Pulmonary delivery of siRNA against acute lung injury/acute respiratory distress syndrome

The use of small interfering RNAs (siRNAs) has been under investigation for the treatment of several unmet medical needs, including acute lung injury/acute respiratory distress syndrome (ALI/ARDS) wherein siRNA may be implemented to modify the expression of pro-inflammatory cytokines and chemokines at the mRNA level. The properties such as clear anatomy, accessibility, and relatively low enzyme activity make the lung a good target for local siRNA therapy. However, the translation of siRNA is restricted by the inefficient delivery of siRNA therapeutics to the target cells due to the properties of naked siRNA. Thus, this review will focus on the various delivery systems that can be used and the different barriers that need to be surmounted for the development of stable inhalable siRNA formulations for human use before siRNA therapeutics for ALI/ARDS become available in the clinic.

The study of using cordyceps-astragalus-salvia miltiorrhiza to treat acute lung injury induced by paraquat poisoning in rats / 中华劳动卫生职业病杂志

Objective@#To study the therapy of cordyceps-astragalus-salvia miltiorrhiza in treating acute lung injury and pulmonary interstitial fibrosis induced by paraquat poisoning.@*Methods@#All 120 adult Wister male rats were randomly assigned to three groups, the paraquat poisoning group (rats were intragastric administration paraquat 50 mg/kg body weight once at the beginning) , the cordyceps-astragalus-salvia miltiorrhiza therapy group (rats were given cordyceps-astragalus-salvia miltiorrhiza 90 mg/kg body weight intragastric administration half an hour after paraquat was given, then the same dose was given once a day) ; control group (rats were intragastric administration with physiological saline) . At 7th, 14th, 21st, and 28th day rats were sacrificed postanesthetic respectively after paraquat exposure, sample of lung tissue, bronchoalveolar lavage (BAL) , and venous blood were collected. GSH, SOD, TNF-α, TGF-β1, and HYP in plasma, bronchoalveolar lavage (BAL) , and the lung homogenates were determined. Optical microscope was performed to examine pathological changes in lung.@*Results@#Each experimental time point paraquat group and the treatment group rats serum SOD content significantly lower than the control group (P<0.05) . Each experimental time point the treatment group rats serum SOD levels increased significantly than that of paraquat group (P<0.05) . Each experimental time point paraquat group rats serum GSH content significantly lower than that of the control group (P<0.05) . Treatment group rats 7 days time GSH content significantly lower than that of the control group (P<0.05) . Treatment group 21 days, 28 days GSH content was increased significantly than that of the paraquat group (P<0.05) . Each experimental time point paraquat group rats alveolar lavage SOD content was significantly lower than that of the control group (P<0.05) . Treatment group 7 days, 14 days time SOD content was significantly lower than that of the control group (P<0.05) , Treatment group 21 days, 28 days SOD content was increased significantly than that of the paraquat group (P<0.05) . Each experimental time point paraquat group and the treatment group rats alveolar lavage GSH content significantly were lower than that of the control group (P<0.05) . Treatment group days 14 and 21 days, 28 days GSH content was increased significantly than that of the paraquat group (P<0.05) . Each experimental time point paraquat group rats alveolar lavage TNF α levels was higher than that of the control group (P<0.05) . Treatment group 7 days, 14 days the rat alveolar lavage TNF α levels was higher than that of the control group (P<0.05) . Treatment group 21 days, 28 days TNF α content significantly was decreased than that of paraquat group (P<0.05) . Paraquat group days 14 and 21 days, 28 days HYP content was significantly higher than that of control group (P<0.05) . Treatment group 21 days HYP content was significantly higher than that of control group (P<0.05) . Treatment group 28 days time HYP content in lung tissue of rats was significantly decreased than that of the paraquat group (P<0.05) . Each experimental time point paraquat group rat lung tissue (tissue homogenate) TGF-β1 content was higher than that of the control group, the difference was statistically significant (P<0.05) . Under optical microscope, the tissue damage of lung was aggravated, and reduced after cordyceps-astragalus-salvia miltiorrhiza was administrated.@*Conclusion@#Cordyceps-astragalus-salvia miltiorrhiza can reduce inflammation factor releasing, and relieve lung injury. It has therapeutic effect on lung injury induced by paraquat poisoning.

