雷米普利对大鼠高血压并发左心室心肌肥厚伴心肌舒张功能不全和血管纤维化的作用

Effects of ramipril on diastolic dysfunction and cardiac fibrosis in hypertensive rats accompanied by left ventricular hypertrophy

目的探讨雷米普利对舒张性心力衰竭的治疗作用。方法45只雄性Spargue-Dawley大鼠随机分为假手术组、心肌肥厚模型组和雷米普利治疗组。采用腹主动脉缩窄手术制备心肌肥厚模型,造模12周后ig给予雷米普利1mg·kg-1,每天1次,连续12周。颈动脉插管法测定大鼠左心室舒张末压(LVEDP)、左心室收缩压(LVSP)和左心室压变化速率最大值(±dp/dtmax);测定心脏重量指数和左心室重量指数(LVMI);Van Gieson染色法测定心肌间质和心肌血管纤维化程度;实时PCR法测定胶原Ⅰ型和胶原Ⅲ型mRNA表达。结果与假手术组相比,模型组大鼠LVEDP和LVSP分别升高了103.9%和37.7%;LVMI、心肌间质和血管纤维化分别增加了35.5%,306.3%和104.1%;胶原Ⅰ型和胶原Ⅲ型mRNA表达分别上调2.1倍和4.4倍。与模型组大鼠比较,雷米普利组大鼠LVEDP,LVSP和LVMI分别降低了62.5%,27.4%和18.6%;大鼠心肌间质和心肌血管的纤维化分别降低了44.9%和55.6%;心肌组织胶原Ⅰ型和胶原Ⅲ型mRNA表达分别降低了44.8%和67.0%。结论雷米普利能改善高血压并发左心室心肌肥厚伴心肌舒张功能不全大鼠的心肌舒张功能,可能与其延缓心肌纤维化的病理进程有关,提示雷米普利对舒张性心力衰竭可能有一定的治疗作用。

OBJECTIVE To investigate therapeutic action of ramipril on diastolic heart failure. METHODS Forty five Spargue-Dawley rats were randomly divided into sham, model and ramipril groups. Left ventricular hypertrophy was induced by abdominal aorta banding for 12 weeks. Then the rats were treated with carboxymethylcellulose or ramipril 1.0 mg·kg-1 for 12 weeks, respectively. Systolic and diastolic functions were obtained by hemodynamic studies in vivo. The left ventricle mass index (LVMI) and heart weight index were calculated by morphometric analysis. The cardiac fibrosis was detected by Van Gieson staining.Gene expressions of collagenⅠ and collagenⅢ were determined by Real-time PCR, respectively. RESULTS Compared with sham-operated rats, the left ventricle end diastolic pressure (LVEDP) and left ventricle systolic pressure (LVSP) of rats in model group increased by 103.9% and 37.7%, respectively; LVMI, cardiac interstitial and vascular fibrosis was significantly increased by 35.5%, 306.3% and 104.1%;gene expression of collagenⅠ and collagenⅢ increased 3.1- and 5.4-fold in model rats, respectively. Ramipril decreased the elevated LVEDP, LVSP and LVMI by 62.5%, 27.4% and 18.6%, respectively; ramipril decreased cardiac interstitial and vascular fibrosis as well as collagenⅠ and collagenⅢ mRNA expression by 44.9%, 55.6%, 44.8% and 67.0%, respectively. CONCLUSION Ramipril improves diastolic function in rats with pressure overload-induced cardiac hypertrophy with diastolic dysfunction partly by inhibiting cardiac fibrosis development.