Study On The Protective Effect And Mechanism Of Qianghuo Alcohol On Myocardial Infarctio

Purpose:To investigate the protective effect and mechanism of notopterol on mice with myocardial infarction.Material and method:A total of 103 male C57 mice at 7-8 weeks were selected and fed for 2 weeks under normal conditions(22℃,12 h light /12 h dark cycle).LDA method was used to establish myocardial infarction model(MI)in mice.The mice were randomly divided into the following groups: 1)sham operation group(n=12);2)Model group +(5%DMSO+95%CMC-Na)solution group(n=20);3)Model group + notopterol 10mg/kg group(n=20);4)Model group +notopterol 30mg/kg group(n=20);5)Model group +notopterol 100mg/kg group(n=20).On this basis,in order to explore the time point of effect of notopterol on myocardial infarction,each group was divided into two time points: early administration(0.5h postoperative intragastric administration)and delayed administration(12h postoperative intragastric administration).They were given intragastric administration at0.5h and 12 h postoperatively,and were killed after 28 days of continuous administration.On the 14 th and 28 th day of continuous administration,cardiac ultrasound was used to detect the effect of notopterol on cardiac function of myocardial infarction mice,and the optimal dose of notopterol was determined;The weight ratio of heart,liver,lung and kidney in mice was measured to detect the effect of notopterol on viscera;Blood was collected from orbit of mice,The hepatorenal toxicity of notopterol was evaluated by alanine aminotransferase(ALT),aspartate aminotransferase(AST),creatinine(CRE)and urea nitrogen(BUN)indexes;In terms of pathology,HE staining was used to observe the changes of cardiac remodeling,Masson staining was used to observe the changes of myocardial fibrosis,WGA staining was used to observe the changes of myocardial hypertrophy;CD34 To observe the changes of angiogenesis;The expression of myocardial fibrosis(Col1A1,Col1A2,Col5A1,Col5A2,Col3A1,TGF-β)and myocardial hypertrophy(ANP,β-MHC)were detected by fluorescence quantitative PCR(RT-PCR);The phosphorylation of GSK3 β in myocardial tissue of myocardial infarction mice was detected by Western blot(Wb)Results:1.Echocardiography results showed that compared with sham operation group,ejection fraction(FS)and shortening fraction(FS)values in model group were decreased(P<0.05),suggesting that cardiac function of myocardial infarction mice was decreased.Compared with the model group,the ejection fraction(FS)and shortening fraction(FS)values of mice in the notopterol treatment group were increased(P<0.05),suggesting that notopterol can improve the cardiac function of mice with myocardial infarction to some extent.Among them,the effect of 100mg/kg of notopterol group was the most significant2.Echocardiographic results show that,compared with model group,the early delivery and delay for two times,notopterol treatment group mice ejection fraction(FS)and shortening fraction(FS)values were elevated(P<0.05),suggesting notopterol in the two periods of myocardial infarction has the ability to improve cardiac function in mice,and found no significant difference between two time points.3.The results of toxicity test in mice showed that there was no statistical significance in alanine aminotransferase(ALT),aspartate aminotransferase(AST),creatinine(CRE)and urea nitrogen(BUN)after the treatment of notopterol(P>0.05),suggesting that notopterol had no liver and kidney toxicity in myocardial infarction mice.4.The results of HE staining showed that the structure of myocardial tissue could be improved.Masson staining showed that notopterol inhibited collagen deposition.WGA staining showed that the hypertrophy of cardiomyocytes could be improved.CD34 staining showed that notopterol could increase angiogenesis,suggesting that notopterol could improve myocardial remodeling,myocardial fibrosis,myocardial hypertrophy and angiogenesis in myocardial infarction mice to some extent.Meanwhile,it was further verified that notopterol played a role in both early and delayed administration periods,and no significant difference was found between the two time points.5.Fluorescence quantitative PCR(RT-PCR)results showed that compared with sham operation group,the expression levels of Col1A1,Col1A2,Col5A1,Col5A2,Col3A1,TGF-β,ANP,β-MHC were increased in model group(P < 0.05).Compared with model group,the expressions of Col1A1,Col1A2,Col5A1,Col5A2,Col3A1,TGF-β,ANP and β-MHC were decreased in notopterol treatment group(P<0.05).It is suggested that notopterol can inhibit myocardial fibrosis and hypertrophy in myocardial infarction mice.6.Western blot results showed that compared with the model group,p-GSK3/GSK3βratio in the treatment group was increased,suggesting that the phosphorylation of GSK3β(Ser9)in the treatment group was regulated.Conclusion:1.Notopterol can improve the cardiac function of mice with myocardial infarction.The optimal dose was 100mg/kg of notopterol.In addition,the effect was significant at both early and delayed dosing time points,suggesting that notopterol was effective at both time points,but no significant difference was found between the two time points.2.Notopterol can improve myocardial remodeling,fibrosis,hypertrophy and angiogenesis in mice with myocardial infarction.3.The phosphorylated expression of GSK3β(Ser9)was enhanced by notopterol,suggesting that notopterol may play a role in the protective effect of myocardial infarction.