Curcumin upregulates mitofusin 2 to alleviate acute lung injury in septic mice / 中华急诊医学杂志

Objective To investigate the protective effect and mechanism of curcumin on acute lung injury in septic mice.Methods Totally 120 clean BALB/c male mice were randomly (random number) divided into 8 groups:sham group,sepsis group,curcumin control group,curcumin intervention group,negative virus-sepsis group,negative virus-curcumin intervention group,Mfn2 interference-sepsis group,and Mfn2 interference-curcumin intervention group,15 rats in each group.Mice in the sepsis and the curcumin groups were given the cecal ligation and puncture (CLP) mice in the curcumin intervention and curcumin control groups were given curcumin 200 mg/(kg·d) for 1 week,and mice in the negative virus-sepsis group and negative virus-curcumin intervention groups were established by injection of a negative adeno-associated virus in the tail vein.The Mfn2 interference-sepsis and Mfn2 interference-curcumin intervention groups were established by injecting an adeno-associated virus carrying the Mfn2 interference sequence through the tail vein.Mice were sacrificed after 24 h in each group.The degree of lung injury was examined by lung wet-to-dry weight ratio and pathological examination.The inflammatory factors of alveolar lavage fluid including TNF-α and IL-6 were detected by ELISA,the activation of caspase-3,a key molecule for apoptosis,was detected by Western blot,and apoptosis was detected by TUNEL.The data were analyzed by SPSS 22.0 software,the count data was analyzed by x2 test,and the comparison of measurement data between groups was analyzed by one-way ANOVA.Results Compared with the sham group,the wet-to-dry weight ratio of lung tissue in the sepsis group was significantly increased (71.11 ± 3.78 vs 31.11 ± 5.61,P=0.002),the histopathological score was significantly higher (P=0.006),the inflammatory factors TNF-α (P=0.001) and IL-6 (P=0.012) were dramatically increased,and the apoptosis of lung tissue and the expression of caspase-3 cleaved were also significantly increased (P=0.001).Compared with the sepsis group,the wet-to-dry weight ratio and the histopathological score of lung tissue in the curcumin-treated group was significantly lower (32.84 ± 6.15 vs 71.11 ± 3.78,P=0.004),and the inflammatory factors TNF-α(P=0.013) and IL-6 (P=0.003) were obviously decreased,and apoptosis and apoptosis-related protein caspase-3 cleaved expression were also dramatically decreased (P=0.012).After Mfn2 was down-regulated,Mfn2 interference-curcumin intervention group interfered with Mfn2.Compared with the sepsis group,the dry-to-wet weight ratio and the histopathological score of the lung tissue of the mice was not significantly decreased.Further studies found that after down-regulating Mfn2,compared with the Mfn2 interfere-sepsis group,Mfn2 interfere-curcumin intervention group had no such performance.The inflammatory factors TNF-α and IL-6 were not significantly decreased,and the apoptosis of lung tissue and the expression of apoptosis-related protein caspase-3 cleaved were not significantly reduced.Conclusion Curcumin may attenuate acute lung injury in sepsis by up-regulating the expression of Mfn2.

Antioxidant mechanism of HDAC2 regulating Nrf2 acetylation in LPS-induced type Ⅱ alveolar epithelial cell injury / 中华急诊医学杂志

Objective To explore the antioxidant mechanism ofhistone deacetylase 2 (HDAC2) regulating Nrf 2 acetylation in lipopolysaccharide (LPS)-induced type Ⅱ alveolar epithelial cell injury.Methods The experiment was divided into two parts.The first part was the routine culture of type Ⅱ alveolar epithelial cells of mice.The cells were stimulated with different concentrations of LPS (10 ng/ mL,100 ng/mL and 1 000 ng/mL).CCK-8 was used to detect the cell activity at 0 h,6 h,12 h,24 h and 48 h,respectively.The second part:Alveolar epithelial cells of type Ⅱ were cultured and divided into the normal control group (control group),LPS group,HDAC2 lentivirus interference group (siRNA-HDAC2 group) and HDAC2 lentivirus overexpression group (LV-HDAC2 group).The expression of HDAC2 and Nrf2 were detected by Western blot,the acetylation of Nrf2 was detected by immunoprecipitation,and the stability of nrf2 was detected after actinidone action.The activity of superoxide dismutase (SOD) and malondialdehyde (MDA) were detected by chemical colorimetry.SPSS 23.0 statistical software was used.LSD-t test was used for comparison between two groups,and one-way ANOVA test was used for comparison among multiple groups.Results Compared with the control group,the expression of HDAC2 protein in the LPS group increased (t=5.974,P=0.027),the acetylation level of Nrf2 decreased (t=7.223,P=0.002),the Nrf2 protein level increased (t=2.929,P=0.043),the protein stability of Nrf2 increased,the SOD activity decreased (t=121,P＜0.01),and the MDA content increased (t=10.45,P=0.000 5).Compared with the LPS group,Nrf2 acetylation level decreased in the LV-HDAC2 group (t=1 1.29,P=0.000 4),Nrf2 protein expression increased (t=3.194,P=0.033),Nrf2 protein stability increased,SOD activity increased (t=4.678,P=0.009),and MDA content decreased in the LV-HDAC2 group (t=5.417,P=0.005 6).While the opposite trend was observed in the siRNA-HDAC2 group.Conclusion After LPS stimulation,oxidative stress of type Ⅱ alveolar epithelial cells was aggravated.HDAC2 could decrease the level of Nrf2 acetylation,increase the expression of Nrf2 protein,and alleviate LPS-induced oxidative stress.