Expression of microRNA -30e in sepsis - induced acute lung injury rats and its correlation with the levels of inflammatory cytokines / 中华实用儿科临床杂志

Objective To investigate the differential expression of microRNA - 30e in sepsis - induced acute lung injury(ALI)and its correlation with interleukin(IL)- 1β and tumor necrosis factor(TNF)- α from two aspects of in vivo and in vitro. Methods Thirty SD male rats were randomly divided into 5 groups:normal control group,3 - hour sepsis group,6 - hour sepsis group,12 - hour sepsis group and 24 - hour sepsis group in equal number. Sepsis - in-duced ALI model was induced by intraperitoneal injection of lipopolysaccharide(LPS,10 mg/ kg). The rat alveolar mac-rophages NR8383 were divided into blank control group and LPS(1 mg/ L)stimulated 3,6,12,24 hour groups. Inverse transcription - polymerase chain reaction was used to assay the production changes of IL - 1β,TNF - α and miRNA - 30e in lungs and cells. The injury of lung tissue was evaluated through histopathology. Results The levels of IL - 1β and TNF - α in lung tissues of rats in sepsis groups were obviously up - regulated when compared with those in normal control groups(all P ﹤ 0. 01). The lung tissue hematoxylin - eosin staining indicated ALI in the sepsis group. The relative expression of miR - 30e in rat lung tissue in sepsis 3,6,12,24 hour groups were respectively 0. 26 ± 0. 02, 0. 41 ± 0. 08,0. 29 ± 0. 05 and 0. 18 ± 0. 05,which were significantly lower than those in normal control group(1. 23 ± 0. 24,all P ﹤ 0. 01). The levels of IL - 1β and TNF - α in LPS stimulated NR8383 cells at different time points were obviously up - regulated when compared with those in blank control groups(all P ﹤ 0. 01). The relative expression of miR - 30e in LPS stimulated 3,6,12,24 hour groups were respectively 0. 27 ± 0. 04,0. 55 ± 0. 05,0. 65 ± 0. 02 and 0. 41 ± 0. 10,which were significantly lower than those in blank control group(1. 17 ± 0. 21,all P ﹤ 0. 01). The expres-sion of miR - 30e in lung tissues of groups showed significantly negative correlations with those of IL - 1β and TNF - α(IL - 1β:r = - 0. 417,P = 0. 022;TNF - α:r = - 0. 437,P = 0. 016). The expression of miR - 30e in LPS stimulated NR8383 cells of groups also showed significantly negative correlations with those of IL - 1β and TNF - α(IL - 1β :r =- 0. 713,P = 0. 003;TNF - α:r = - 0. 712,P = 0. 002). Conclusions The expression level of miR - 30e was signifi-cantly down - regulated in sepsis - induced ALI,and had a significantly negative correlation with IL - 1β and TNF - α, which may be used as a new biomarker of diagnostic,prognosis evaluation and therapy of sepsis - induced ALI.

The impact of relevant factors in mechanical ventilation on intra-abdominal pressure in patients with ALI/ARDS / 中华急诊医学杂志

Objective To investigate the impact of relevant factors in mechanical ventilation on intraabdominal pressure in patients with ALI/ARDS by continuous monitoring of intra-abdominal pressure.Methods A total of 116 ALI/ARDS patients treated with mechanical ventilation in ICU were enrolled in this study.Intra-abdominal pressure (IAP) was recorded continuously.Meanwhile ventilator parameters, arterial blood gas analysis, hemodynamic variables, and as well as the levels of IL-4, IL-8 and TNF-α in blood and bronchial alveolar lavage fluid (BALF) were determined and recorded.The detection of risk factors for intra-abdomen hypertension (IAH) were carried out using multivariate stepwise logistic regression.ROC curve analysis used to estimate the diagnostic performance of these parameters for IAH.Results The oxygenation index (PaO2/FiO2) in patients with IAH after 2 hours' mechanical ventilation was significantly lower than that in patients with normal intra-abdomen pressure (IAP) (P ＜ 0.01);PEEP and RR in mechanical ventilation were higher in IAH group (P ＜ 0.01 or P =0.001);Mean artery pressure (MAP), ejection time percent (ET), stroke volume (SV), cardiac index (CI) were lower in IAH group than those in normal IAP group (P ＜ 0.01);the levels of IL-4, IL-8 and TNF-α in blood and bronchial alveolar lavage fluid were higher in IAH group than those in normal IAP group (P ＜ 0.01);IAH patients have a higher mortality on 28 d (Log rank test, P =0.023).Poor oxygenation index (PaO2/ FiO2) after 2 hours' ventilation, high PEEP setting, low MAP, ET, SV, CI and elevated IL-4 in the BALF were resulted in increasing risk of IAH for ARDS patients under mechanical ventilation support.Conclusions The monitoring of intra-abdominal pressure should be emphasized for ALI/ARDS patients when mechanical ventilation was employed.PaO2/FiO2, SV and IL-4 in BALF might be the independent risk factors of IAH.

