| Objective:To investigate the protective effect of rapamycin blocking mTOR/p70S6 K pathway on myocardial injury in septic rats.Methods: Ninety rats were randomly divided into three groups:(sham group,sepsis group,rapamycin treatment group),30 rats in each group,A mouse model of sepsis was established with CLP.The Sham group and CLP group were given placebo 2 mg/Kg every 12 hours.For the RPM group,rapamycin was given at 2 mg/Kg half an hour before surgery,and then rapamycin was given at 2 mg/Kg at 12-hour intervals;6 rats were sacrificed in each group 6 hours,12 hours,24 hours,72 hours,and 120 hours,collecting blood and measuring cTnI and CK-MB content;Ventricular intubation to measure cardiac function and hemodynamics in rats at different times,removing cardiac tissues.The concentrations of TNF-?,IL-6,IL-10 in myocardium were determined by enzyme linked adsorption(ELISA).Glutathione peroxidase(GSH-Px)activity was determined by enzymatic reaction glutathione consumption method.The activity of superoxide dismutase(SOD)was determined by xanthine oxidase method.Determination of malondialdehyde(MDA)by thiobarbital acid method.Detecting the changes of mTOR and ribosomal protein S6 kinase(P70S6K)expression in myocardial tissue by Western Blot.Results: 1.Pathological comparison of myocardial tissue injury in three groups of rats:In the Sham group,the myocardial structure was normal;in the CLP group,myocardial tissue were obviously damaged,including a large number of inflammatory cells infiltration,myocardial cell congestion,edema,and even muscle fiber rupture.However,there was also myocardial damage in the RPM group,but the degree of damage was less than that in the CLP group.2.Comparison of cardiac function in three groups of three groups of rats: the heart rate of CLP group increased significantly from 6 to 24 h than Sham group.Compared with the CLP group,the heart rate of the RPM group decreased significantly from 6 to 24h(P<0.05).Compared with Sham group,blood pressure in CLP group decreased significantly from 6 to 24h(P<0.05).Compared with the CLP group,the blood pressure in the RPM group increased significantly from 12 to 24h(P<0.05).Comparing the Sham group with CLP group,the +dp/dtmax in CLP group decreased significantly at 6 ?24h(P<0.05),while the RPM group increased significantly at 6 ? 12h+dp/dtmax compared with the CLP group(P<0.05).Compared with sham group,the-dp/dtmax in CLP group significantly decreased 6-24h(P<0.05),while the-dp/dtmax RPM group significantly increased 6-12 h compared with CLP group(P<0.05).The contents of cTnI and CK-MB in the CLP group were significantly higher than that in the sham group(P<0.05),while the contents of cTnI,CK-MB in the RPM group were lower than those in the CLP group(P<0.05).3.The contents of TNF-? and IL-6 in the three groups were significantly higher in the CLP group than in the sham group(P<0.05),while the contents of TNF-? and IL-6 in the RPM group were significantly lower than those in the CLP group(P<0.05);The contents of IL-10 in the three groups were higher in the CLP group than in the Sham group(P<0.05),while the contents of IL-10 in the RPM group was significantly higher than that in the CLP group(P<0.05).4.Comparison of serum GSH-Px activity,serum SOD activity and MDA content in the three groups: the serum GSH-Px and SOD activity in the CLP group was significantly lower than that in the Sham group(P<0.05),while the serum GSH-Px and SOD activity in the RPM group was significantly higher than that in the CLP group.The serum MDA of the CLP group was significantly higher than that of the Sham group,and the serum MDA of the RPM group was significantly lower than that of the CLP group.5.Compared with the expression of mTOR and p70S6 K in myocardial tissue,the content of mTOR and p70S6 K in CLP group was significantly higher than that in RPM group(P < 0.05).Conclusions: Rapamycin alleviates myocardial damage in septic rats by inhibiting the mTOR/p70S6 K signaling pathway and thereby exerting anti-inflammatory response and oxidative stress injury. |
PDF Full Text Request