| Objective: Myocardial remodeling is the root cause of the development of heart failure after myocardial infarction.In the process of myocardial remodeling,myocardial apoptosis is the main reason for the continuous loss of the units of myocardial contraction,and endoplasmic reticulum stress plays a very important role in myocardial apoptosis.Previous studies have reported that resveratrol(RES)can activate silent information regulator 1(SIRT1)and inhibit endoplasmic reticulum stress(ERS),reduce myocardial apoptosis.In this study,a rat model of myocardial infarction(MI)was established by ligating the anterior descending branch of the left coronary artery。The effect of the Intraperitoneal injection of resveratrol(RES)on cardiac function and myocardial remodeling after myocardial infarction was evaluated in MI rats,and explore its related mechanisms.Methods: The anterior descending branch of the left coronary artery of adult male SD rats was ligated to establish a model of myocardial infarction.Rats that survived within 24 hours were randomly divided into the MI group(n=6)and RES group(n=6).At the same time,there were 5 rats in the control group and 5 inthe sham operation group.The sham operation group was threaded but not ligated under the left anterior descending branch.In the RES group,the dose of intraperitoneal injection of RES is 8mg / kg/ day(resveratrol was previously dissolved in DMSO at a concentration of 16 mg / ml),and the remaining three groups were injected with DMSO at a dose of 0.5ml / kg/ / day.Four weeks after modeling,the left ventricular ejection fraction(LVEF),left ventricular short-axis shortening rate(LVFS),left ventricular end-systolic diameter(LVESD)and left ventricular end-diastole Internal diameter(LVEDD)in each group were measured through echocardiography.Hematoxylin and eosin(H&E)staining and Masson’s staining was adopted to determine the morphological changes in myocardial cells and interstitial fibrosis in each group.Expression of SIRT1 in myocardium was analyzed by immunochemistry.Western blotting was used to detect the expression levels of SIRT1,p-PERK,p-eIF2α,ATF4,CHOP and Caspase3 in myocardium.Apoptosis of cardiomyocyte was observed by TUNEL staining.Results:1.Cardiac ultrasound shows that there was no significant difference in cardiac function between the control group and the sham operation group.Compared with the control group,the LVEF and LVFS of the MI group decreased,while the LVESD and LVEDD of MI group increased compared with the sham operation group.Compared with the MI group,the LVEF and LVFS of the RES group increased,while the LVESD and LVEDD of the RES groupdecreased compared with the MI group.2.The result of HE staining showed that the myocardial cells in the control group and the sham operation group were arranged regularly.Compared with the control group,the myocardial cells in the MI group were sparse and the myocardial fibers were disordered.Compared with the MI group,the myocardial cells in the RES group increased and arranged neatly.3.Masson staining showed that the control group and sham operation group had no obvious collagen fiber deposition.Compared with the control group,myocardial interstitial tissue in the MI group had a large number of collagen fibers deposited.Compared with the MI group,the myocardial interstitial collagen fibers in the RES group were significantly reduced.4.The result of immunochemistry showed that there was no significant difference in the expression of SIRT1 in myocardial tissue between the control group and the sham operation group.Compared with the control group,the expression level of SIRT1 in myocardial tissue in the MI group was increased.Compared with the MI group,the expression levels of SIRT1 in myocardial tissue in the RES group were decreased.5.TUNEL staining results showed that there was no myocardial apoptosis in the control group and sham operation group.Compared with the control group,myocardial apoptosis was significantly increased in the MI group.Compared with the MI treatment group,myocardial cell apoptosis was decreased in the RES treatment group.6.Western blotting results showed that compared with the control group,the expression levels of p-PERK,p-eIF2α,ATF4,CHOP、and caspase3 in myocardial tissue were increased in the MI group(P <0.01),but the expression levels of SIRT1 were decreased(P <0.05).Compared with the MI group,the expression levels of p-PERK,p-eIF2α,ATF4,and caspase3 in myocardial tissue were decreased in the RES group(P <0.01),but the expression level of SIRT1 in the RES group was higher than that of the MI group(P <0.05).Conclusion: Resveratrol can improve cardiac function and myocardial remodeling after myocardial infarction.The mechanism is achieved by up-regulating SIRT1 and inhibiting the PERK endoplasmic reticulum stress pathway to reduce myocardial cell apoptosis. |
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