the mice that had only received a normal saline solution of 1 mL 1 hr prior to CLP. In addition, the administration of bortezomib at 0.01 mg/kg concentration 1 hr before CLP resulted in a significant decrease in inflammation of the lung parenchyma. Collectively, pretreatment with bortezomib showed an increase in the survival rate and changes in the levels of inflammatory mediators. CONCLUSION: These results support the possibility of pretreatment with bortezomib as a new therapeutic target for the treatment of overwhelming inflammation, which is a characteristic of severe sepsis.

The diagnostic value of urinary neutrophil gelatinase-associated lipocalin (NGAL) to the acute kidney injured septic rats / 中华急诊医学杂志

Objective ①Observing urinary neutrophil gelatinase-associated lipocalin (uNGAL)'s concentration variation under the intervention of sepsis; ②Evaluatingu NGAL' s diagnostic value for early acute kidney injury (AKI).Method Fifty-six SD (Sprague Dawley) rats were randomly (random number) divided into four groups,including 16 rats in model group (CLG),16 rats in Xuebijing group (XBG),16 rats in Huangqi and Chaihu injection jointly applied group (HCG),and 8 rats in sham operation group (SOG).The septic models in CLG group,HCG group and XBG group were established by cecal ligation and puncture (CLP).Then,the rats in HCG group was treated with intraperitoneal injectionby Huangqi and Chaihu injections; the XBG group was treated with intravenous injection by Xuebijing injection; the SOG group was treated with open surgery without CLP.After the CLP,serial urine and serum samples were obtained at baseline (just prior to operation),6 h,12 h,18 h,24 h,36 h,48 h,and 72 h,and were measured by sCr,uCr,uNa,and uNGAL.The line graph of uNGAL' s concentration variation was plotted,based on the time.Diagnostic characteristics of urinary NGAL in predicting AKI were assessed by calculating the area under the receiver operating characteristic curve (AUC).Results After the CLP,the uNGAL of sepsis model rats increased quickly within 6 hours.The time points of each group model reaching their peak were 6 hours after CLP in CLG groupand 24 hours after CLP in HCG group and XBG group.These groups' uNGAL all decreased quickly after the peak.The cuNGAL of sepsis model rats was increased quickly within 6 hours after CLP,reached its peak at 24 hours after CLP.In CLG group,the line graphs of uNGAL or cuNGAL were almost overlapped.There is little difference in the concentration of uNGAL or cuNGAL at each time point (uNGAL:6h,t=0.691; 12h,t=1.627; 18 h,t=0.511,cuNGAL:6h,t =0.371 ; 12 h,t =0.474; 18 h,t =-1.187.Statistical significance of all above value was P ＞0.05).InXBG group,the line graph of uNGAL and cuNGAL were not overlapped,but difference between uNGAL and cuNGAL concentration at each time point was not significant (uNGAL:6 h,t =1.222 ; 12 h,t =1.178 ; 18h,t=1.272; 24h,t=0.918; 36h,t =0.442.cuNGAL:6 h,t =1.482; 12 h,t =1.314; 18 h,t=1.280; 24 h,t =0.280; 36 h,t =0.467.Statistical significance of all above value was P ＞ 0.05).In HCG group,uNGAL of AKI rats were higher than non-AKI rats at each time points since 6 hours later (6 h,t =2.351,P＜0.05; 12h,t=3.086,P＜0.01; 18h,t=2.535,P＜0.05;24h,t=2.150,P＜0.05;36h,t =2.485,P ＜ 0.05),The average cuNGAL of AKI rats and non-AKI rats have statistical significance at 6h,18 h,and 24 h (6 h,t=3.013.P＜0.01; 18 h,t =4.804,P＜0.01; 24 h,t=2.682,P＜0.05).At 6 h,Uout can increase cuNGAL' s ability of predicting AKI' s occurrence in 24 hours (AUC increased from 0.839 to 0.900,P ＜ 0.05).Conclusions The intervention to the sepsis rats have influence on the secretion volume and secretion sequence of NGAL in rat urine.uNGAL and cuNGAL are good predictor of AKI occurrence in sepsis rats.

