Inhibition of TRAF6 ameliorates myocardial inflammatory injury and cardiac dysfunction via regulating cardiomyocyte inflammation in sepsis mice / 实用医学杂志

ABSTRACT

Objective To explore the effects of TRAF6 inhibition on autophagy,myocardial inflammation and cardiac function in septic mice.Methods Twenty-four male Kunming mice were randomly divided into 4 groupssham,sham + C25-140(sham+C),cecal ligation and puncture(CLP),and cecal ligation and puncture+C25-140(CLP+C)group.Sham+C group and CLP+C group were intraperitoneally injected with C25-140 after operation.LVEF and LVFS were evaluated by ultrasound 24 hours after operation.Serum TNF-α and IL1-β were measured by ELISA.HE staining was used to evaluate myocardial inflammatory response.Autophagosomes and mitochondrial microstructure of cardiomyocytes were observed by transmission electron microscopy.TRAF6 mRNA in myocardial tissue was detected by qPCR.The expression of TRAF6,P62,Beclin-1 and LC3B protein was detected by W-B.The effect of C25-140 on myocardial injury in the septic mice was observed by inhibiting autophagy with 3-MA.Results Compared with the sham group,the levels of TRAF6 mRNA and TRAF6 in the myocardial tissue in the CLP group were significantly increased(P<0.05)and the serum TNF-α and IL1-β concentrations were signifi-cantly increased(P<0.05).Meanwhile,the myocardial tissue HE staining showed inflammatory cell infiltration and the LVEF and LVFS levels were significantly decreased in the CLP group(P<0.05).Compared with CLP group,the CLP+C group showed that the expression of TRAF6 mRNA and TRAF6 protein decreased(P<0.05),serum TNF-α and IL1-β decreased(P<0.05),myocardial histopathological myocardial inflammatory cell infiltration decreased,the LVEF and LVFS levels increased(P<0.05).Electron microscopy showed that the mitochondrial swelling decreased,autophagosomes increased,expression of Beclin-1 and LC3Ⅱ/Ⅰ increased,and P62 expression decreased(P<0.05).As compared with CLP+C group,the CLP+C+3-MA group showed that obvious inflamma-tory cell infiltration in the myocardial pathology and the LVEF and LVFS levels decreased after 3-MA inhibited autophagy(P<0.05).Conclusion Inhibition of TRAF6 can not only ameliorate myocardial inflammatory injury and cardiac dysfunction in septic mice,but promote the involvment of cardiomyocyte autophagy in provention from sepsis-induced myocardial injury.