CRRT at early stageon in patients with severe acute pancreatitis applied to preventing acute lung injury in patients with severe acute pancreatitis / 中国基层医药

Objective To investigate the effects of early continuous renal replacement thempy(CRRT)on acute lung injury and prognosis in severe acute pancreatitis (SAP)patients.Methods 46 SAP patients were divided into the two groups randomly:the control group and CRRT treatment group.The levels of IL-1β,IL-6,TNF-α,the APACHEⅡscore,oxygenation index,the incidence of acute lung injury(ALI)/acute respiratory distress syndrome (ARDS),ICU stay were compared between the two groups.Results The level of interleukin-6(IL-6)in the con-trol group was significantly higher than that in CRRT group in day 1(t=2.265,P0.05).Conclusion Early CRRT therapy can eliminate the IL-1β,IL-6 and TNF-αin SAP patients,which can improve the oxygenation index and reduce the incidences of ALI/ARDS,may provide more clinical benefits in the early phase of SAP.

The clinical significance of nitric oxide and endothelin-1 in exhaled breath condensate and serum of patients with acute lung injury/acute respiratory distress syndrome / 实用医学杂志

Objective To observe the level of the nitric oxide (NO) and endothelin-1 (ET-1) in the exhaled breath condensate(EBC)and serum of the patients with ALI /ARDS, and investigate its clinical significance. Methods The study group included 52 mechanical ventilation patients with ALI/ARDS in ICU , which were divided into the survival and death group, while 30 healthy volunteers were recruited as healthy control. EBC samples of the healthy control and the study group on the 1st day and 5st day were collected by EcoScreen condenser with the synchronous collection of the venous blood. The concentrations of NO and ET-1 in the EBC and serum were measured by EIA. Results The levels of NO and ET-1 in EBC and serum of the patients with ALI /ARDS were all significantly higher than those of the healthy control. After treatment , the levels of NO and ET-1 in EBC and serum of the patients all decreased significantly compared with before treatment. After treatment , The levels of NO in EBC and serum of the survival group were significantly lower than those of the death group. After treatment , the levels of ET-1 in serum of the survival group was significantly lower than that of the death group. Conclusions Detecting the levels of NO and ET-1 in the EBC and serum can reflect oxidative stress , inflammatory reaction and endothelial injury in lung of patients with ALI/ARDS.

Protective Effects of Ethanol Extracts of Calonyction Acculeatum Beans on Rats with Acute Lung Injury / 医药导报

Objective To investigate the protective effects of ethanol extract of calonyction acculeatum beans( CABE) on rats with acute lung injury ( ALI ) . Methods The ALI model was induced via intravenous injection with 5 mg · kg-1 lipopolysaccharide(LPS). The expression of nuclear factor-кB p65(NF-кB65) was determind by immunohistochemistry(IHC), and the content of interleukin-1β( IL-1β) in the lung tissue was detected by enzyme-linked immunosorbent assay ( ELISA ) . Meanwhile,lung tissue histopathology,the wet-dry weight ratio of lung and the activity of myeloperoxidase(MPO) in the lung tissues were observed. Results Compared with the model group, CABE lessened the lung injury, decreased IL-1β level, reduced the lung dry-wet weight ratio and activity of MPO,and down-regulated the expression of NF-кB/p65(P<0. 05). Conclusion CABE has remarkedly protective effect on ALI induced by LPS in rats. One of the mechanisms may be related to reducing the secretion of IL-1β and interfering with the activity of NF-кB.

