The Value Of Expression Changes Of ELP2,STAT3 And P-STAT3 In Myocardial Fibrosis Induced By Angiotensin Ⅱ

Objective:In this study,we investigated the expression changes of elongator factor complex subunit 2(ELP2),signal transducers and activators of transduction 3(STAT3)and phosphorylated STAT3(P-STAT3)in angiotensin Ⅱ(Ang Ⅱ)-induced myocardial fibrosis model in mice,as well as the changes of various indicators after addition of valsartan.To explore the role of ELP2 and STAT3 signaling pathways in the formation of myocardial fibrosis.Methods:1)Establishment of myocardial fibrosis model:Mice were randomly divided into control group,model group and valsartan group,and their basal body weight(BW),systolic blood pressure(SBP)and heart rate(HR)were measured.Cardiac output(CO),diastolic left ventricular diameter(LVEDd),systolic left ventricular diameter(LVEDs),left ventricular ejection fraction(EF),left ventricular shortening fraction(FS),stroke volume(SV),diastolic left ventricular volume(LVEVd),systolic left ventricular volume(LVEVs)were detected by ultrasound.Mice were implanted with microosmotic pump,which were as follows:control group:micropump continuously pumped normal saline 1.44ug/g/d+feeding water;Model group:1.44ug/g/d AngⅡ solution+feeding water was continuously pumped by micropump;In the valsartan group,1.44ug/g/d AngⅡ solution was continuously pumped by micropump and 40ug/g/d valsartan solution was intragastally administered.After 2 weeks,BW,SBP,HR and cardiac ultrasound indexes of mice were measured.The mice were sacrificed and stained with Skywolf scarlet to observe the changes of collagen staining area in each group.2)Related protein and mRNA expression levels:The protein expression levels of typeⅠ collagen(COL1A1),type Ⅲ collagen(COL3A1),ELP2,STAT3 and P-STAT3 in cardiomyocytes of mice in each group were detected by immunofluorescence and Western Blot.QPCR was used to detect the mRNA expressions of COL1A1,COL3A1,ELP2 and STAT3 in myocardial cells of mice in each group.Results:1)Before and after modeling,there were no statistical differences in BW,SBP,HR,CO,LVEDs,EF,FS,SV and LVEVs among the three groups(P>0.05).After 2 weeks,compared with the control group,LVEDd and LVEVd in model group were significantly decreased,collagen fibers were significantly increased and the color was red,collagen staining area was significantly increased,COL1A1 protein,COL3A1 protein and mRNA expression were significantly increased,the differences were statistically significant(P<0.05).COL1A1 mRNA expression was increased,and there was no statistical significance(P>0.05).2)Compared with the control group,the expressions of ELP2,STAT3 and P-STAT3 proteins in the model group were increased,and the expressions of ELP2 protein and mRNA,STAT3 mRNA and p-STAT3/STAT3 protein were significantly up-regulated,with statistical significance(P<0.05).3)Compared with model group,myocardial tissue section staining of mice in valsartan group showed decreased collagen fiber precipitation,lighter color,significantly decreased collagen staining area,and significantly down-regulated COL1A1 protein,COL3A1 protein and mRNA expression,with statistical significance(P<0.05).But there was no statistical significance in COL1A1 mRNA downregulation(P>0.05).The expressions of ELP2,STAT3 and P-STAT3 protein were decreased in the valsartan group,and the expressions of ELP2 protein and mRNA,STAT3 mRNA and p-STAT3/STAT3 protein were significantly downregulated,with statistical significance(P<0.05).Conclusion:(1)The modeling method of myocardial fibrosis induced by Ang Ⅱ in mice has high feasibility.(2)During the formation of myocardial fibrosis,the STAT3 pathway is activated and ELP2 is involved.(3)Valsartan can inhibit Ang Ⅱ-induced myocardial fibrosis to a certain extent.