Effect of compound hypertonic saline solution on septic rats / 中华危重病急救医学

Objective To study the effect of compound hypertonic saline solution (HSD) on sepsis.Methods 133 male Wistar rats were divided into four groups,sham operation group (n =15),cecal ligation and puncture (CLP)group (n =45),CLP plus normal saline (NS) group (n =45),and CLP plus HSD group (n =28).A rat model of sepsis was reproduced by CLP,and the rats in sham operation group received celiotomy without ligation and puncture.All rats in four groups received subcutaneous injection of 30 mL/kg 0.9％ sodium chloride after laparotomy.The rats in CLP plus NS group and CLP plus HSD group received infusion of 5 mL/kg 0.9％ sodium chloride or 7.5％ sodium chloride/6％ dextran post CLP via jugular vein for 3 hours,with the infusion rate of 0.4 mL·kg-1·min-1.The survival rate of each group was observed 9 hours and 18 hours after laparotomy.Mean arterial pressure (MAP) at 0,9,18 hours were monitored.Blood specimens were collected from all rats 0,9 and 18 hours after laparotomy,respectively,for measurement of the plasma levels of tumor necrosis factor-α (TNF-α),interleukin-1β (IL-1β),and procalcitonin (PCT).The rats were all sacrificed,and their lung tissues were harvested for the neutrophil count in bronchoalveolar lavage fluid (BALF),myeloperoxidase (MPO) activity in lung tissue,wet/dry weight ratio (W/D) of lung,and pathological changes in lung tissue.Results There was no death in the sham operation group.The survival rates at 9 hours and 18 hours were 62.2％ and 31.1％ in the CLP group,57.8％ and 35.6％ in the CLP plus NS group,85.7％ and 64.3％ in the CLP plus HSD group,and they were all significantly higher compared with those of the CLP group and the CLP plus NS group (P ＜ 0.05 or P ＜ 0.01).MAP levels in the CLP group and the CLP plus NS group were significantly lower than those in sham operation group,and the plasma levels of TNF-α,IL-1β and PCT were significantly higher compared with those of sham operation group,while there was no difference between CLP group and the CLP plus NS group.MAP and the plasma levels of TNF-α,IL-1β and PCT in the CLP plus HSD group were significantly improved compared with those of the CLP plus NS group at 9 hours and 18 hours [MAP (mmHg,1 mmHg =0.133 kPa) at 9 hours:102±5 vs.94±6,18 hours:90±2 vs.72±3; TNF-α (ng/L) at 9 hours:284.19±57.18 vs.329.67±45.79,18 hours:263.46±42.58 vs.349.68±52.40; IL-1β (ng/L) at 9 hours:219.28±39.21 vs.263.47±32.36,18 hours:195.98±39.06 vs.250.10±41.57; PCT (μg/L) at 9 hours:2.32±0.37 vs.4.52±0.75,18 hours:2.89±0.62 vs.5.02±0.84; P ＜ 0.05 or P ＜ 0.01].The ratio of neutrophils in BALF,MPO activity and lung W/D at 18 hours in the CLP group and the CLP plus NS group were significantly higher than those of the sham operation group,while they were all significantly lower in the CLP plus HSD group than those of the CLP group and the CLP plus NS group [ratio of neutrophils in BALF:0.094±0.019 vs.0.148±0.062,0.151 ±0.055; MPO (U/g):1.19±0.45 vs.2.31 ±0.79,2.64±0.69; lung W/D ratio:4.02 ± 0.63 vs.5.14 ± 0.59,5.12 ± 0.83,all P ＜ 0.05].Under light microscope,no pathobiological changes were found in sham operation group.The lung tissues in the CLP group and the CLP plus NS group showed congestion,edema,infiltrating inflammatory changes,while the inflammatory changes in the lung tissue in the CLP plus HSD group were significantly alleviated.Conclusion HSD can obviously ameliorate the circulatory failure in septic rats,alleviate immune disturbance and acute lung injury,and improve the survival rate of rats with sepsis.

Berberine Prevents Intestinal Mucosal Barrier Damage During Early Phase of Sepsis in Rat through the Toll-Like Receptors Signaling Pathway

Our previous study has shown berberine prevents damage to the intestinal mucosal barrier during early phase of sepsis in rat through mechanisms independent of the NOD-like receptors signaling pathway. In this study, we explored the regulatory effects of berberine on Toll-like receptors during the intestinal mucosal damaging process in rats. Male Sprague-Dawlay (SD) rats were treated with berberine for 5 d before undergoing cecal ligation and puncture (CLP) to induce polymicrobial sepsis. The expression of Toll-like receptor 2 (TLR 2), TLR 4, TLR 9, the activity of nuclear factor-kappa B (NF-kappaB), the levels of selected cytokines and chemokines, percentage of cell death in intestinal epithelial cells, and mucosal permeability were investigated at 0, 2, 6, 12 and 24 h after CLP. Results showed that the tumor necrosis factor-alpha (TNF-alpha ) and interleukin-6 (IL-6) level were significantly lower in berberine-treated rats compared to the control animals. Conversely, the expression level of tight junction proteins, percentage of cell death in intestinal epithelial cells and the mucosal permeability were significantly higher in berberine-treated rats. The mRNA expression of TLR 2, TLR 4, and TLR 9 were significantly affected by berberine treatment. Our results indicate that pretreatment with berberine attenuates tissue injury and protects the intestinal mucosal barrier in early phase of sepsis and this may possibly have been mediated through the TLRs pathway.

Therapeutic effects of compound hypertonic saline on rats with sepsis

Sepsis is one of the major causes of death and is the biggest obstacle preventing improvement of the success rate in curing critical illnesses. Currently, isotonic solutions are used in fluid resuscitation technique. Several studies have shown that hypertonic saline applied in hemorrhagic shock can rapidly increase the plasma osmotic pressure, facilitate the rapid return of interstitial fluid into the blood vessels, and restore the effective circulating blood volume. Here, we established a rat model of sepsis by using the cecal ligation and puncture approach. We found that intravenous injection of hypertonic saline dextran (7.5% NaCl/6% dextran) after cecal ligation and puncture can improve circulatory failure at the onset of sepsis. We found that the levels of tumor necrosis factor-α, interleukin-1β, interleukin-6 and intracellular adhesion molecule 1 levels in the lung tissue of cecal ligation and puncture rats treated with hypertonic saline dextran were significantly lower than the corresponding levels in the control group. We inferred that hypertonic saline dextran has a positive immunoregulatory effect and inhibits the overexpression of the inflammatory response in the treatment of sepsis. The percentage of neutrophils, lung myeloperoxidase activity, wet to dry weight ratio of lung tissues, histopathological changes in lung tissues, and indicators of arterial blood gas analysis was significantly better in the hypertonic saline dextran-treated group than in the other groups in this study. Hypertonic saline dextran-treated rats had significantly improved survival rates at 9 and 18 h compared to the control group. Our results suggest that hypertonic saline dextran plays a protective role in acute lung injury caused after cecal ligation and puncture. In conclusion, hypertonic/hyperoncotic solutions have beneficial therapeutic effects in the treatment of an animal model of sepsis.