本文選題：芪藶強心 + 雌激素缺失��； 參考：《南京醫(yī)科大學》2017年博士論文

【摘要】：目的:急性心肌梗死(心梗)因其高發(fā)病率及高致殘率,已成為當今世界面臨的重大疾病之一。絕經(jīng)期后婦女因缺乏雌激素的保護,心梗的發(fā)病率較絕經(jīng)期前顯著上升且預后較絕經(jīng)期前婦女或同齡男性更差。本課題組前期的多中心隨機對照雙盲研究證實芪藶強心膠囊對臨床心衰病人的治療效果確切。本課題以雙側卵巢切除小鼠模擬臨床絕經(jīng)期后的婦女,旨在探究中藥芪藶強心對雌激素缺失小鼠心梗后心室重構和慢性心力衰竭的保護作用及其分子機制。方法:本課題實驗對象為8周齡大C57BL/6雌性小鼠,首先進行雙側卵巢切除手術,卵巢切除術后7天,采用結扎冠狀動脈前降支的方法建立心梗模型,心梗后第一天起口飼芪藶強心溶液0.5g/kg/d,連續(xù)治療21天。21天后到達實驗終點,用小動物心臟超聲成像系統(tǒng)檢測各組小鼠心功能,用馬松染色評估心肌纖維化,并通過實時定量聚合酶鏈式反應(polymerase chain reaction,PCR)檢測Collagen Ⅰ,Collagen Ⅲ和α-SMA來評估心臟膠原沉積,用凋亡染色評估心肌凋亡,用蛋白免疫印跡檢測相關信號通路;在明確芪藶強心上調(diào)過氧化物酶體增殖物激活受體 γ(peroxisome proliferator activated receptor γ,PPARγ)后,通過在口飼芪藶強心的同時腹腔注射PPARγ激動劑羅格列酮或PPARγ抑制劑T0070907的方法,驗證過表達或抑制PPARγ是否使芪藶強心對雌激素缺失小鼠心梗后的治療作用進一步增強或減弱,從而明確PPARγ是否為芪藶強心減輕雌激素缺失小鼠心梗后心室重構和慢性心力衰竭所必須;最后用PCR檢測了心臟能量代謝相關的基因表達水平,觀察卵巢切除,心梗及芪藶強心治療對心肌能量代謝的影響。結果:結果表明雌激素缺失小鼠心梗后21天心臟射血分數(shù)(ejection fraction,EF)及短軸縮短率(shortening fraction,FS)較假手術組明顯下降,心肌纖維化及心肌凋亡明顯增加,PPARγ表達下降;芪藶強心治療組較安慰劑治療組相比,芪藶強心可提高心功能(EF及FS),減輕心肌纖維化及心肌凋亡,并上調(diào)PPARγ水平;用T0070907抑制PPARγ后,芪藶強心保護雌激素缺失小鼠心梗后心功能及心室重構的作用被抑制,而羅格列酮并不能進一步增強芪藶強心的心臟保護功能;之后的實驗進一步證明芪藶強心可促進心梗小鼠慢性重構期的能量代謝相關基因(Cd36,Fatp,Pdk4,Acadm,Acad1,Acadv1,Cpt1a,Cpt1b 和 Cpt2)表達上調(diào)。結論:芪藶強心可通過上調(diào)PPARγ減輕雌激素缺失小鼠心梗后心室重構及慢性心力衰竭,提示我們芪藶強心可能成為臨床治療上絕經(jīng)后婦女慢性缺血性心臟病的有效藥物。
[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，

本文編號：2071592