金雀异黄酮通过Toll样受体4信号通路改善急性心肌梗死大鼠左心室功能的研究  

Improvement of left ventricular function in rats with acute myocardial infarction through Toll-like receptor 4 signaling pathway by genistein

作　　者：姚飞 郭云亢 张丽娜[2] Yao Fei;Guo Yunkang;Zhang Lina(Department of Ultrasound,Handan Iron and Steel Hospital,Handan 056001,China;Third Department of Cardiology,Handan Central Hospital,Handan 056000,China)

机构地区：[1]邯郸邯钢医院超声科,邯郸056001 [2]河北省邯郸市中心医院心内三科,056000

出　　处：《心脑血管病防治》2024年第3期5-10,63,F0003,共8页CARDIO-CEREBROVASCULAR DISEASE PREVENTION AND TREATMENT

基　　金：河北省医学科学研究课题(20210854)。

摘　　要：目的基于Toll样受体4(TLR4)信号通路探讨金雀异黄酮(GEN)对急性心肌梗死(AMI)大鼠左心室功能的影响及潜在机制。方法100只雄性SD大鼠随机分为假手术组、模型组、GEN(GEN,40 mg/kg)组、GEN+TAK242(TLR4抑制剂,10 mg/kg)组和GEN+LPS(TLR4激动剂,5 mg/kg)组,每组20只。采用结扎冠状动脉左前降支的方法构建AMI大鼠模型,经1次/d给药治疗4周后,通过心脏超声检测大鼠左心室功能;酶联免疫吸附实验(ELISA)法检测血清血管紧张素Ⅱ(AngⅡ)、基质裂解素2(ST2)、脑利钠肽(BNP)水平;计算左心室质量指数(LVMI);苏木精-伊红(HE)染色法观察左心室心肌组织病理学改变;马森(Masson)染色法观察左心室心肌组织纤维化状况并计算胶原容积分数(CVF);ELISA法检测左心室心肌组织肿瘤坏死因子-α(TNF-α)、白细胞介素(IL)-1β、IL-6水平;蛋白免疫印迹法检测TLR4、核因子-κB p65(NF-κB p65)、磷酸化NF-κB p65(p-NF-κB p65)、转化生长因子-β1(TGF-β1)、Ⅰ型胶原(Col-Ⅰ)、Col-Ⅲ、α-平滑肌肌动蛋白(α-SMA)蛋白表达。结果与模型组比较,GEN组左心室功能改善,左心室收缩末期内径(LVIDs)和左心室舒张末期内径(LVIDd)降低,左心室短轴缩短率(LVFS)和左心室射血分数(LVEF)升高;血清AngⅡ、ST2、BNP水平和LVMI降低;左心室心肌组织病理性改变和纤维化状况均改善,CVF降低;心肌组织TNF-α、IL-1β、IL-6水平降低;TLR4、TGF-β1、Col-Ⅰ、Col-Ⅲ、α-SMA表达量和p-NF-κB p65/NF-κB p65比值降低,差异均有统计学意义(P<0.05)。TAK242能够增强GEN对AMI大鼠上述指标的调控作用;LPS则能够阻断GEN对AMI大鼠各指标的调控作用。结论GEN具有抑制AMI大鼠心室重构,改善左心室功能的作用,其机制可能与抑制TLR4信号通路,减轻炎症反应,减少细胞外基质生成有关。Objective To explore the effect and potential mechanism of genistein(GEN)on left ventricular function in rats with acute myocardial infarction(AMI)based on Toll-like receptor 4(TLR4)signaling pathway.Methods One hundred male SD rats were randomly divided into sham operation group,model group,GEN(40 mg/kg)group,GEN+TAK242(TLR4 inhibitor,10 mg/kg)group,and GEN+LPS(TLR4 activator,5 mg/kg)group,with 20 rats in each group.The AMI rat model was established by ligation of the left anterior descending coronary artery.After intragastric administration once a day for 4 weeks,left ventricular function was detected by cardiac ultrasound.The levels of angiotensinⅡ(AngⅡ),stromal lysin 2(ST2),and brain natriuretic peptide(BNP)in serum were determined by enzyme linked immunosorbent assay(ELISA).Left ventricular mass index(LVMI)was calculated,and histopathological changes in left ventricular myocardial tissue were observed by hematoxylin-eosin(HE)staining.Fibrosis in left ventricular myocardial tissue was observed by Masson staining,and the collagen volume fraction(CVF)was calculated.The levels of tumor necrosis factor(TNF)-α,interleukin-1β(IL-1β),IL-6 in left ventricular myocardial tissue were determined by ELISA.Protein expression of TLR4,nuclear factor-κB p65(NF-κB p65),p-NF-κB p65,transforming growth factor-β1(TGF-β1),Collagen(Col)-Ⅰ,Col-Ⅲ,α-smooth muscle actin(α-SMA)was detected by Western blot.Results Compared with the model group,the heart function in GEN group was significantly improved,left ventricular internal diameter at end-systolic(LVIDs)and left ventricular internal diameter at end-diastolic(LVIDd)reduced,left ventricular fractional shortening(LVFS)and left ventricular ejection fraction(LVEF)increased;serum levels of AngⅡ,ST2,BNP,and LVMI were decreased;pathological changes and fibrosis of left ventricular myocardial tissue were significantly improved,CVF was decreased;the levels of TNF-α,IL-1β,IL-6 in myocardial tissue were decreased;the expression of TLR4,TGF-β1,Col-Ⅰ,Col-Ⅲ,α-SMA and th

关 键 词：急性心肌梗死 金雀异黄酮 TLR4信号通路 炎症 细胞外基质 

分 类 号：R285.5[医药卫生—中药学]