Protective effect of Baicalin on lipopolysaccharide induced H9C2 cell inflammation and its mechanism / 中华急诊医学杂志

Objective To investigate the protective effect of Baicalin on inflammation induced by lipopolysaccharide in H9C2 cardiomyocytes and its possible mechanism. Methods H9C2 myocardial cells were cultured and pretreated with baicalin at the final concentration of 10, 20, 30 μmol/L for 12 hours, then stimulated with LPS at the final concentration of 1 μg/mL for 6 hours. The control group was treated with the same amount of saline to collect cell samples. CCK-8 (The Cell Counting Kit-8) was used to detect cell activity, enzyme-linked immunosorbent assay (ELISA) was used to detect the expression levels of interleukin-6 (IL-6), interleukin-1beta (IL-1β), tumor necrosis factor-alpha (TNF-α), Western blot was used to detect the protein expression levels of NF-κB p65, p-NF-κB p65, p38 MAPK, p-p38 MAPK, IκBα and p-IκBα. SPSS 23.0 statistical software was used. Independent sample t test was used for comparison between two groups, and one-way ANOVA test was used for comparison among multiple groups. Results The survival rate of myocardial cells in the control group was (93.67 +1.453)％. Compared with the control group, the survival rate of H9C2 myocardial cells induced by LPS decreased (P< 0.05). In the control group, the expression of IL-6 in H9C2 myocardial cells was (49.33 +2.42) pg/mL, the expression of TNF-α was (86.33 +1.85) pg/mL, and the expression of IL-1β was (28.67 +4.66) pg/mL. Compared with the control group, the expression levels of IL-6, IL-1β and TNF-α in H9C2 myocardial cells increased after LPS induction (P< 0.05), while the levels of p-NF-κ B p65, p-p38 MAPK and p-I κ B α protein increased (P< 0.05), while the levels of I κ B α protein decreased (P< 0.05), while the expressions of NF-κ B p65 and p38 MAPK protein did not change significantly (P> 0.05). Compared with LPS group, the survival rate of H9C2 myocardial cells in baicalin intervention group increased (P<0.05), the expression levels of IL-6, IL-1β and TNF-a decreased (P < 0.05), the levels of p-NF-κB p65, p-p38 MAPK, p-I κBα protein decreased (P< 0.05), and the level of IκBα protein increased (P< 0.05), while the expression of NF-κB p65 and p38 MAPK did not change significantly. (P>0.05). Conclusions Baicalin may alleviate LPS-induced cardiomyocyte inflammation by inhibiting the activation of NF-kappa B and p38 MAPK, and improve cell survival.

Clinical analysis of 22 cases of syndrome caused by acute poisoning / 中华劳动卫生职业病杂志

Objective@#To analyze the clinical characteristics, treatment and prognosis of rhabdomyolysis (RM) caused by acute poisoning.Summarize the clinical characteristics and treatment experience, pay attention to the complications and improve the quality of rescue.@*Methods@#We collecte and summarize the clinical data, treatment and prognosis of 22 cases of RM caused by acute poisoning.@*Results@#We found that 21 patients (95.5%) had muscle damage, 13(59.1%) with coma, 8(36.4%) with brown, tea or even soy sauce urine, 6(27.3%) had acute renal injury (AKI), and 4(18.2%) had multiple organ dysfunction syndrome (MODS). After the treatment, 21 cases (95.5%) got better, and one case were discharged. All the patients with AKI were survived, three of them were treated by hemodialysis, and the other recovered gradually after massive fluid replacement.@*Conclusion@#Acute poisoning combined with RM is not uncommon in clinic. We should pay attention to examination of serum enzymes and other indicators, observe the clinical symptoms and make early diagnosis. The key to diagnosis and treatment is early fluid resuscitation, comprehensive treatment, blood purification and maintain the stability of water and electrolyte.

Protective effects of histone deacetylase inhibitors trichostatin A on acute lung injury in septic mice / 中华急诊医学杂志

Objective To investigate the effects of histone deacetylase inhibitors trichostatin A (TSA) on acute lung injury in septic mice.Methods Septic mice model was induced by cecal ligation and puncture(CLP).Ninty male BALB/c mice of clean grade were randomly(random number) divided into six groups(n=15),namely sham operation group,CLP group,CLP+DMSO group,CLP+TSA 1 mg group,CLP+TSA 5 mg group,and CLP+TSA 10 mg group.TSA(1 mg/kg,5 mg/kg,10 mg/kg) was administrated 12 hours before operation by intraperitoneal injection.And mice in sham group were only treated with laparotomy without CLP,and 24 h later,all survived mice were sacrificed to obtain specimens.ELISA method was employed to detect the concentrations of TNF-α and IL-1β in BALF.The lung wet/dry ratio was calculated.Histopathology changes of lung tissues were observed under light microscope.Lung tissue cell apoptosis was detected by TUNEL method.Caspase-3,Caspase-9 and CytC were assayed by Western blotting.The survival rate of mice in each group was calculated by additional 120 mice.Data were analyzed by SPSS 23.0.Statistical analyses were performed using independent sample t-test to compare between two groups or one-way analysis of variance test to compare among muhiple groups.The survival rate of mice was analyzed by univariate analysis using log-rank test.Results The lung W/D(P=0.021),the concentrations of TNF-α(P=0.000 1)and IL-1β(P=0.000 6)in BALF,puhnonary pathological change(P=0.001 6),lung tissue cell apoptotic index(P=0.000 9),the levels of apoptosis proteins (P＜0.05) in CLP group were higher than those in sham group,while survival rate (P=0.000 1) in CLP groups was lower than that in sham group.Compared with DMSO,the TSA significantly reduced the lung W/D,the levels of TNF-α.IL-1β in BALF,pathologic changes of lung tissue,lung tissue cell apoptotic index and the levels of apoptosis proteins in septic mice(P＜0.05).The increase in survival rate (P=0.007 2) associated with TSA(10 mg/kg)administration.Conclusion TSA exerts protective effects through attenuating pro-inflammatory cytokines and lung tissue cell apoptosis in sepsis induced acute lung injury in mice.

The effects of miR-10a on the immune function of splenic CD4+CD25+ Treg cells in septic mice / 中华急诊医学杂志

Objective To investigate the role of miR-10a in CD4+CD25+Treg-mediated immunosuppression during sepsis and its potential role in immunotherapy for sepsis.Methods Sepsis mouse model was established by cecal ligation and puncture(CLP).Balb/c mice of clean grade were sacrificed 1,3,5,and 7 days after operation.Blood as well as spleen samples were harvested at given intervals.The splenic CD4+CD25+Treg cells and CD4+T cells were isolated by MACS microbeads.Cells were cultured,and phenotypes were analyzed by flow cytometry.The miR-10a expressed in Treg cells were detected by Real-time PCR.After administration of LV-mmu-miR-10a-5p-inhibition,the immunosuppressive function have been detected.Statistical analyses were performed using one-way analysis of variance (SPSS 19.0,Chicago,USA) test followed by Dunnett-t test to compare among three or more groups or by Student's t-test to compare between two groups.Results The percentages of splenic Tregs (CD4+CD25+/CD4+T) was (7.34±1.2)％ in normal group,and the increase in percentage of Tregs in spleen has been observed in septic mice (P＜0.05).The mean fluorescence intensity (MFI) of Foxp3+Treg was increased in septic mice compared with sham group (P＜0.05).The expression of miR-10a was significantly elevated on CLP 1-7 day (P＜0.05).After down-regulation of miR-10a in septic mice,the percentages of Tregs (CD4+CD25+/CD4+T) was significantly increased in septic mice (P＜0.05),the MFI of Foxp3+Treg was increased in septic mice compared with control group (P＜0.05).The CD4+T cell proliferative activity in CLP-induced mice was significantly suppressed on CLP 3 day compared with sham group (P＜0.05).After down-regulation of miR-10a in septic mice,the CD4+T cell proliferative activity was significantly suppressed compared with control group (P＜0.05).Conclusions Treg plays a critical role in immunosuppression in septic mice.Inhibition of miR-10a in vivo could enhence immunesuppression of CD4+CD25+Treg.Therefore miR-10a may participate in the regulation of CD4+CD25+Treg immunosuppression in sepsis and become the target for immunotherapy.

