Sheu Jiunn-Jye, Chang Li-Teh, Chiang Chiang-Hua, Sun Cheuk-Kwan, Chang Nyuk-Kong, Youssef Ali A, Wu Chiung-Jen, Lee Fan-Yen, Yip Hon-Kan
Department of Cardiovascular Surgery, Chang Gung Memorial Hospital, Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung Hsien, Taiwan, ROC.
Int Heart J. 2007 Mar;48(2):233-45. doi: 10.1536/ihj.48.233.
The integrity of myocardial structures plays a crucial role in signal transductions and cardiac function. The aim of this study was to test the hypothesis that diabetes mellitus (DM) exerts adverse effects on the integrity of gap junctions (GJs) and induces cellular apoptosis in rat cardiomyocytes that can be abolished by simvastatin or losartan therapy. An experimental model of DM (induced by streptozocin 60 mg/kg body weight) in adult male rats (n = 24) was utilized to investigate the integrity of GJs containing connexin43 (Cx43) and the incidence of cellular apoptosis in the left ventricular myocardium. These rats were divided into 3 groups; group I (insulin therapy only), group II (insulin plus simvastatin 20 mg/kg/day), and group III (insulin plus losartan 20 mg/kg/day). Diabetic rats and 8 healthy rats (group IV) were sacrificed at 3 weeks following DM induction for immunofluorescence analysis. The experimental results demonstrated that the number of intact Cx43 GJs and the integrated area (mum(2)) constituted by clusters of Cx43 spots were significantly higher in groups II and IV than in group III, and in groups II-IV than in group I (all P values < 0.05). Additionally, the number of apoptotic bodies was remarkably higher in group I than in groups II-IV, and notably higher in groups II-III than in group IV (all P values < 0.05). Simvastatin is more effective than losartan at inhibiting the effects of DM on the integrity of myocardial ultrastructures. Both drugs effectively prevent cellular apoptosis in diabetic rat heart.
心肌结构的完整性在信号转导和心脏功能中起着至关重要的作用。本研究的目的是验证以下假设：糖尿病（DM）对缝隙连接（GJ）的完整性产生不利影响，并诱导大鼠心肌细胞发生细胞凋亡，而辛伐他汀或氯沙坦治疗可消除这种影响。利用成年雄性大鼠（n = 24）的DM实验模型（通过链脲佐菌素60 mg/kg体重诱导）来研究含连接蛋白43（Cx43）的GJ的完整性以及左心室心肌细胞凋亡的发生率。这些大鼠被分为3组；第一组（仅胰岛素治疗），第二组（胰岛素加辛伐他汀20 mg/kg/天），第三组（胰岛素加氯沙坦20 mg/kg/天）。在DM诱导后3周处死糖尿病大鼠和8只健康大鼠（第四组）进行免疫荧光分析。实验结果表明，第二组和第四组中完整的Cx43 GJ数量以及由Cx43斑点簇构成的整合面积（μm²）显著高于第三组，第二至四组高于第一组（所有P值<0.05）。此外，第一组中的凋亡小体数量显著高于第二至四组，第二至三组显著高于第四组（所有P值<0.05）。在抑制DM对心肌超微结构完整性的影响方面，辛伐他汀比氯沙坦更有效。两种药物均能有效预防糖尿病大鼠心脏的细胞凋亡。
