UCP2 Overexpression Affects Mitochondrial Dynamics And Protects Mycardial Mitochondrial Function In Septic Rats

Objective: To investigate the effects of UCP2 overexpression on mitochondrial dynamics(Drp1,Opal,Fis1 protein expression)and mitochondrial function in sepsis-induced myocardial injury by establishing an animal model of sepsis-induced myocardial injury.To explore the potential protective mechanism of UCP2 overexpression in vivo myocardial mitochondria levels of sepsis-induced myocardial injury.Method:Forty SD male rats were randomly divided into 4 groups: Control group(false CLP group),Sham group(false transfection group),AAV group(adeno-associated virus transfection group),UCP2 group(UCP2 overexpression group).Establishment of a rat model of sepsis-induced myocardial injury by CLP.Echocardiography was used to detect cardiac function in rats,and Elisa was used to detect myocardial injury to identify a model of sepsis induced myocardial injury.UCP2 overexpression in heart was achieved by adenoassociated virus.The expression of UCP2 was detected by Western blot in myocardial tissue.UCP2 transfection observed by fluorescence microscope.Ultrastructure of myocardial mitochondria was observed by electron microscopy,ROS production was detected by DHE,ATP production was detected by ATP kit.Western blot was used to detect the expression of Drp1,OPA1 and FIS1 related proteins in myocardial tissue.Result: 1.After establishing CLP model,LVAWd,LVAWs,LVPWd,LVPWs,LVEF and LVFS of rats were significantly increased(P<0.05).LVIDd,LVIDs,LVESV,and LVEDV were significantly decreased(P<0.05).The levels of IL-6,TNF-α,CK,CTn-I and LDH increased significantly(P<0.05),and the symptoms of sepsis appeared in rats.The sepsis model was established successfully.2.The level of UCP2 protein in UCP2 group was significantly higher than that in the other three groups(P<0.05),and green fluorescence was observed.The UCP2 overexpression model was successfully established.3.Compared with Sham group and AAV group,the UCP2 overexpression group showed a decrease in LVAWs、LVEF and LVFS(P<0.05),an increase in LVIDs and LVESV(P<0.05),an increase in IL-6,TNF-α,CK,CTn-I and LDH(P<0.05),an improve in mitochondrial ultrastructure,an increase in ROS production(P<0.05),and an increased in ATP production(P<0.05).4.There was no significant difference in the expression levels of Opa1 and Fis1 protein in myocardial tissue samples of four groups(P>0.05).After establishing the CLP model,the expression level of Drp1 protein in Sham group and AAV group were significantly higher than that in Control group(P<0.05).After UCP2 overexpression,the expression level of Drp1 was lowe(P<0.05).Conclusion: 1.UCP2 overexpression can improve myocardial contractile dysfunction in sepsis;2.Overexpression of UCP2 can ameliorate mitochondrial dysfunction in sepsis myocardial injury 3.UCP2 overexpression reduces ROS production,reduces the level of Drp1 protein,inhibits mitochondrial division,regulates mitochondrial dynamics,improves mitochondrial function,and plays a role in myocardial protection.