Analyses on relevant factors of the prognosis of elderly patients with acute poisoning / 中华劳动卫生职业病杂志

Objective@#To explore the risk factors influencing the prognosis of elderly patients with acute poisoning.@*Methods@#We retrospected 177 elderly patients with Acute Poisoning who were treated in the emergency department of the first affiliated hospital of wenzhou medical university from July 2009 to May 2015. According to the outcome of patients, we distributed the patients to death group (31 cases) and survival group (146 cases) , compared the clinic data and using multivariate analysis with Logistic regression to prognosis factors.@*Results@#There were 177 cases in total, with 146 survivors (82.5%) and 31 deaths (17.5%) . In which 102 cases (57.6%) had chronic underlying diseases. There were 28 cases of pesticide poisoning in the death group, and the fatality rate of pesticide poisoning was 23.5%. The mortality rate was 12.8% in the 60-69 years-old group (11/86) , 20% (13/65) in the 70-79 years-old group, 26.9% (7/26) in the 80-89 years-old group. The most common reason of poisoning was intentional ingestion, with 100 cases (56.5%) . The tract of the poisoning was mainly in digestive system, including 148 cases (83.6%) . The PSS score and APACHE-II score were 2.97±0.18 and 19.8±2.8 in the death group, 2.27±0.81 and 12.8±5.3 in the survival group. Compared with the survival group, poison (pesticides or non) 、poisoning route、cause of poisoning、PSS score、APACHEⅡ score have significant difference in death group (P<0.05) . Poison (pesticides or non) 、PSS score、APACHEⅡ, were the independent risk factors of poor prognosis.@*Conclusion@#Most of the elderly patients with acute poisoning have one or more chronic underlying diseases, the digestive tract ingestion and pesticide poisoning are more common. The fatality rate of the old patients is significantly higher than that of non elderly poisoning. Type of toxications, PSS score and APACHE-II score are the prognostic factors in elderly patients.

The effect of resveratrol on paraquat-induced acute lung injury in mice and its mechanism / 中华危重病急救医学

Objective To investigate the effect of resveratrol (Res) on paraquat (PQ)-induced acute lung injury (ALI) and mortality in mice and the mechanism of nuclear factor-κB (NF-κB) inflammatory pathway. Methods Sixty-eight healthy male ICR mice with grade SPF were enrolled, among them 20 mice were used for mortality observation (n = 10), and other 48 were used for determination of related parameters (n = 6). The mice were randomly divided into four group s: normal saline (NS) control group, Res control group, PQ group and PQ + Res group. The mice in the latter two groups were subdivided into 6, 24, 72 hours subgroups. The PQ poisoning model of mice was reproduced by one injection of 30 mg/kg PQ intraperitoneally. The mice in PQ + Res group were given 60 mg/kg Res intraperitoneally on the contralateral side after PQ injection. The mice were sacrificed at 6, 24, 72 hours after PQ poisoning, and lung tissue was harvested. The serum levels of tumor necrosis factor-α (TNF-α), interleukins (IL-6 and IL-1β) were determined by enzyme linked immunosorbent assay (ELISA). The pathological changes in lung tissue were observed with electron microscopy. Apoptosis cells in the lung were identified by terminal dexynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) for the estimation of apoptosis rate. The protein expression of NF-κB p65 was determined by Western Blot. Results Compared with PQ group, the death number of mice at 48, 72, 96 hours in PQ + Res group was slightly decreased (0 vs. 2, 2 vs. 5, 4 vs. 6) but without statistically significant difference (all P > 0.05). Under electron microscope, the lung injury in PQ group was severer than that in NS control group, and Res was found to be able to alleviate the lung injury. Compared with NS control group [(2.45±0.61)%], the apoptosis rate at 6 hours in PQ group was significantly increased [(8.42±1.48)%], and peaked at 72 hours [(21.23±3.47)%]. Res could decrease the apoptosis rate after PQ poisoning [6 hours: (5.56±1.31)% vs. (8.42±1.48)%, 24 hours: (11.14±2.07)% vs. (16.88±2.96)%, 72 hours: (13.28±2.32)% vs. (21.23±3.47)%, all P < 0.05]. The serum levels of TNF-α, IL-6, and IL-1β, and NF-κB p65 in lung tissue were all markedly increased after PQ poisoning, and they were significantly decreased after Res intervention as compared with those of PQ group [TNF-α (ng/L): 2.62±0.29 vs. 4.06±0.74 at 6 hours, 3.98±0.41 vs. 6.79±0.80 at 24 hours, 5.06±0.75 vs. 11.00±0.75 at 72 hours; IL-6 (ng/L): 14.19±1.54 vs. 16.55±1.24 at 6 hours, 13.21±1.37 vs. 19.73±0.85 at 24 hours, 13.72±0.56 vs. 22.45±0.72 at 72 hours; IL-1β (ng/L): 8.54±1.64 vs. 12.59±0.66 at 6 hours, 10.15±0.29 vs. 16.24±1.03 at 24 hours, 16.14±0.70 vs. 19.55±0.56 at 72 hours; 6-hour NF-κB p65: (1.34±0.07) folds vs. (1.86±0.11) folds when the expression in NS control group was represented as 1, all P < 0.05]. Conclusions Res cannot lower the mortality in mice with PQ poisoning, but it seems to be able to attenuate PQ-induced ALI and cell apoptosis. The mechanism responsible for the latter maybe the inhibitive effect of Res on NF-κB p65 translocation and cytokines production.

