Effects of Ivabradine on Lipid Metabolism,Myocardial Fibrosis,and miR-128-3p Level in Rats with Coronary Heart Disease
CHEN Lu
PANG Na
SHANG Yanting
WANG Jingrui
Abstract：Objective:To investigate the effects of ivabradine on lipid metabolism,myocardial fibrosis,and miR-128-3p level in rats with coronary heart disease.Methods:Seventy-two healthy adult Sprague-Dawley rats without specific pathogen(SPF)grade were randomly divided into control group,model group,ivabradine low-dose group,ivabradine medium-dose group,ivabradine high-dose group,and rosuvastatin group,with 12 rats in each group.Coronary heart disease models were established except the control group.After modeling,ivabradine low-dose,medium-dose,and high-dose groups were given gavage of 5,10,20mg/kg ivabradine,rosuvastatin group was given 10 mg/kg rosuvastatin,control group and model group were given equal volume of normal saline,respectively.Color Doppler ultrasonography was used to detect cardiac function.Automatic biochemical analyzer to detect blood lipid index.The degree of myocardial fibrosis was detected by Sirius red staining.The positive cell rates of Collagen Ⅰ and Collagen Ⅲ were detected by immunohistochemistry.Real-time fluorescence quantitative polymerase chain reaction(qPCR)was used to detect the mRNA expression of miR-128-3p and transforming growth factor(TGF-β1)in myocardial tissue.Results:Compared with the control group,the levels of left ventricular end-diastolic volume(LVEDV)and end-systolic volume(LVESV)in model group increased,and the levels of stroke volume(SV)and left ventricular ejection fraction(LVEF)decreased(P＜0.05).Compared with model group,the levels of LVEDV and LVFSV in low-dose,medium-dose and high-dose ivabradine groups decreased,and the levels of SV and LVEF increased(P＜0.05).There was no significant difference between ivabradine high-dose group and rosuvastatin group(P＞0.05).Compared with the control group,the levels of total cholesterol(TC),triglyceride(TG),low density lipoprotein cholesterol(LDL-C),myocardial Collagen volume fraction(CVF)percentage,Collagen Ⅰ,Collagen Ⅲpositive cell rate,and TGF-β,mRNA expression in the model group increased,high density lipoprotein cholesterol(HDL-C)and miR-128-3p decreased(P＜0.05).Compared with model group,the levels of TC,TG,LDL-C,myocardial CVF percentage,Collagen Ⅰ and Ⅲ positive cell rates,and TGF-β,mRNA expression of ivabradine in low-dose,medium-dose and high-dose groups decreased,while HDL-C and miR-128-3p increased(P＜0.05),the difference between low,medium and high dose groups was statistically significant(P＜0.05),there was no significant difference between ivabradine high-dose group and rosuvastatin group(P＞0.05).The results of Sirius red staining showed that the collagen fibers were red,the collagen fibers in the myocardium of rats in the control group were evenly distributed and neatly arranged,while the collagen fibers in the myocardium of rats in the model group significantly increased,disordered and the thick collagen fibers misarranged into a network.There were more myocardial collagen fibers in ivabradine low and medium dose groups,and some collagen fibers interlaced with each other.Myocardial collagen fibers in ivabradine high-dose group and rosuvastatin group reduced,arranged more neatly,and collagen fibers gathered into bundles.Conclusion:lvabadine can improve blood lipid disorders,reduce CollagenⅠ and Collagen Ⅲ levels and inhibit myocardial fibrosis in rats with coronary heart disease.The mechanism may be related to the downregulation of miR-128-3p expression.
Keywords：coronary heart diseaseivabradinemyocardial fibrosismiR-128-3prat
Publication Date：2025-03-15
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：8( 697-704 )