| Myocardial ischemia-reperfusion injury(MIRI),which is the recovery of blood supply after myocardial ischemia for a period of time,causes additional cell death,aggravates myocardial dysfunction and structural damage,and further damages of myocardial tissue pathophysiological phenomena of irreversible damage.Studies have shown that paeoniflorin has anti-inflammatory,anti-oxidative free radical damage,regulate immune function,inhibit intracellular calcium overload,reduce blood viscosity,anti-platelet aggregation,dilate blood vessels and other biological activitie.And paeoniflorin can be anti-oxidation,anti-apoptosis,neuroprotection and other methods play a role in the prevention of ischemia-reperfusion injury,but the above research mainly focuses on brain tissue,and there are few studies on perfusion injury of myocardial ischemia,and the research is not deep enough.Therefore,this subject conducts in-depth research on the pharmacological action and mechanism of paeoniflorin anti-MIRI,in order to reveal the target of paeoniflorin to protect the myocardium,and provide a basis for the further development of paeoniflorin.The contents of the paper are summarized as follows:1.The protective effect of paeoniflorin pretreatment on MIRI in ratsThe rat left anterior descending coronary artery was ligated,myocardial ischemia was performed for 30 min,and reperfusion was performed for 120 min.The rat model of MIRI was established and the rats were pretreated with drugs.The experiment was divided into 6 groups,sham operation group(sham group),model group(I/R group),diltiazem hydrochloride group(DLZ group: 30 mg/kg),and paeoniflorin low dose group(PF1 group: 30 mg/kg).,paeoniflorin middle dose group(PF2 group: 60 mg/kg),paeoniflorin high dose group(PF3 group: 120mg/kg).Abdominal aorta blood was collected 120 min after reperfusion,and the changes of myocardial enzyme indexes(AST,CK,CK-MB,LDH)and antioxidant indexes(SOD,MDA,GSH-Px,CAT,NO)in serum were detected.Myocardial infarct size was detected by Evans blue and TTC staining,and the morphology of myocardial tissue was examined by H&E staining.The protective effect of paeoniflorin pretreatment on rat MIRI was investigated.The result showed that paeoniflorin can reduce the activity of myocardial enzymes(AST,CK,CK-MB,LDH)to different extents,significantly reduce infarct size,improve myocardialhistopathological morphology,and increase oxygen free radical scavengers(SOD,GSH-Px,CAT,NO),and decrease the content of MDA in a dose-dependent manner,and the high dose of paeoniflorin(120 mg/kg)was the most effective.2.Effect of paeoniflorin pretreatment on apoptosis and autophagy in rat MIRI cellsGrouping and administration as above,myocardial tissue was collected immediately after reperfusion for 120 min.The related protein of apoptosis(bax,caspase-3,bcl-2)and autophagy(LC3B,beclin-1,cathepsin B)in myocardial tissue were detected by Western blot.The rate of apoptotic expression was detected by TUNEL,transmission electron microscopy to examine the ultrastructure of myocardial tissue.Further study on the regulation of paeoniflorin preconditioning on apoptosis and autophagy in MIRI.The result showed that paeoniflorin can reduce the levels of proapoptotic genes bax and caspase-3,up-regulate the expression of anti-apoptotic gene bcl-2,decrease the apoptosis rate of cardiomyocytes.And it also down-regulate the level of autophagy-related protein beclin-1,regulate the levels of LC3 II and cathepsin B,enhancing lysosomal function,improving myocardial ultrastructure and reducing mitochondrial autophagyin a dose-dependent manner,paeoniflorin high dose(120 mg / kg)was the most significant effect.In conclusion,paeoniflorin can reduce myocardial ischemia-reperfusion injury and protect myocardial tissue to some extent by reducing myocardial enzyme activity,anti-oxidation,inhibiting apoptosis and autophagy to improve myocardial cell survival rate,and the results provide a basis for further study of paeoniflorin. |
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