Geng Deng-feng, Wu Wei, Jin Dong-mei, Wang Jing-feng, Wu Yi-mei
Department of Cardiology, The Second Affiliated Hospital, SUN Yat-sen University, West Yanjiang Road, Guangzhou, 510120, China.
Int J Cardiol. 2006 Oct 26;113(1):86-91. doi: 10.1016/j.ijcard.2006.03.060. Epub 2006 Aug 7.
Recent studies have demonstrated that PPARgamma ligands have anti-inflammatory effect which is involved in ventricular remodeling. So we hypothesized that PPARgamma ligand may have beneficial effects on post-infarct ventricular remodeling.
Experimental myocardial infarction (MI) was induced in SD rats by ligation of the left coronary artery. Twenty-four hours after surgery, survival rats were randomly divided into MI group and Rosiglitazone (MI+Ros) group which would take rosiglitazone 3 mg/kg day for 8 weeks. After 8 weeks treatment, left ventricular hemodynamics were measured and organs were weighed. Myocardial collagen analysis was determined in Van Gieson staining by quantitative morphometry. Myocardial angiotensin II and aldosterone were detected by radioimmunoassay. Myocardial AT1 and AT2 mRNA expression were determined by RT-PCR.
Only 1 rat in MI group died of anesthesia at the 8th week. Rosiglitazone treatment could improve left ventricular +/-dp/dt(max), collagen volume fraction and perivascular circumferential area; reduce lung/body mass ratio and liver/body mass ratio; inhibit myocardial angiotensin II and aldosterone; and had no significant effects on myocardial AT1 and AT2 mRNA. Plasma insulin and blood glucose were comparable between two groups.
PPARgamma ligand has neutral effect on mortality and beneficial effect on post-infarct ventricular remodeling, partly by suppressing myocardial angiotensin II and aldosterone, irrespective of plasma insulin and blood glucose level.
近期研究表明,过氧化物酶体增殖物激活受体γ(PPARγ)配体具有抗炎作用,且参与心室重构。因此,我们推测PPARγ配体可能对心肌梗死后心室重构具有有益作用。
通过结扎左冠状动脉在SD大鼠中诱导实验性心肌梗死(MI)。手术后24小时,存活的大鼠被随机分为MI组和罗格列酮组(MI+Ros),罗格列酮组大鼠每天给予3mg/kg罗格列酮,持续8周。8周治疗后,测量左心室血流动力学并对器官进行称重。通过定量形态学在Van Gieson染色中测定心肌胶原分析。通过放射免疫测定法检测心肌血管紧张素II和醛固酮。通过逆转录聚合酶链反应(RT-PCR)测定心肌AT1和AT2 mRNA表达。
MI组仅1只大鼠在第8周死于麻醉。罗格列酮治疗可改善左心室+/-dp/dt(max)、胶原容积分数和血管周围圆周面积;降低肺/体重比和肝/体重比;抑制心肌血管紧张素II和醛固酮;并且对心肌AT1和AT2 mRNA无显著影响。两组之间的血浆胰岛素和血糖水平相当。
PPARγ配体对死亡率具有中性作用,对心肌梗死后心室重构具有有益作用,部分是通过抑制心肌血管紧张素II和醛固酮,与血浆胰岛素和血糖水平无关。