The protective effect of bone marrow mesenchymal stem cells carrying antioxidant gene superoxide dismutase on paraquat lung injury in mice / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To explore the possible mechanism and protective effect of BMSCs (bone mesenchymal stem cells) carrying superoxide dismutase (SOD) gene on mice with paraquat-induced acute lung injury.</p><p><b>METHODS</b>To establish the cell line of BMSCs bringing SOD gene, lentiviral vector bringing SOD gene was built and co-cultured with BMSCs. A total of 100 BALB/c mice were randomly divided into five groups, namely Control group, poisoning group (PQ group) , BMSCs therapy group (BMSC group) , BMSCs-Cherry therapy group (BMSC-Cherry group) , BMSCs-SOD therapy group (BMSC-SOD group) . PQ poisoning model was produced by stomach lavaged once with 1 ml of 25 mg/kg PQ solution, and the equal volume of normal saline (NS) was given to Control group mice instead of PQ. The corresponding BMSCs therapy cell lines were delivered to mice through the tail vein of mice 4h after PQ treatment.Five mice of each group were sacrificed 3 d, 7 d, 14 d and 21 days after corresponding BMSCs therapy cell lines administration, and lung tissues of mice were taken to make sections for histological analysis. The serum levels of glutathione (GSH) , malondialdehyde (MDA) , SOD, and the levels of transforming growth factor-β (TGF-β) and tumor necrosis factor-α (TNF-α) in lung tissue were determined. The level of SOD was assayed by Westen-blot.</p><p><b>RESULTS</b>Compared with Control group, the early (3 days) levels of SOD protein in lung tissue of PQ group obviously decreased, and the late (21 days) levels of SOD obviously increased, while in therapy groups, that was higher than that in PQ group, and the BMSCs-SOD group showed most obvious (all P<0.05) . Compared with Control group, the levels of plasma GSH and SOD of PQ group and each therapy group wae significantly lower than those in Control group, while in therapy groups, those were higher than those of PQ group, and the BMSCs-SOD group showed most obvious (all P<0.05) .Compared with Control group, the level of plasma MDA, TNF-α and TGF-β in PQ group and therapy groups were significantly higher, while in therapy groups, that was lower than that in PQ group, and the BMSCs-SOD group showed most obvious (all P<0.05) . Lung biopsy showed that, the degree of lung tissue damage in each therapy group obviously reduced.</p><p><b>CONCLUSION</b>SOD is the key factor of the removal of reactive oxygen species (ROS) in cells, that can obviously inhibit the oxidative stress damage and the apoptosis induced by PQ, thus significantly increasing alveolar epithelial cell ability to fight outside harmful environment.</p>

The clinicalvalue of procalcitoninin the condition and prognosis of patients with sepsis / 中华急诊医学杂志

Objective To explore the clinical value of procalcitonin (PCT)in the disease severity and prognosis of patients with sepsis,and the relationship between PCT and acute physiology and chronic health evaluation Ⅱscore (APACHEⅡscore).Methods Clinical data (including the value of PCT,the count of the white blood cell WBC and the percent of neutrophils percentage Neut%,APACHEⅡ score,et al,within 24 hours after admission)of 109 sepsis patients admitted to the emergency department (including the general ward and emergency intensive care unit EICU)and infections department of our hospital from January 1st 2013 to December 31st 2014 were retrospectively analyzed.The patients were divided into several groups according to the patients condition (the sepsis group,the severe sepsis group and the septic shock group),the clinical outcomes (the survival group and the dead group ),and multiple organ dysfunction syndrome MODS (the MODS group and the non-MODS group),comparing the differences of all markers in each group;to analyze the correlation between PCT and APACHEⅡ score;to assess the value of PCT,APACHE Ⅱ score and APACHE Ⅱ score +PCT for prognosis and multiple organ dysfunction syndrome of patients with sepsis;to have a understanding of the independent effect of PCT on the prognosis andthe factors of prognosis in patients with sepsis.Results The value of PCT,APACHEⅡ score in sepsis group was lower than the severe sepsis group and the septic shock group,also the severe sepsis was lower than the septic shock group,and each group was significantly different (P <0.05).Compared with the septic shock group,the count of WBC of sepsis group was significantly lower (P <0.05).Also the dead group compared with the survival group,the APACHEⅡ score was significantly increased (P <0.01),but the values of PCT,WBC,Neut% were not significantly different.The values of APACHEⅡ score,WBC, Neut%,PCT in the non-MDOS group were significantly lower than those in the MODS group (all P <0.05).The relationship between the values of PCT and APACHEⅡ score was significantly correlated (rs=0.403,P <0.01 ).Using the receiver operating characteristic curve (ROC ) for evaluating the prognosis,the area under curve (AUC)of PCT,APACHE Ⅱ score and the PCT +APACHE Ⅱ score respectively were 0.617,0.899,0.917,and the last two were significantly better (all P <0.01),also the cut-off,sensitivity and specificity of PCT,APACHE Ⅱ score were respectively (3.40 ng/mL, 88.24%,38.04%),(20 scores,94.12%,81.52%).As the same to evaluating MODS,the AUC of PCT,APACHEⅡ score and APACHE Ⅱ score +PCT respectively were 0.824,0.796,0.871,the assessed value between PCT and APACHEⅡ score,between PCT and APACHEⅡ score +PCT were not significantly different;also the cut-off,sensitivity and specificity of PCT,APACHEⅡ score respectively were (7.26 ng/mL,88.24%,63.79%), (17 scores,64.71%,87.93%).The COR and AOR of PCT for the prognosis were respectively 1.008,1.014,and gender and APACHE Ⅱ score were the two independent risk factors for the prognosis in patients with sepsis.Conclusions The value of PCT and APACHEⅡ score could evaluate the severity of illness in sepsis patients,and the three were positive correlations.APACHEⅡ score,APACHEⅡ score +PCT had a significantly higher prognostic value than PCT,and PCT could not be a independent marker.But for assessing the MODS in patients with sepsis,the assessed value of PCT,APACHEⅡ score,APACHEⅡ score +PCT were medium.Gender and APACHEⅡ score were the two independent risk factors for the prognosis in patients with sepsis.

