Wu Yan-Na, Chen Yan, Zhang Zhe, Dong Ya-Li, Yu Xue-Kuan, Jiao Jian-Jie, Kang Yi, Gao Wei-Zhen, Lou Jian-Shi, Liu Yan-Xia
Department of Pharmacology, Tianjin Medical University, Tianjin 300070, China.
Zhongguo Ying Yong Sheng Li Xue Za Zhi. 2009 Nov;25(4):485-9.
To investigate the effects of ramipril on myocardial ischemia/reperfusion injury in diabetic rats, and to explore its mechanism according to the observation on myocardial ultrastructure.
Streptozotocin induced diabetic rats were divided randomly into three groups (n = 16): ischemia/reperfusion (I/R), ischemic preconditioning (IPC) and ramipril (RAM) group. Rats in RAM group were administered by RAM(1 mg x kg(-1) x d(-1)) orally for 4 weeks, the others were administered by normal saline. Then all rats were subjected to myocardial ischemia/ reperfusion injury. Rats in IPC group were preconditioned before ischemia. The ECG and the infarct size were examined. The changes of myocardial morphology were examined by light and electron microscopes.
Compared with I/R group, the elevation of ST segment and the incidence of ventricular tachycardia and ventricular fibrillation during ischemia were significantly decreased, the infarct size at the end of reperfusion was remarkably reduced, the myocardial morphology were significantly improved, special structure of myofilaments and mitochondria remained clearly, blood vessels were unobstructed, injury of endothelium were decreased in PC and RAM groups.
Ramipril administered for 4 weeks induces myocardial protection in diabetic rats, which is similar to that of IPC. The mechanism may be involved in protection of cardiocytes and mitochondria, and improvement of endothelial function.
研究雷米普利对糖尿病大鼠心肌缺血/再灌注损伤的影响,并通过观察心肌超微结构探讨其作用机制。
将链脲佐菌素诱导的糖尿病大鼠随机分为三组(n = 16):缺血/再灌注组(I/R)、缺血预处理组(IPC)和雷米普利组(RAM)。RAM组大鼠口服雷米普利(1 mg·kg⁻¹·d⁻¹)4周,其余组大鼠给予生理盐水。然后所有大鼠均进行心肌缺血/再灌注损伤实验。IPC组大鼠在缺血前进行预处理。检测心电图和梗死面积。通过光镜和电镜观察心肌形态学变化。
与I/R组相比,PC组和RAM组缺血期间ST段抬高及室性心动过速和室颤发生率明显降低,再灌注结束时梗死面积显著减小,心肌形态明显改善,肌丝和线粒体的特殊结构保持清晰,血管通畅,内皮损伤减轻。
雷米普利给药4周可诱导糖尿病大鼠心肌保护,其作用与IPC相似。机制可能与保护心肌细胞和线粒体以及改善内皮功能有关。