The clinical effect of traditional Chinese medicine dialectical therapy for treatment of gastrointestinal dysfunction in patients with acute lung injury/acute respiratory distress syndrome undergoing mechanical ventilation / 中国中西医结合急救杂志

Objective To explore the clinical effect of traditional Chinese medicine (TCM) dialectical therapy for treatment of gastrointestinal dysfunction in patients with acute lung injury / acute respiratory distress syndrome(ALI/ARDS)undergoing mechanical ventilation. Methods A prospective,randomized controlled trial was conducted. Ninety-six ALI/ARDS patients admitted in intensive care unit(ICU)and treated with mechanical ventilation in Tianjin First Central Hospital were chosen and randomly divided into traditional Chinese medicine(TCM) group and conventional therapy group using a random number table,48 patients in each group. Conventional therapy alone was used in conventional therapy group,and TCM therapy of primarily using Dachengqi decoction combined with conventional therapy was applied in TCM group〔Dachengqi decoction was composed of mongolian milkvetch root 15 g, pilose asiabell toot 15 g,Chinese angelica 10 g,officinal magnolia bark 10 g,tangerine peel 10 g,immature tangerine fruit 10 g,peach seed 10 g,white peony root 12 g,red peony root 12 g,immature bitter orange 6 g,mongolian dandelion herb 30 g,radish seed(stir-fried)30 g,foxtail millet sprout 20 g,barley sprout 20 g,glauber salt 9 g (with water),rhubarb 10 g(added in water at last)〕,one dose orally taken daily for 28 days. The intra-abdominal pressure(IAP),gastrointestinal diseases in TCM symptom score and the incidence of gastrointestinal dysfunction were compared between the two groups before treatment and on the 3rd,6th and 8th day after treatment. Results There were no statistical significant differences in IAP and TCM symptom scores between the two groups before treatment (both P>0.05),but after treatment with the prolongation of therapeutic time the IAP and TCM symptom scores were decreased gradually compared with those before treatment,having reached the valley value on the 18th day and the changes in TCM group were more remarkable〔IAP(mmHg,1 mmHg=0.133 kPa):0.91±0.69 vs. 2.08±0.92, TCM symptom score:48.33±10.41 vs. 88.33±20.21,both P<0.05〕. In the TCM group,the incidences of the untoward symptoms and signs of gastrointestinal dysfunction such as bleeding of stress ulcer,toxic intestinal paralysis, abdominal distension,diarrhea and so on were lower than those in conventional therapy group〔stress ulcer bleeding:16.7%(8/48)vs. 39.6%(19/48),toxic intestinal paralysis:16.7%(8/48)vs. 43.8%(21/48),abdominal distension:10.4%(5/48)vs. 37.5%(18/48),diarrhea:6.3%(3/48)vs. 33.3%(16/48),all P<0.05〕. Conclusion Addition of TCM Dachengqi decoction on conventional treatment can effectively lower the incidence of gastrointestinal dysfunction in treatment of patients with ALI/ARDS undergoing mechanical ventilation.

Intestinal lymph drainage reduces lung tissue cell apoptosis of hemorrhagic shock rats / 中国基层医药

ObjectiveTo explore the effect of the intestinal lymph drainage on lung tissue cell apoptosis in rats with hemorrhagic shock after resuscitation,rich ALI intestinal lymphatic pathway theory.MethodsTUNEL method was used to determine the apoptosis of lung tissue cells,the brown nuclei were apoptotic cells.SABC was used to determine Bcl-2 and Bax protein expression.ResultsThe shock group and shock + drainage group lung tissue cell apoptosis rate were significantly higher than those in the sham operation group,but the shock + drainage group,the apoptosis of lung tissue cells was significantly lower than the shock group.Sham operation group showed Bcl-2,Bax protein of expression; In shock group,lung tissue cell Bcl-2 expression was significantly lower than the sham operation group,the Bax expression was significantly higher than that in the sham operation group; In shock + drainage group,lung tissue cells shored enhanced expression of Bcl-2,Bax expression was reduced,and the shock + drainage group lung tissue cell Bcl-2 expression was significantly higher than that in the shock group,the expression of Bax was significantly lower than the shock group.ConclusionThe excessive apoptosis of lung tissue cells was one of the mechanisms of lung injury after shock.Intestinal lymph drainage could reduce lung tissue cell apoptosis,the mechanism invdved the regulation of Bcl-2/Bax protein expression.