The protective effect of regulation of paraoxonase 1 gene on liver oxidative stress injury induced by dichlorvos poisoning in mice / 中华危重病急救医学

ObjectiveTo investigate the protective effect of paraoxonase 1 (PON1) gene against liver oxidative stress injury in mice due to dichlorvos poisoning.Methods Experiment 1: 12 male Balb/c mice were randomly divided into three groups, with 4 mice in each group: control group, green fluorescent protein lentivirus control group (Lv-GFP group), and recombinant PON1 lentivirus group (Lv-PON1 group). 2×107 TU of Lv-GFP or Lv-PON1 was transfected via tail vein, while normal saline was given to those in control group. Blood was collected on 0, 1, 3, 5, 7, 9 days via fundus venous plexus for the assay of serum PON1 activity. PON1 mRNA and protein expression levels were respectively determined by reverse transcription-polymerase chain reaction (RT-PCR) and Western Blot on the 3rd post-lentivirus transfection day. Experiment 2: according to the random number table method, another 96 male Balb/c mice were divided into four groups of 24 mice in each control group, dichlorvos group, Lv-GFP intervention group, and Lv-PON1 intervention group. Lv-GFP or Lv-PON1 was transfected via tail vein followed by intraperitoneal injection of dichlorvos 9 mg/kg, while those in control group were given normal saline. Six mice in each group were sacrificed respectively at 6, 12, 24, 48 hours, and liver tissue was collected. PON1 mRNA and nuclear factor E2-related factor 2 (Nrf2) mRNA expression levels were determined by RT-PCR, and PON1 protein level was determined by Western Blot. The content of malondialdehyde (MDA) and glutathione (GSH) in the liver tissue were determined by chemical colorimetry. The activity of superoxide dismutase (SOD) and catalase (CAT) were measured by double antibody sandwich enzyme linked immunosorbent assay (ELISA).Results Experiment 1: after Lv-PON1 was transfected to normal mice, PON1 activity in serum gradually increased and maintained a high level on 3rd day, while that of the control group and Lv-GFP group showed a normal low level. On the 3rd post-lentivirus transfection day, PON1 mRNA and PON1 protein expressions in liver were significantly higher than those of control group and Lv-GFP group. Experiment 2: compared with control group, the mice in dichlorvos group showed significant decreases in PON1 mRNA, PON1 protein, Nrf2 mRNA as well as GSH, SOD, CAT levels at 6 hours [PON1 mRNA (gray value):0.237±0.075 vs. 0.674±0.011, PON1 protein (gray value): 0.602±0.086 vs. 0.998±0.124, Nrf2 mRNA (gray value): 0.089±0.012 vs. 0.126±0.010, GSH (mg/g): 3.84±0.33 vs. 5.52±0.40, SOD (μg/g): 0.383±0.040 vs. 0.564±0.052, CAT (ng/g): 7.32±1.28 vs. 12.46±1.54, allP 0.05), and it was higher than that of the control group at 48 hours (0.206±0.028 vs. 0.124±0.010,P< 0.05). Compared with that of the dichlorvos group, Lv-PON1 intervention group showed a significant increase in PON1 mRNA, PON1 protein, Nrf2 mRNA and GSH, SOD, CAT levels [PON1 mRNA (gray value): 0.726±0.021 vs. 0.237±0.075, PON1 protein (gray value): 0.739±0.050 vs. 0.602±0.086, Nrf2 mRNA (gray value): 0.158±0.007 vs. 0.089±0.012, GSH (mg/g): 4.30±0.22 vs. 3.84±0.33, SOD (μg/g): 0.454±0.062 vs. 0.383±0.040, CAT (ng/g): 8.98±1.02 vs. 7.32±1.28, allP< 0.05], and a decrease in MDA content (nmol/g: 6.56±0.44 vs. 7.78±0.41,P< 0.05).Conclusion Regulation of PON1 gene can reduce MDA content, enhance SOD and CAT activities, increase GSH content, and it may also up-regulate Nrf2 mRNA expression to play a protective effect against oxidative stress of liver injury induced by dichlorvos poisoning.

The protective effect of bone marrow mesenchymal stem cell on lung injury induced by vibrio vulnificus sepsis / 中华危重病急救医学

Objective To discuss the protective effect of bone marrow mesenchymal stem cell(BMSC)on lung injury induced by vibrio vulnificus sepsis and its mechanism. Methods BMSCs were isolated by whole bone marrow adherent culture from mouse. Male ICR mice were randomly divided into normal saline control group(NS group),normal saline+BMSC control group(NSB group),vibrio vulnificus sepsis group(VV group),vibrio vulnificus sepsis + BMSC group(VVB group)according to random number table,with 40 mice in each group. Sepsis mouse model was reproduced by injecting vibrio vulnificus(1×107 cfu/mL)5 mL/kg through the left side peritoneal cavity, and caudal intravenous injection of BMSC(4×105 cfu/mL)5 mL/kg for intervention after model reproduction. Ten mice in each group were sacrificed at 6,12,24 or 48 hours after injecting vibiro vulnificus,and their lung tissues were harvested. The lung wet/dry(W/D)ratio was calculated. The expression of nuclear factor-κBp65(NF-κBp65)in nucleus was measured by Western Blot. The levels of tumor necrosis factor-α(TNF-α)and interleukins(IL-1β, IL-6)in lung tissue were detected by enzyme-linked immunosorbent assay(ELISA). The pathological changes in lung tissue were observed after hematoxylin-eosin(HE)staining and uranyl acetate-lead citrate staining. Results After vibrio vulnificus injection,lung W/D ratio,the expression of NF-κBp65 in nucleus,and the levels of TNF-α, IL-1β,IL-6 in the lung tissues were significantly increased in VV group compared with those in NS group at all the time points,and peaked at 12 hours. Compared with the VV group,the VVB group had significantly decreased levels of lung W/D ratio,NF-κBp65 expression,and the levels of TNF-α,IL-1β,IL-6,with significant differences at all the time points〔VV group vs. NS group at 12 hours:lung W/D ratio 7.22±0.03 vs. 5.21±0.02,NF-κBp65 expression (glay scale)1.86±0.74 vs. 0.75±0.07,TNF-α(ng/L)433.24±3.23 vs. 106.57±1.21,IL-1β(ng/L)35.64±0.15 vs. 10.64±0.48,IL-6(ng/L)58.84±0.55 vs. 17.69±1.35,all P<0.05;VVB group vs. VV group at 12 hours:lung W/D ratio 6.49±0.06 vs. 7.22±0.03,NF-κBp65 expression(A value)1.16±0.08 vs. 1.86±0.74,TNF-α(ng/L)357.22±3.25 vs. 433.24±3.23,IL-1β(ng/L)27.77±0.59 vs. 35.64±0.15,IL-6(ng/L)38.68±1.29 vs. 58.84±0.55,all P<0.05〕. There were no significant differences in above indexes between NS group and NSB group. In the NS and NSB groups pathological changes were not obvious under light microscopy,in the VV group lung tissue hyperemia and edema was significant,the edema fluid,red blood cells and inflammatory cells also could be seen, and in the VVB group lung damage that mentioned above could be alleviated. In the NS and NSB groups epithelial cell structure of type Ⅰ and type Ⅱ was completed,and the changes were not obvious under the transmission electron microscopy. In the VV group the alveolar walls were damaged significantly,with type Ⅰ epithelial cell cytoplasm swelling,bubbling and rupture,with type Ⅱ epithelial cells visible cytoplasm decrease,cavitation,addiction to osmium lamellar corpuscle emptying,lysosome hyperplasia,microvilli reduction,and in the VVB group the above damage was alleviated. Conclusion Vibrio vulnificus sepsis can cause acute lung damage and edema,and BMSC can down regulate inflammatory cytokines,reduce lung injury caused by vibrio vulnificus sepsis.

