河南中医2025，Vol.45Issue(10)：1551-1558,8.DOI:10.16367/j.issn.1003-5028.2025.10.0251
柴胡皂苷D调控Wnt/β-catenin信号通路改善慢性心力衰竭大鼠心肌纤维化
Study on Saikosaponin D Improving Ameliorates Myocardial Fibrosis in Rats with Chronic Heart Failure by Regulating the Wnt/β-Catenin Signaling Pathway
摘要
Abstract
Objective:To investigate the effect of saikosaponin D on myocardial fibrosis in rats with chronic heart failure(CHF)and to preliminarily explore its mechanism of action.Methods:A total of 60 SD rats were randomly divided into the control group,the model group,the low-dose saikosaponin D group(25 mg·kg-1),the high-dose saikosaponin D group(50 mg·kg-1),and the high-dose sai-kosaponin D(50 mg·kg-1)+lithium chloride(15 mg·kg-1)LiCl,a Wnt activator)group,with 12 rats in each group.Except the control group,CHF models were established in the other groups by ligating the abdominal aorta.After successful modeling,the rats were treated with corresponding doses of saikosaponin D.The high-dose saikosaponin D+LiCl group received intravenous tail vein injections of 15 mg·kg-1 LiCl for two weeks before modeling.The control and model groups received equivalent volumes of saline via tail vein in-jection and intraperitoneal injection.All treatments were administered for 14 consecutive days.Cardiac function parameters,including left ventricular end-diastolic diameter(LVEDD),left ventricular end-systolic diameter(LVESD),left ventricular ejection fraction(LVEF),and left ventricular short-axis shortening rate(LVFS),were measured using the cardiac function detector.Myocardial tissue pathological damage was observed using HE staining.Myocardial fibrosis was assessed using Masson staining.Cardiomyocyte apoptosis rate was detected using TUNEL staining.The expression levels of α-smooth muscle actin(α-SMA)and collagen Ⅰ(Col Ⅰ)were meas-ured by immunohistochemistry.The protein expression levels of Bax,Caspase-3,β-catenin,and GSK-3β were detected by Western blot.Results:Compared with the control group,the model group showed significantly increased LVEDD and LVESD,decreased LVEF and LVFS,increased cardiomyocyte apoptosis rate and expression levels of Bax,Caspase-3,α-SMA,Col Ⅰ,and β-catenin,and significantly decreased expression of GSK-3β.Compared with the model group,the saikosaponin D treatment groups showed significantly decreased LVEDD and LVESD,increased LVEF and LVFS,reduced cardiomyocyte apoptosis rate and expression levels of Bax,Caspase-3,α-SMA,Col Ⅰ,and β-catenin,and increased expression of GSK-3β.Compared with the high-dose saikosaponin D group,the high-dose sai-kosaponin D+LiCl group showed significantly increased LVEDD and LVESD,decreased LVEF and LVFS,increased apoptosis rate and expression levels of Bax,Caspase-3,α-SMA,Col Ⅰ,and β-catenin,and decreased expression of GSK-3β.All differences were statistically significant(P<0.05).Pathological observations revealed that the model group had blurred and abnormal myocardial tissue structure,disordered cardiomyocyte arrangement with hypertrophy,pyknosis,and necrosis,thickened and broken myocardial fibers,tissue swelling,extensive blue collagen proliferation in the myocardial interstitium,and significant myocardial fibrosis.Compared with the model group,the saikosaponin D treatment groups showed significant improvement in pathological damage.Compared with the high-dose saikosaponin D group,the high-dose saikosaponin D+LiCl group exhibited aggravated pathological damage in myocardial tissue.Conclusion:Saikosa-ponin D can improve myocardial fibrosis in CHF rats,and its mechanism may be related to the inhibition of the Wnt/β-catenin signaling pathway.关键词
慢性心力衰竭/柴胡皂苷D/Wnt/β-catenin信号通路/心肌纤维化/大鼠Key words
chronic heart failure(CHF)/saikosaponin D/Wnt/β-catenin signaling pathway/myocardial fibrosis/rats分类
医药卫生引用本文复制引用
王晓宇,张喜召..柴胡皂苷D调控Wnt/β-catenin信号通路改善慢性心力衰竭大鼠心肌纤维化[J].河南中医,2025,45(10):1551-1558,8.基金项目
河南省医学科技攻关计划项目(LHGJ20200692) （LHGJ20200692）
