| Purpose:Myocardial infarction(MI)is a prevalent cardiovascular disease defined by myocardial ischemia and hypoxic damage caused by plaque rupture,thrombosis,lumen stenosis,or blockage in the coronary artery.Although,the development of emergency percutaneous coronary interventional therapy has enabled the rapid restoration of blood perfusion to ischemic myocardium and the rescue of dying myocardium cells.Some dying myocardium cells have caused irreversible damage and impaired cardiac function recovery in recent years.Icariin has been utilized to treat various ailments as a natural chemical extract.Icariin is a traditional Chinese medicine frequently used to treat CVD(Cardiovascular disease).Icariin has been shown to protect the cardiovascular system by boosting the expression of Nrf2 and HO-1.This study aims to explore the protective effect of Icariin in cardiac repair and cardiac remodelling with myocardial infarction and to explore the related factors and mechanisms of its effect,which provide experimental basis and theoretical basis for the use of Icariin as a drug for the prevention and treatment of clinical myocardial infarction.Methods:SPF C57BL/6 mice 25±3 gwere used to establish a myocardial infarction model by coronary artery ligation.Mice were divided into three groups(Sham,MI,and Icariin),each with 15 mice.Icariin(60mg/kg)was administered orally for 28 days following dissolving in 0.5percent DMSO(as a single dose/day).The rats in groups I and II were given normal saline,but the mice in group III were given Icariin.Thoracic echocardiography was used to assess cardiac function four weeks after MI mapping.Cardiac function indices such as left ventricular ejection fraction(LVEF%)and left ventricular short-axis shortening(LVFS%)were analyzed to evaluate cardiac structure and function of mices in each group.HE staining was used to observe the pathological damage of myocardial tissue,and Masson staining was performed to evaluate the degree of myocardial tissue fibrosis in each group of mice.qRT-PCR was used to analyzed the mRNA expression of inflammatory factors(IL-1β,TNF-αand IFN-γ)in myocardial tissues;ELISAwas used to detect the inflammatory factor IL-1β,TNF-α and IL-10 in peripheral serum to evaluate the inflammatory response of each group.TUNEL assay was performed to detect apoptosis in cardiomyocytes of each group of mice.The protein levels of HO-1,Nrf2,P38,P-P38,Bcl-2,Bax,Cytochrome c,and cleaved Caspase-3 were detected by Western blot(WB).The alterations of T lymphocyte subsets and its surface costimulatory molecules by using flow cytometry.The H9C2 cells were transfected with HO-1 siRNA and divided into scrambled+MI group,HO-1 siRNA+MI group,scrambled+ICA+MI group,HO-1 siRNA+ICA+MI group.The cell viability was measured by CCK8 assay and caspase-3 activity were also measured,the apoptosis rate was detected by flow cytometry,and the protein levels of Nrf2,HO-1 Bcl-2 and cleaved caspase-3 were detected by Western blot.Results:LVEF and LVFS were significantly lower in the MI group compared with the sham-operated group(P<0.05).LVFS and LVEF data were significantly higher in the MI+ICA group compared with the MI group(P<0.05)Icariside was able to reduce myocardial infarction area in MI mice,and myocardial injury and myocardial fibrosis were improved,while apoptosis of cardiomyocytes was inhibited.Icariin reduced inflammation by reducing the expression of TNF-α,IL-1β,INF-γ and IL-17.CD8+CTL and Th1 cells were lower in the ICA-treated group than in the MI group,and CD3+CD4+Foxp3+Treg cells were elevated.Compared with MI group,The expression of Nrf2 and HO-1 protein and mRNA were increased in MI+ICA group.Compared with MI+ICA group,H9C2 cell viability was decreased,the apoptosis rate was increased,Caspase-3 activity and cleaved caspase-3 protein level were increased in HO-1 siRNA+MI+ICA group(P<0.05).Conclusion:Icariin can improve early ventricular remodeling after acute myocardial infarction.Icariin can reduce myocardial injury after myocardial infarction by inhibiting inflammation.Icariin inhibits myocardial infarction injury and apoptosis by up-regulating Nrf2/HO-1 signaling pathways. |
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