Curcumin alleviated liver oxidative stress injury of rat induced by paraquat / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate the effect of curcumin on liver injury in rats induced by paraquat-mediated oxidative stress and the mechanism underlying its effect.</p><p><b>METHODS</b>Sixty rats were randomly divided into 4 groups: control group, curcumin control group (curcumin 50 mg/kg), paraquat group (2% paraquat solution 100 mg/kg), and curcumin intervention group (curcumin 50 mg/kg at 15 min, 24 h, or 48 h after paraquat exposure). On days 1, 3, or 7 after paraquat administration, and liver tissue was collected thereafter. The content of malonaldehyde (MDA) and the activities of superoxide dismutase activity (SOD) and catalase (CAT) in the liver tissue were determined by chemical colorimetry. The activities of heme oxygenase 1 (HO-1) and quinone oxidoreductase 1 (NQO-1) in the liver tissue were determined by ELISA. The mRNA and protein levels of NF-E2-related factor 2 (Nrf2) were determined by RT-PCR and Western blot, respectively. The pathological changes of liver tissue were examined by optical microscopy.</p><p><b>RESULTS</b>No significant change was observed between the control group and the curcumin control group in any examination of this study (P > 0.05). Both paraquat group and curcumin intervention group showed increase in MDA content, decreases in SOD and CAT activities, increases in HO-1 and NQO-1 activities, and increases in the protein and mRNA levels of Nrf2, in comparison with the control group (P < 0.05 for all except HO-1 activity in paraquat group on day 7). In comparison with the parquet group on the same day, the curcumin intervention group showed decrease in MDA content, increases in the activities of SOD, CAT, HO-1, and NQO-1, and increases in the mRNA and protein levels of Nrf2 on days 1, 3, and 7 (P < 0.05). The pathological examination revealed that the damage of liver tissue in the paraquat group was the most serious on the 3rd day after paraquat exposure, and the damage was consistently alleviated by curcumin intervention on days 1, 3, and 7, as compared with the paraquat group.</p><p><b>CONCLUSION</b>Oxidative stress plays an important role in paraquat-induced acute liver damage in rats, and curcumin can exert a hepatoprotective effect against oxidative stress by increasing the expression of Nrf2 and the activities of HO-1, NQO-1, SOD, and CAT and reducing the content of MDA.</p>

Protective effect of ghrelin against paraquat-induced acute lung injury in mice / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To measure the levels of ghrelin-induced expression or activation of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and</p><p><b>NAD(P)H</b>quinone oxidoreductase 1 (NQO1) in the PQ-injured lungs of mice and to evaluate the protective effect of ghrelin against paraquat (PQ)-induced acute lung injury in mice.</p><p><b>METHODS</b>According to the random number table method, 50 ICR mice of clean grade were assigned to 5 groups: normal control group (n = 10), PQ group (n = 10), and ghrelin intervention groups (n = 30). For PQ group, mice were injected with a single dose of PQ (20 mg/kg, i.p.); for ghrelin intervention groups, mice were injected with a single dose of PQ (20 mg/kg, i.p.), and then ghrelin was injected at three concentrations (16.58, 33.15, and 49.73 µg/kg). Lung tissues were collected and proceeded to the following studies. HE staining was used for histopathological examination under a light microscope, and the changes in nuclear expression of Nrf2 were evaluated by Western blot. The activities of HO-1 and NQO1 were measured by ELISA. Malondialdehyde (MDA) content and MPO activity were measured by colorimetry. Another 40 mice were divided into PQ group (n = 10) and 16.58, 33.15, and 49.73 µg/kg ghrelin intervention groups (n = 10 for each); mortality and clinical manifestations were recorded within 72 h.</p><p><b>RESULTS</b>Compared with the normal control group, the PQ group showed significant increases in nuclear protein level of Nrf2, content of MDA, and activities of HO-1, NQO1, and MPO (P < 0.05 for all). Compared with the PQ group, ghrelin treatment significantly increased the expression of Nrf2 and activities of HO-1 and NQO1 and significantly reduced the content of MDA and activity of MPO (P < 0.01 for all). Histopathological studies indicated that ghrelin showed an antioxidant property that reduced the histological changes induced by PQ in the lungs. The ghrelin intervention groups had a significantly lower mortality than the PQ group, and there was a significant difference between the high-dose ghrelin intervention group and PQ group (P < 0.05).</p><p><b>CONCLUSION</b>Ghrelin can up-regulate nuclear expression of Nrf2, increase the activities of HO-1 and NQO1, and reduce the activity of MPO and content of MDA, thus protecting PQ-exposed mice from acute lung injury.</p>

The intervention of baicalin on acute brain injury induced by aconitine in rats and its mechanism / 中国中西医结合急救杂志