Application of nitric oxide in the therapy of respiratory diseases / 中国小儿急救医学

Nitric oxide (NO) played an important role in the pathogenesis of many diseases. It selectively dilates the pulmonary vasculare, combats pulmonary hypertension associated with hypoxemia, improves oxygen. At the same time, it could relaxe bronchial smooth muscle, kill pathogens and have anti-inflammatory effect,etc. Inhaled nitric oxide has important significance in the treatment of respiratory diseases.

The effect of EVLW in fluid managemeent on sepsis ALI/ARDS / 中华急诊医学杂志

Objective The management of fluid infusion is crucial in severe sepsis/septic shock patients.The correlation of extravascular lung water index(EVLWI) versus oxygenation index ( PaO2/FiO2 ) and EVLWI versus intrathoracic blood volume index(ITBVI) were analysed in this present study. Method Totally 24 patients,admitted to the Intensive Care Unit of Second Affiliated Hospital of Zhejiang University, College of Medicine and diagnosed as severe sepsis/septic shock with acute lung injury and/or acute respiratory distress syndrome,were enrolled. ITBVI and EVLWI were detected with PiCCO technique. Correlation of EVLWI and PaO2/FiO2, ITBVI and EVLWI were analysed,respectively. Simple correlation and simple linear regression were used for statistical analysis. Results Significant negative correlation was found of EVLWI and PaO2/FiO2 ( r = - 0. 45, P ＜ 0.01).EVLWT = 14 mL/kg was defined as the cutoff value for the subgroup analysis. No correlation was found between EVLWI and PaO2/FiO2 in the subgroup with EVLWI≤ 14 mL/kg ( r = 0. 12, P = 0.243), but in the subgroup with EVLWI ＞ 14 mL/kg, significant negative correlation was found ( r = - 0. 47, P ＜ 0. 01 ). When EVLWI was higher than 14 mL/kg,EVLW should be decreased to improve oxygenation and other aspects should be taken into account. No significant correlation was found between ITBVI and EVLWI. A ITBVI value 1000 mL/m2 was also defined as the cutoff value for the subgroup analysis. No significant correlation was found in the subgroup with ITBVI≤ 1000 mL/m2( r = 0.13, P = 0.17), while significant positive correlation was found in the subgroup with ITBVI ＞ 1000 mL/m2. This result suggested that in patients of severe sepsis/septic shock with ALI/ARDS, when the blood volume is high, ITBV should be decreased to improve the oxygenation,however,it is not useful in the situation of high pulmonary vascular permeability. Conclusions Extravascular lung water has a important role in the fluid management in patients of severe sepsis/septic shock with ALI/ARDS.

The change of Bax/Bcl-2 on endotoxin-induced acute lung injury / 中国基层医药

Objective To observe the change of Bax/Bcl-2 of pulmonary epithelium on endotoxin-induced acute lung injury.Methods 60 rats were randomly divided into two groups:control group,LPS group.After giving LPS 5mg/kg or NS 4 hours,the respiratory rates and partial pressure of arterial oxygen were measured.Then the rats were killed and the ratios of W/D of lung tissue were detected.The Bcl-2-positive cells and Bax-positive cells were measured by using immunocytochemistry.Results After giving LPS,the respiratory rates and the ratios of W/D of lung tissue were higher than those in control group.Partial pressure of arterial oxygen was lower than that in control group.Bcl-2-positive cells had no significant difference between two groups,and Bax-positive cells were higher than those in control group.Conclusion The increasing of Bax-positive cells induced the apoptosis might be the mechanism of ALI.

The Role of the Lactate Dehydrogenase and the Effect of Prone Position during Ventilator-induced Lung Injury

To examine the impact of lactate dehydrogenase (LDH) as an early marker of ventilator-induced lung injury (VILI) and the effect of prone position during the VILI, we ventilated 28 normal white rabbits (10 supine, 10 prone, 8 controls) for 6 hr or until PaO2/FIO2 ratio was<200 mmHg. We applied an identical injurious ventilatory pattern (peak inspiratory pressure of 35 cmH2O with a PEEP of 3 cmH2O, I:E ratio of 1:2, and FIO2 of 0.40) in the supine and prone group. VILI was assessed by oxygenation, gravimetric analysis and histologic grading. Serum levels of LDH progressively increased significantly during the VILI (supine and prone groups) as compared with controls. There was a significant negative correlation between oxygenation and LDH levels (r=-0.619, p<0.001). Wet weight/dry weight ratios (WW/DW) and histologic scores for dependent regions were significantly higher in the supine than the prone group. There were no differences in WW/DW and histologic scores for nondependent regions between the supine and prone group. These findings suggest that serum LDH levels might be an early marker of severity of lung injury. The prone position resulted in a less severe and more homogenous distribution of VILI.

