Rosiglitazone On Sepsis In The Rat Lung Tissue Tlr4 And Stat3 Activity And Its Mechanism Is Discussed In This Paper

Objective To observe the effects of rosiglitazone, an agonist of peroxisomeproliferator-activated receptor γ (PPARγ), on pulmonary injury in septic rats inducedby cecal ligation puncture and explore the possible mechanism.Methods Forty-eight healthy male Wistar rats were randomly divided into3groups:sham group(group SHAM); cecal ligation puncture group(group CLP); rosiglitazonegroup(group ROSI): rats were intravenous injected with rosiglitazone0.3mg/Kg0.5hbefore CLP．Eight rats were sacrificed at6and24h after CLP respectively in eachgroup. Blood was reserved for the measurement of the level of plasma TNF-α andIL-6by ELISA and lung tissues were removed for the detections of lung wet/dry ratio,lung myeloperoxidase(MPO) activity, lung tissue HMGB1mRNA and TLR4mRNAexpression by real-time PCR.Results Compared with group SHAM, the lung W/D ratio, MPO activity, plasmaTNF-α level, IL-6level, HMGB1mRNA and TLR4mRNA expression weresignificantly increased in group CLP and group ROSI (P<0.05). Compared withgroup CLP, the lung W/D ratio, MPO activity, plasma TNF-α level, IL-6level, thelung tissue HMGB1mRNA and TLR4mRNA expression expression weresignificantly decreased in group ROSI (P<0.05).Conclusion Rosiglitazone can decrease the plasma TNF-α level, IL-6level andHMGB1mRNA expression level and inhibit the inflammatory cascade reaction. Itcan reduce the lung tissue neutrophil infiltration. So it can attenuate the pulmonaryedema and inflammation in septic rats by CLP. It can have protective function on pulmonary injury. The possible mechanism may be related to inhibit TLR4expresion. Objective To observe the effects of rosiglitazone, an agonist of peroxisomeproliferator-activated receptor γ (PPARγ), on TLR4and STAT3expression in septicrats with pulmonary injury induced by cecal ligation puncture and discuss thepossible mechanism.Methods One hundred and twenty healthy male Wistar rats were randomly dividedinto5groups: sham group(group SHAM); cecal ligation puncture group(group CLP);rosiglitazone group(group ROSI): rats were intravenous injected with rosiglitazone0.3mg/Kg30min before CLP; GW9662and rosiglitazone group(groupGW+ROSI):rats were intravenous injected with GW96620.3mg/Kg30min beforeCLP and then rosiglitazone0.3mg/Kg15min before CLP; rapamycin group(groupRPM): rats were subcutaneously injected with rapamycin0.4mg/Kg30min beforeCLP; Eight rats in each group were served for survival analysis．Eight rats weresacrificed at6and24h after CLP respectively in each group. Blood was reserved forthe measurement of the level of plasma TNF-α and IL-6by ELISA and lung tissueswere removed for the detections of lung wet/dry ratio, lung myeloperoxidase(MPO)activity, signal transducer and activator of transcription3(STAT3) DNA bindingactivity and lung tissue HMGB1mRNA and TLR4mRNA expression by real-timePCR.Results Compared with group SHAM, the lung W/D ratio, MPO activity, plasmaTNF-α level, IL-6level, STAT3DNA binding activity and HMGB1mRNA and TLR4mRNA expression were significantly increased in group CLP, group ROSI,group RPM and group GW+ROSI (P<0.05). Compared with group CLP and groupGW+ROSI respectively, the lung W/D ratio, MPO activity, plasma TNF-α level, IL-6level, the lung tissue HMGB1mRNA expression and TLR4mRNA expression weresignificantly decreased in group ROSI and group RPM (P<0.05).Conclusion Rosiglitazone can inhibit TLR4expression, decrease the plasma TNF-αlevel, IL-6level and and HMGB1mRNA expression level, so as to inhibit the lungtissue STAT3DNA binding activity and attenuate the pulmonary edema andinflammation in septic rats by CLP. It can have protective function on pulmonaryinjury.