Objective To investigate the interference effect of baicalin on acute brain injury induced by aconitine in rats and its mechanism. Methods A total of 200 Sprague-Dawley(SD)rats were randomly divided into five groups:normal control,baicalin control,aconitine poisoning,baicalin 15 mg/kg intervention and baicalin 30 mg/kg intervention groups(each,n=40). Aconitine(20μg/kg)was given via tail vein in aconitine poisoning group. The rats in the normal control group and baicalin control group were respectively injected with saline 2 mL/kg and baicalin 30 mg/kg via tail vein. The aconitine poisoning rats were given with baicalin at the dose of 15 mg/kg and 30 mg/kg respectively in the low and high dose baicalin intervention groups within 2-3 minutes after injection of aconitine. Rats in all groups in the study were anesthetized and sacrificed at 1,6,12,24 hours after various agents were respectively given in the groups,the rat cerebral cortex samples were collected,the histological changes in normal and baicalin control groups and pathological changes of the aconitine poisoning rats were observed,the levels of glutamate(Glu),aspartate(Asp),γ-aminobutyric acid(GABA),glycine(Gly)were detected and the apoptotic cells were determined at the above time points. Results Compared with the normal control group,the aconitine poisoning group had significantly higher levels of excitatory amino acids Glu and Asp and the number of apoptotic neurons. After exposure to aconitine for 1 hour, the levels of inhibitory amino acids of GABA and Gly were markedly decreased in the rat cortex in the poisoning group compared to the normal control group(both P<0.05),at 6 hours and 12 hours they were significantly increased and after 24 h,they began to decline,but still maintained at relatively high levels. Compared with the aconitine poisoning group, after baicalin intervention for 1 hour,in the 15 mg/kg and 30 mg/kg baicalin intervention groups,the levels of Glu and Asp were markedly decreased〔Glu(μmol/L):309.39±14.59,307.22±23.69 vs. 370.46±40.31,Asp(μmol/L):143.43±8.36,129.12±4.86 vs. 222.97±6.26〕,while the levels of GABA and Gly were increased〔GABA(μmol/L):55.91±4.76,59.61±13.11 vs. 32.05±2.20,Gly(μmol/L):32.33±1.85,33.90±0.66 vs. 21.96±4.75〕,and the number of neuronal apoptosis was obviously decreased(cell/mm2:18.65±4.10,14.80±1.89 vs. 58.15±3.68,both P<0.05). Under microscope and electron microscope,the pathological and ultrastructural changes indicated that the aconitine poisoning group had the most marked cerebral cortex damage at 12 hours after poisoning,while the two baicalin intervention groups showed milder damage than that in aconitine poisoning group. Conclusions The neural toxic effect of aconitine in rats may be related to the imbalance between the neurotransmitter contents of excitatory Glu. Asp and inhibitory GABA,Gly in the cerebral cortex. Baicalin can decrease the contents of excitatory amino acid and elevate the inhibitory amino acid,therefore it may ameliorate the cerebral injury of acute aconitine intoxication in rats.

Effects of capsaicin on oxidative stress in lipopolysaccharide-induced acute lung injury in mice / 中华急诊医学杂志

Objective To investigate the effects of transient receptor potential vanilloid 1 activation by capsaicin on the oxidative stress in lipopolysaccharide-induced lung injury in mice in order to elucidate the potential mechanisms.Methods A total of 108 specific pathogen free (SPF) ICR male mice were randomly divided into six groups:normal control group (n =18),capsaicin control group (CAP control group,n =18),capsazepine control group (CAPZ control group,n =18),acute lung injury group (n =18),capsaicin treatment group (CAP treatment group,n =18) and capsazepine treatment group (CAPZ treatment group,n =18).After modeling,superoxide dismutase (SOD),catalase (CAT) and malondiachehyche (MDA) levels in lung were measured with the method of chromatometry,and the expression of heme oxygenase 1 (HO-1) in lung tissue was assessed with enzyme linked immunosorbent assay (ELISA),while the level of NF-E2-related factor-2 (Nrf2) was determined by western blotting and the expression of Nrf2 mRNA was measured by RTPCR.Pathological changes of lung tissue were observed under light microscope.Results The activities of SOD and CAT in lung tissue at 3,8,16 h were dramatically lower in acute lung injury group than those in normal control group (P ＜ 0.05),while the level of MDA was higher.Compared with acute lung injury group,the lung levels of SOD and CAT at 8 h and 16 h were higher in CAP treatment group (P ＜0.05),while the lung level of MDA was lower (P ＜ 0.05).The levels of SOD and CAT in CAPZ treatment group were decreased at 8 h and 16 h,while the levels of MDA in this group were increased at 3,8,16 h (P ＜0.05).The pulmonary levels of HO-1,Nrf2 and expression of Nrf2 mRNA were significantly higher in acute lung injury group than those in normal control group (P ＜ 0.05).Compared with acute lung injury group,the levels of HO-1,NRF2 and expression of NRF2 mRNA were increased markedly in CAP treatment group (P ＜ 0.05)and were obviously decreased in CAPZ treatment group (P ＜0.05).At 8 h,16 h after modeling,the degree of lung damage was ameliorated in CAP treatment group compared with acute lung injury group under light microscope,while the lung damage was aggravated in CAPZ treatment group.Conclusions The activation of TRPV1 could apparently up-regulate the levels of CAT,SOD,Nrf2,HO-1,and reduce the MDA level in lung tissue of mice with acute lung injury,ultimately protecting the endotoxemia mice from oxidative stress.

The intervention effect of Shuanghuanglian on PC12 cell injury induced by aconitine / 中国中西医结合急救杂志

Objective To observe the release of glutamate (Glu)and γ-amino butyric acid (GABA) from PC 12 cells induced by aconitine,and to study the intervention of Shuanghuanglian on the injury of these cells. Methods The cell proliferation test agent in cell counting kit(CCK-8)was applied to assay the aconitine toxicity to PC12 cells and to establish the PC12 cell injury model induced by aconitine. The PC12 cells during logarithmic growing phase were randomly divided into the following groups:blank control group(complete medium containing 0.1% dimethyl sulfoxide was added), Shuanghuanglian control group (complete medium containing 50 μg/mL Shuanghuanglian),baicalin control group(complete medium containing 20 μmol/L baicalin),aconitine toxic group(complete medium containing 100 μmol/L aconitine),Shuanghuanglian intervention group(complete medium containing 100μmol/L aconitine and 50μg/mL Shuanghuanglian)and baicalin intervention group(complete medium containing 100 μmol/L aconitine and 20 μmol/L baicalin). The cells in all groups were incubated for 24 hours respectively. The changes of PC12 cell absorbance(A)values were detected by CCK-8 assay before and after intervention by Shuanghuanglian and baicalin. The PC12 cell apoptosis was determined by flow cytometry. Glu and GABA contents in cell culture medium were determined by chromatometry and enzyme-linked immunosorbent assay (ELISA). Results Compared with blank control group,after the PC12 cells treated with 100 μmol/L aconitine for 24 hours,their cytoactivity was decreased markedly(A value:1.003±0.042 vs. 1.685±0.030,P0.05). Conclusions The changes of Glu and GABA may be one of the mechanisms of neural toxic effect of aconitine. Shuanghuanglian possibly can decrease Glu level and increase GABA content by way of its main component baicalin to antagonize the aconitine neurotoxicity.