A Practical Protocol for Titrating "Optimal" PEEP in Acute Lung Injury: Recruitment Maneuver and PEEP Decrement

This study was conducted to evaluate the effectiveness and safety of a practical protocol for titrating positive end-expiratory pressure (PEEP) involving recruitment maneuver (RM) and decremental PEEP. Seventeen consecutive patients with acute lung injury who underwent PEEP titration were included in the analysis. After baseline ventilation, RM (continuous positive airway pressure, 35 cm H2O for 45 sec) was performed and PEEP was increased to 20 cmH2O or the highest PEEP guaranteeing the minimal tidal volume of 5 mL/kg. Then PEEP was decreased every 20 min in 2 cmH2O decrements. The "optimal" PEEP was defined as the lowest PEEP attainable without causing a significant drop (>10%) in PaO2. The "optimal PEEP" was 14.5 +/- 3.8 cmH2O. PaO2 /FI O2 ratio was 154.8 +/- 63.3 mmHg at baseline and improved to 290.0 +/- 96.4 mmHg at highest PEEP and 302.7 +/- 94.2 mmHg at "optimal PEEP", both significantly higher than baseline (p<0.05). Static compliance was significantly higher at "optimal" PEEP (27.2 +/- 10.4 mL/ cmH2O) compared to highest PEEP (22.3 +/- 7.7 mL/cmH2O) (p<0.05). Three patients experienced transient hypotension and one patient experienced atrial premature contractions. No patient had gross barotrauma. PEEP titration protocol involving RM and PEEP decrement was effective in improving oxygenation and was generally welltolerated.

Interleukin-4 decreases expression of epithelial sodium channel ?-subunit in A549 cells / 第三军医大学学报

Objective To observe the effects of IL-4 on the expression of epithelial sodium channel(ENaC) ?-subunit.Methods A549 cells were cultured with IL-4 at the concentration of 0,0.1,1 and 10 ng/ml for 12 h or with 1 ng/ml IL-4 for 3,6,12,24 and 48 h.Then ?-ENaC protein and mRNA expressions were detected by Western blotting and RT-PCR respectively.Results IL-4 decreased the expression of ?-ENaC in A549 cells in a time-and dose-dependent manner,via gene transformation.When A549 cells were cultured with IL-4 at the concentration of 1 ng/ml for 3,6,12,24 and 48 h,the expression of ?-ENaC protein and mRNA were decreased in a time-dependent manner.Statistical analysis showed culture for 6 h had a significant difference compared with other time points(P

The Protective and Therapeutic Effects of Anisodamine on Acute Lung Injure and Its Molecular Mechanism / 中国医师杂志

To examine the protective action and therapeutic effect of anisodamine on acute lung injure and its molecular mechanism,63 rats were randomly divided into three groups :normal control group(NS),lipopolysaccharide (LPS) group and anisodamine (ADM) group.Rat model of acute lung injure(ALI) was produced by injecting LPS(5mg/kg) into the tail vein.The lung index(LI),WBC count,the percentage of polymorphonuclear leukocyte(PMN) in the bronchoalveolar lavage fluid(BALF) were observed at 0,1,3,5 hours(T 0,T 1,T 2,T 3).The concentration of TNF-? were measured both in BALF and plasma at four time points.The expression of P65 was analyzed by immunohistochmical method five hours after injecting LPS.The results showed that LI of ADM group were significantly lower than that of LPS group at T 2 after injecting LPS(P

Peroxisome proliferator-activated receptor ? agonist attenuates ICAM-1 and CINC-1 expression in lungs of rats with acute lung injury / 中国病理生理杂志

