| Objective: This study observed the effects of Melatonin on myocardial remodeling and cardiac function after myocardial infarction in rats,and explored whether its mechanism is related to the regulation of PKM2/STAT3 signaling pathway.Methods:32 adult male Sprague-Dawley(SD)rats were randomly designed to be divided into 4 groups: blank control group(Control group),sham operation group(Sham group),operation group(MI group),operation + melatonin administration Group(MI+Melatonin group).The rat model of myocardial infarction in the left anterior descending branch of the coronary artery was surgically ligated.The rats in the surgery +melatonin administration group were treated with melatonin,and melatonin(50mg/kg/d)was injected intraperitoneally every day.fter 4weeks of rearing,the left ventricular ejection fraction(LVEF),left ventricular fractional shortening(LVFS),and left ventricular end systolic diameter were measured by echocardiography.(Left ventricular end-systolic diameter,LVESD),left ventricular end diastolic diameter(LVEDD)and left ventricular end-systolic diameter(LVEDD),and left blood samples of SD rats in each group.The blood samples used ELISA kit and ELisa method to detect the content of adenosine triphosphate(ATP)and lactic acid in SD rats.The morphological changes of the myocardial tissues of the four groups of rats were observed by HE staining,the changes of myocardial fibrosis in the four groups of rats were observed by Masson staining,the myocardial infarction area of the four groups of rats was detected by TTC staining,and then the TUNEL method was used to detect the four groups of rats The apoptosis of myocardial cells was detected by immunohistochemistry for the expression of PKM2 in the myocardial tissues of the four groups of rats,and the localization and expression of PKM2,STAT3,IL-6,and IL-1β in the myocardium of the four groups of rats were detected by immunofluorescence.Results:1.The results of cardiac ultrasound showed that there was basically no significant difference between the LVEF,LVFS,LVESD and LVEDD values of SD rats in the blank control group and the sham operation group.The LVEF and LVFS values of SD rats in the operation group and the operation + melatonin drug group were lower than the blank control group(P<0.01),while the LVESD and LVEDD values of the SD rats in the operation group and the operation + melatonin drug group were blank The increase in the control group(P<0.01)indicates that the heart function of rats after coronary artery ligation has become worse.The LVEF and LVFS values of SD rats in the surgery + melatonin drug group were higher than those in the surgery group(P<0.01).The LVESD and LVEDD values of SD rats in the surgery + melatonin drug group were lower than those in the surgery group,suggesting melatonization After being treated with vitamins,it can improve the cardiac function of rats with myocardial infarction to a certain extent.2.The results of HE staining showed that in the blank control group and the sham-operated group of SD rats,the gap between the rat’s cardiomyocytes and the cardiomyocytes was small,and the cardiomyocyte envelopes were intact and arranged neatly together,very tightly and regularly.In the SD rats in the operation group,the arrangement of myocardial cells was sparse and the arrangement of myocardial fibrous tissue was chaotic.There was a large amount of fibrous tissue proliferation in the myocardial interstitium.Compared with the surgery group,the SD rats in the surgery + melatonin drug group arranged better cardiomyocytes,and the degree of myocardial fibrosis changed less.3.The results of Masson staining show that: it can be clearly seen that there is no obvious collagen fiber deposition and no obvious fibrosis in the interstitium of the myocardial tissue of SD rats in the blank control group and the sham operation group.Compared with the blank control,SD rats in the operation group had more blue-stained parts in the myocardial tissue interstitium,and the collagen volume fraction(CVF)increased significantly(P﹤0.01).Collagen fibers are deposited,and there are obvious fibrotic changes in the interstitium of myocardial tissue.Compared with the operation group,SD rats in the operation + melatonin drug group had less blue staining in the interstitium of myocardial tissue,indicating that the deposition of collagen fibers was reduced,and the collagen volume fraction(CVF)was significantly lower(P<0.01),suggesting the administration of melatonin The degree of myocardial fibrosis in SD rats with melanin was improved.4.The results of TC staining showed that the myocardial tissue of SD rats in the blank control group and the sham operation group was basically red,and there was no obvious infarct area.The non-infarcted area(red)and the infarcted area(white)of SD rats in the operation group were clearly demarcated,indicating that the SD rats had a successful MI operation.Compared with the blank control group,SD rats in the operation group showed a larger central infarct area of myocardial tissue and a significant increase in the area of myocardial infarction(P<0.01).Compared with the operation group,SD rats in the operation+drug group had a smaller central infarct area of myocardial tissue,and the area of myocardial infarction was significantly reduced(P<0.01).5.The results of TUNEL method showed that there was no cardiomyocyte apoptosis in SD rats in the blank control group and sham operation group.There are more green parts in the myocardial tissue of SD rats in the operation group than in the blank control group,suggesting that the apoptosis of myocardial cells in this group is obvious;The green part of the myocardial tissue of SD rats in the operation+drug group was less than that of the rats in the operation group,suggesting that the apoptosis of myocardial cells in rats was reduced after melatonin was administered.6.The results of immunohistochemistry showed that there was basically no difference in the expression of PKM2 in SD rats between the blank control group and the sham operation group.The expression of PKM2 in the myocardial tissue of SD rats in the operation group was higher than that in the blank control group(P<0.01);the expression of PKM2 in the myocardium of SD rats in the operation + drug group was lower than that in the operation group(P<0.01).7.ELISA test results: the concentration of ATP and lactic acid in the heart blood of the four groups of SD rats had no significant difference,and no statistical significance.8.The immunofluorescence results showed that the expression levels of PKM2,STAT3,IL-1β,and IL-6 in SD rats in the blank control group and the sham operation group were lower than those in the operation group.On the contrary,the expression of PKM2,STAT3,IL-1β and IL-6in the myocardial tissue of SD rats in the operation group increased(P<0.01);after treatment with melatonin,PKM2,STAT3,IL-1β,and IL-6in the myocardial tissue of SD rats with myocardial infarction The expressions of STAT3,IL-1β,and IL-6 all decreased(P<0.01).Conclusion:Melatonin improves myocardial remodeling after myocardial infarction in rats,which may be related to the down-regulation of the expression of PKM2/STAT3 signaling pathway. |
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