Protective effect of capsaicin on lipopolysaccharide-induced activation of vascular endothelial cells / 中国病理生理杂志

AIM:To investigate the effect of capsaicin on lipopolysaccharide ( LPS)-induced activation of cul-tured endothelial cells of mouse aorta in vitro.METHODS:The endothelial cells were isolated from mouse aorta and cul-tured in vitro, and the specific cell markers of the cells were identified by immunofluorescence staining.The cells were stimulated with LPS (100μg/L) combined with or without capsaicin, and the cells and supernatant were collected at 12 h, 24 h and 48 h.The levels of soluble intercellular adhesion molecule 1 ( sICAM-1) , soluble vascular cell adhesion molecule 1 (sVCAM-1) and soluble P-selectin (sP-selectin) in the supernatant were measured by ELISA.The levels of nuclear NF-κB p65 and cytopasmic p-IκBαand IκBαwere detected by Western blotting.RESULTS: Compared with control group, the levels of sP-selectin, sICAM-1 and sVCAM-1 in LPS group were significantly increased (P<0.05), and LPS promoted the expression of sICAM-1 and sVCAM-1 in a time-dependent manner.Compared with LPS group at the same time point, capsaicin inhibited the expression of sP-selectin, sICAM-1 and sVCAM-1 in a dose-dependent manner.Compared with con-trol group, the protein levels of NF-κB p65 and p-IκBαin LPS group at 24 h were significantly increased (P<0.05), while the protein level of IκBαin LPS group at 24 h were significantly decreased (P<0.05).Compared with LPS group, capsaicin decreased the protein levels of NF-κB p65 and p-IκBαand increased the protein level of IκBαin a dose-depend-ent manner.CONCLUSION:Capsaicin has a protective effect on LPS-induced vascular endothelial cell activation, which potentially contributes to the suppression of IκBαdegradation and NF-κB p65 nuclear translocation.

Clinical features and prognosis of patients with vibrio necrotizing fasciitis / 中华创伤杂志

Objective To investigate clinical features,treatments and prognostic factors of the patients with necrotizing fasciitis caused by vibrio infections and thus provide reference for the early treatment and prognostic assessment.Methods A retrospective analysis was conducted on clinical data of 56 patients with vibrio necrotizing fasciitis admitted to the emergency center of our hospital from May 1995 to June 2011.The clinical characteristics and treatments of the patients were summarized,and differences of clinical factors between the survival group and death group were compared.The possible influencing factors for prognosis were also analyzed.Results The main clinical manifestations included fever (61％),shock (84％) and organ dysfunction,of which renal insufficiency (88％) was the most common,with case fatality of 43％.Early pathological changes of limbs were only local swelling and pain,while skin ecchymosis,tension blood blisters,necrosis and subcutaneous crepitation were the signs of advanced stage.Comprehensive treatment regime including early administration of sensitive antibiotics plus surgical incision and drainage and medicine support was given.A series of factors were significantly different between the survival and death groups including the duration from the presentation of symptoms to hospital admission (P ＜ 0.05 ),limb lesions involving the trunk (P ＜ 0.01 ),creatine kinase level (P ＜ 0.05 ),and emergency incision and drainage ( P ＜ 0.01 ).Conclusions The most prominent clinical manifestations of vibrio necrotizing fasciitis are rapidly progressive local symptoms and signs,and sharp deterioration of systemic conditions.Delayed visiting,severe local lesions,and failure to emergency surgery may be the factors for poor prognosis.

Effect of ulinastatin on oxidative stress in the lung tissue of acute H2 S-intoxicated rats / 中华急诊医学杂志

Objective To observe the dynamic changes of heme oxygenase 1,NAD(P)H:quinine oxidoreductase 1 and Nuclear factor-E2-related factor 2 in the lung tissue of acute H2S-intoxicated rats and intervention effects of ulinastratin(UTI).Methods A total of 96 SD rats of clean grade were divided randomly(random number)into four groups:normal control group(NS group,n =8),UTI control group(UTI group,n =8),H2S-intoxicated model group(H2S group,n =40,rats were exposed to H2S(200 × 10-6)for 1 h to establish the H2S-intoxicated model)and UTI treatment group(H2S +UTI group,n =40,rats were intraperitoneal injected with the dose of UTI 105 U/kg).H2S group and H2S + UTI group were sacrificed 2,6,12,24 and 48 h after modeling.The activity and mRNA expression of HO-1 and NQO-1 in the lung tissue were measured by ELISA and RT-PCR methods,and the expression of Nrf2 mRNA and protein in the lung tissue was detected by RT-PCR and Western Blot methods.Pathological changes of lung tissue were observed by lightmicroscope and the lung injury score was used to evaluate inhalation injury.Results The pulmonary HO-1 activity and mRNA expression in rats of H2S group at 2,6,12 h(P ＜ 0.01)after intoxication were markedly increased than that in NS group:In comparison with H2S group,the pulmonary HO-1 activity and mRNA expression increased at 6,12,24,48 h(P ＜0.01).The pulmonary NQO-1 activity and mRNA expression in rats of H2S group at 2,6,12,24 h(P＜ 0.01)after intoxication were markedly increased than that in NS group; In comparison with H2S group,the pulmonary NQO-1 activity and mRNA expression increased at 6,12,24,48 h(P ＜ 0.01).The pulmonary Nrf2 mRNA and protein expression in rats of H2S group at 2,6,12 h(P ＜0.01 or P ＜0.05)after modeling were markedly increased than that in NS group and reached peak 2 hour after modeling; In comparison with H2S group,the pulmonary Nrf2 mRNA and protein expression increased at 6,12,24,48 h(P ＜0.01).At 24 h after modeling,the degree of lung damage were also decreased in H2S group compared with H2S + UTI group in the lightmicroscope.Histopathological examination showed that the degree of lung injury in H2S + UTI group was less severe than that in H2S group especially in the 12,24 and 48 h (P ＜0.01).Conclusions HO-1,NQO-1 and Nrf2 are involved in the pathogenesis of acute lung injury induced by H2S-intoxicated in rats.UTI may improve the imbalance in redox and activate HO-1,NQO-1 and Nrf2 can reduce lung injury and protect the lung injury induced by H2S in rats.