芪苈强心减轻雌激素缺失小鼠心肌梗死后心室重构的作用及其机制研究

发布时间：2018-06-26 22:15

  本文选题：芪苈强心 + 雌激素缺失　； 参考：《南京医科大学》2017年博士论文

【摘要】：目的:急性心肌梗死(心梗)因其高发病率及高致残率,已成为当今世界面临的重大疾病之一。绝经期后妇女因缺乏雌激素的保护,心梗的发病率较绝经期前显著上升且预后较绝经期前妇女或同龄男性更差。本课题组前期的多中心随机对照双盲研究证实芪苈强心胶囊对临床心衰病人的治疗效果确切。本课题以双侧卵巢切除小鼠模拟临床绝经期后的妇女,旨在探究中药芪苈强心对雌激素缺失小鼠心梗后心室重构和慢性心力衰竭的保护作用及其分子机制。方法:本课题实验对象为8周龄大C57BL/6雌性小鼠,首先进行双侧卵巢切除手术,卵巢切除术后7天,采用结扎冠状动脉前降支的方法建立心梗模型,心梗后第一天起口饲芪苈强心溶液0.5g/kg/d,连续治疗21天。21天后到达实验终点,用小动物心脏超声成像系统检测各组小鼠心功能,用马松染色评估心肌纤维化,并通过实时定量聚合酶链式反应(polymerase chain reaction,PCR)检测Collagen Ⅰ,Collagen Ⅲ和α-SMA来评估心脏胶原沉积,用凋亡染色评估心肌凋亡,用蛋白免疫印迹检测相关信号通路;在明确芪苈强心上调过氧化物酶体增殖物激活受体 γ(peroxisome proliferator activated receptor γ,PPARγ)后,通过在口饲芪苈强心的同时腹腔注射PPARγ激动剂罗格列酮或PPARγ抑制剂T0070907的方法,验证过表达或抑制PPARγ是否使芪苈强心对雌激素缺失小鼠心梗后的治疗作用进一步增强或减弱,从而明确PPARγ是否为芪苈强心减轻雌激素缺失小鼠心梗后心室重构和慢性心力衰竭所必须;最后用PCR检测了心脏能量代谢相关的基因表达水平,观察卵巢切除,心梗及芪苈强心治疗对心肌能量代谢的影响。结果:结果表明雌激素缺失小鼠心梗后21天心脏射血分数(ejection fraction,EF)及短轴缩短率(shortening fraction,FS)较假手术组明显下降,心肌纤维化及心肌凋亡明显增加,PPARγ表达下降;芪苈强心治疗组较安慰剂治疗组相比,芪苈强心可提高心功能(EF及FS),减轻心肌纤维化及心肌凋亡,并上调PPARγ水平;用T0070907抑制PPARγ后,芪苈强心保护雌激素缺失小鼠心梗后心功能及心室重构的作用被抑制,而罗格列酮并不能进一步增强芪苈强心的心脏保护功能;之后的实验进一步证明芪苈强心可促进心梗小鼠慢性重构期的能量代谢相关基因(Cd36,Fatp,Pdk4,Acadm,Acad1,Acadv1,Cpt1a,Cpt1b 和 Cpt2)表达上调。结论:芪苈强心可通过上调PPARγ减轻雌激素缺失小鼠心梗后心室重构及慢性心力衰竭,提示我们芪苈强心可能成为临床治疗上绝经后妇女慢性缺血性心脏病的有效药物。
[Abstract]:Objective: acute myocardial infarction (AMI) has become one of the most important diseases in the world because of its high morbidity and high disability rate. The incidence of MI in postmenopausal women was significantly higher than that in premenopausal women and the prognosis was worse than that of premenopausal women or men of the same age due to the lack of estrogen protection. A multicenter, randomized, double-blind study by our research group confirmed that Qiliqiangxin capsule was effective in the treatment of clinical heart failure patients. In this study, bilateral ovariectomized mice were used to simulate postmenopausal women in order to explore the protective effect and molecular mechanism of Qiliqiangxin on ventricular remodeling and chronic heart failure after estrogen deficiency in mice. Methods: the female C57BL / 6 mice aged 8 weeks were treated with bilateral ovariectomies. The myocardial infarction model was established by ligating the anterior descending branch of coronary artery 7 days after ovariectomy. On the first day after myocardial infarction, Qiliqiangxin solution was orally fed with Qiliqiangxin solution 0.5 g / kg / d. After continuous treatment for 21 days and 21 days, it reached the end of the experiment. The cardiac function of each group was measured by small animal heart ultrasound imaging system, and myocardial fibrosis was evaluated by Ma Song staining. Collagen 鈪，

本文编号：2071592