摘要
目的:探讨灯盏花素对急性心肌梗死(AMI)大鼠心室重构的影响及其机制。方法:采用左侧冠状动脉结扎法建立AMI模型,随机分为模型组、灯盏花素Ⅰ组、灯盏花素Ⅱ组、TGF-β1激活剂组和阳性对照组,另设假手术组,分别灌胃给予生理盐水、50、200 mg/kg灯盏花素、10 mg/kg TGF-β1激活剂+200 mg/kg灯盏花素、100 mg/kg阿司匹林肠溶片、生理盐水。超声和生理检测系统检测大鼠心脏功能指标变化。HE染色实验观察大鼠心肌组织病理学变化。Masson染色法检测鼠心肌组织胶原沉淀情况。Western blot检测TGF-β1、Smads2/3、p-Smads2/3和Smads7蛋白表达。结果:与对照组相比,模型组大鼠左心室EDd和ESd值、心肌组织TGF-β1、p-Smads2和p-Smads3蛋白表达显著升高(P<0.05),EF和FS值、+dp/dtmax和-dp/dtmax值、Smads7蛋白表达显著降低(P<0.05),心肌细胞排列紊乱,细胞间隙显著扩大,间质胶原明显沉积;与模型组相比,灯盏花素I组、灯盏花素Ⅰ组和阳性对照组上述各指标均显著改善,大鼠心肌细胞排列趋于规则,细胞间隙明显缩小,胶原密度明显降低;TGF-β1激活剂组大鼠左心室EDd和ESd值、心肌组织中TGF-β1、p-Smads2和p-Smads3蛋白表达显著升高(P<0.05),EF和FS值、+dp/dtmax和-dp/dtmax值、Smads7蛋白表达显著降低(P<0.05),心肌细胞排列不规则,细胞间隙扩大,胶原沉积增多。结论:灯盏花素可通过抑制TGF-β1/Smads信号通路减轻心室重构,治疗AMI。
Objective:To explore effect of breviscapine on ventricular remodeling in rats with acute myocardial infarction(AMI)and its mechanism.Methods:AMI model was established by ligation of left coronary artery,and divided into model group,breviscapineⅠgroup,breviscapineⅡgroup,TGF-β1 activator group,positive control group,and set up sham group,then sequentially treated with normal saline,50,200 mg/kg breviscapine,10 mg/kg TGF-β1 activator+200 mg/kg breviscapine,100 mg/kg aspirin enteric coated tablets,normal saline by gavage.Changes of cardiac function indexes were detected by ultrasound and physiological detection system.HE staining was used to observe pathological changes of myocardial tissue.Masson staining was used to detect collagen deposition in myocardial tissue.Western blot analysis was used to detect transforming growth factor-β1(TGF-β1),Smads2/3,pSmads2,p-Smads3 and Smads7 protein expressions.Results:Compared with control group,values of EDd and ESd in left ventricle and protein expressions of TGF-β1,p-Smads2 and p-Smads3 in myocardial tissue in model group were significantly increased(P<0.05),values of EF and FS,values of+dp/dtmaxand-dp/dtmax,protein expressions of Smads7 were significantly decreased(P<0.05),arrangement of myocardial cells was disordered,intercellular space was enlarged significantly,and interstitial collagen was obviously deposited.Compared with model group,above indexes in breviscapineⅠgroup,breviscapineⅡgroup and positive control group were significantly improved,arrangement of myocardial cells in rats tended to be regular,intercellular space was significantly reduced,collagen density was significantly decreased,values of EDd and ESd in left ventricle and protein expressions of TGF-β1,pSmads2 and p-Smads3 in myocardial tissue in TGF-β1 activator group were significantly increased(P<0.05),values of EF and FS,values of+dp/dtmaxand-dp/dtmax,protein expressions of Smads7 were significantly decreased(P<0.05),irregularity of myocardial cells became worse,space between cells became larger,and collagen deposition was increased.Conclusion:Breviscapine can reduce ventricular remodeling and achieve therapeutic effect of AMI by inhibiting TGF-β1/Smads signaling pathway.
作者
赵博
彭建军(指导)
李广平
任利辉
ZHAO Bo;PENG Jian⁃Jun;LI Guang⁃Ping;REN Li⁃Hui(Department of Cardiology,Beijing Shijitan Hospital,Affiliated to Capital Medical University,Beijing 100038,China)
出处
《中国免疫学杂志》
CAS
CSCD
北大核心
2021年第4期410-414,共5页
Chinese Journal of Immunology
基金
北京市自然科学基金(7162089)