AIM: To investigate the effects of rosiglitazone(ROSI),an agonist of peroxisome proliferator-activated receptor ?(PPAR?),on the lung expression of intercellular adhesion molecule-1(ICAM-1) and cytokine-induced neutrophil chemoattractant(CINC) in rats with acute lung injury. METHODS: Thirty-six male Wistar rats were randomly divided into six groups: control group,ROSI group,GW9662(a PPAR? antagonist) group,lipopolysaccharide(LPS,6 mg/kg,iv) group,ROSI-LPS group(0.3 mg/kg ROSI iv 30 min prior to LPS) and GW9662-ROSI-LPS group(0.3 mg/kg GW9662,iv,20 min before ROSI).Four hours after LPS injection,wet/dry weight(W/D) ratio,myeloperoxidase (MPO) activity,malondialdehyde(MDA) and CINC-1 concentrations were assayed in the lung tissues.Immunohistochemical analysis of ICAM-1 expression was also studied.RESULTS: Pretreatment with ROSI significantly attenuated LPS-induced increases in W/D ratio,MPO activity,MDA and CINC-1 concentrations as well as ICAM-1 expression in the lung tissues.The specific PPAR? antagonist GW9662 antagonized the effects of ROSI.CONCLUSION: Pretreatment with ROSI reduces LPS-induced lung injury in rats.The mechanism involves inhibition of the lung expression of ICAM-1 and CINC-1 by the activation of PPAR?.

Effects of N~G-nitro-L-arginine on LPS-induced lung injury in rats / 中国病理生理杂志

AIM: To investigate the effects of nitric oxide (NO) and NO synthase (NOS) inhibitor NG-nitro-L arginine (L-NA) on LPS induced-lung injury in rats. METHODS: Forty healthy male SD rats, weighing 300?20 g, were used. The animals were anesthetized with 20% urethane 1 g?kg -1. Common carotid artery (CAA) and jugular vein were exposed through a median incision in the neck. Mean arterial pressure (MAP) was measured through a pressure transducer connected with intubation of CAA. The animals were randomly divided into five groups: group 1: control; group 2: LPS (5 mg?kg -1, iv); group 3: high dose L-NA (20 mg?kg -1 intraperitoneal injection, ip); gropu 4: middle dose L-NA (10 mg?kg -1, ip); group 5: low dose L-NA (5 mg?kg -1, ip). Group1 : 0.9% saline solution was given and the animals were killed 6 h after the saline solution. Gruop 2: saline solution was given 3 h after LPS and the animals were killed 3 h after administration. Group 3, 4 and 5: L-NA was given 3 h after LPS iv and the animals were killed 3 h after administration, respectively. The pulmonary was removed immediately. The pulmonary coefficient and water content in pulmonary tissue were calculated (%). The NO 2-/NO 3- content in plasma, MDA content and NOS, SOD activity in the pulmonary tissue were measured. RESULTS: L-NA significantly decreased pulmonary coefficient and water content in pulmonary tissue and ameliorated LPS induced lung injury. The effect in high dose group was better than that in low dose group. L-NA significantly decreased NO 2-/NO 3- content in plasm, decreased MDA content and inhibited NOS activity and enhanced SOD activity in the pulmonary tissue. CONCLUSION: It may be concluded that L-NA has a beneficial effect on lung injury induced by LPS.

Antagonistic effect of bilirulin on acute lung injury induced by LPS in rats / 中国病理生理杂志

AIM: To investigate the effect of bilirub in on acute lung injury (ALI) and the mechanism. METHODS: 30 male Wistar rats were divided into normal group, ALI group and bilirubin treatment group. Lung specimens were examined by histopatho logical te chnique. Lung index (LI) and lung permeability index (LPI) were measured. Moreov er, white blood cell (WBC) count, neutrophil percentage (PMN%) and the content o f protein (Pr) in the bronchoalveolar lavage fluid (BALF), as well as the conten ts of sup eroxide dismutase (SOD), malonaldehyde (MDA) and glutathione peroxidase (GSH-Px) in the lung homogenate were determined. RESULTS: (1) In ALI group: LI, WBC count, PMN%, Pr and LPI incre ased significantly compared with normal group (P 0.05) was observed. (2) In ALI group, the content of MDA was significantly high er (P0.05). CONCLUSION: Bilirubin relieves ALI induced by LPS in rats via an tioxidation.