Effect Of Dexmedetomidine Post-treatment On Myocardial Ischemia/Reperfusion Injury And Its Mechanism

ObjectiveTo investigate the protective effect of DEX post-treatment on myocardial ischemia reperfusion injury in rats and its possible mechanism.in vitro,Hypoxia/reoxygenation model was used to further explore the protective effect of DEX post-treatment on myocardium and its possible mechanism.MethodsFirst,At the cellular level,A model of cardiomyocyte apoptosis induced by hypoxia reoxygenation in primary isolated neonatal rat cardiomyocytes,Divided into normal control group,hypoxia reoxygenation group and DEX post-treatment group,Using the ELISA method to detect the content of CK-MB、c Tn I and CK,TUNEL used to detect apoptosis,weston blot can be used to detect the expression Bax/Bcl2 apoptosis-related proteins,Using ELISA method to detect the TNF-α and IL-6 of inflammatory factors,WST-1detection of ROS expression,TBA detection of MDA.Second,At the animal level,A rat model of acute ischemia-reperfusion injury was constructed by ligation of left anterior descending coronary artery,Divided into normal control group,ischemia-reperfusion group and DEX post-treatment group,Using a multi-channel physiological monitor to record data at each time,The data are as follows: left ventricular diastolic blood pressure(LVDEP),heart rate(HR),coronary flow(CF)and maximum rate of increase/decrease(dp/dtmax,)of indoor pressure-dp/dtmax),Detection of myocardial infarction by TCC staining,Using ELISA methods to detect CK、CK-MB and c Tn I,TUNEL method can be used to detect apoptosis rate,The expression of P38 protein,cleaved Caspase3/Caspase3 ratio and Bax/Bcl2 ratio depend on the detection of weston blot,Using ELISA method to detect the TNF-α and IL-6 of inflammatory factors,WST-1 detection of ROS expression,The content of MDA was detected by TBA method.ResultsIn in vitro study,Dex post-treatment could reduce the contents of CK-MB,c Tn I and CK in rat cardiomyocytes of hypoxic and reoxygenated model group,and the difference was statistically significant compared with the control group(P<0.05).Dex posttreatment also decreased the apoptosis rate,Bax/Bcl2 ratio,cleaved Caspase3/Caspase3 ratio,and the differences were statistically significant compared with the control group(P<0.05).The contents of TNF-α,IL-6 and ROS,MDA were lower than those in the control group,and the difference was statistically significant(P<0.05).It is suggested that DEX post-treatment can reduce inflammatory response and oxidative stress.Further study showed that the expression of P38 protein in the DEX pretreatment group was significantly lower than that in the control group,with statistical significance(P<0.05).In in vivo study,After DEX treatment,the area of myocardial infarction in rats with myocardial ischemia/reperfusion injury was decreased,CFandthe maximum rate of indoor pressure(+dp/ dtmax)was significantly increased compared with the control group,while LVDEP was significantly decreased compared with the control group,the difference was statistically significant(P<0.05).The contents of CK-MB,c Tn I and CK were significantly decreased compared with the control group,and the difference was statistically significant(P<0.05).Dex posttreatment also decreased the apoptosis rate,Bax/Bcl2 ratio,cleaved Caspase3/Caspase3 ratio,and the differences were statistically significant compared with the control group(P<0.05).The contents of TNF-α,IL-6 and ROS were lower than those in the control group,and the difference was statistically significant(P<0.05).It is suggested that DEX post-treatment can reduce inflammatory response and oxidative stress.Further study showed that the expression of P38 protein in the DEX post-treatment group was significantly lower than that in the control group,with statistical significance(P<0.05).ConclusionsDex post-treatment protects cardiomyocytes against apoptosis,inflammation and oxidative stress by activating the P38 signaling pathway,and alleviates heart ischemia-reperfusion injury to protect cardiac function.