Xing Wenjuan, Yan Wenjun, Fu Feng, Jin Yulan, Ji Lele, Liu Wenchong, Wang Li, Lv Anlin, Duan Yunyan, Zhang Jun, Zhang Haifeng, Gao Feng
Department of Physiology, Xijing Hospital, Fourth Military Medical University, 710032, Xi'an, China.
Apoptosis. 2009 Sep;14(9):1050-60. doi: 10.1007/s10495-009-0378-y.
Insulin has been shown to possess significant anti-apoptotic effect in myocardial ischemia/reperfusion (MI/R). However, the contribution by this protection of insulin to the prolonged cardiac function in rats subjected to ischemia remains unclear. The present study attempted to test whether early insulin treatment influences adverse prolonged post-ischemic cardiac structural and functional changes. Adult male rats were subjected to left anterior descending coronary artery occlusion and were randomized to receive one of the following treatments: saline (4 ml/kg/h i.v. injection beginning 10 min before the ischemia and continuing for 2 h), insulin (60 U/l, i.v. injection following the same routine, and hypodermic injection of insulin (0.5 U/ml, 1 ml/kg/d) for 3 days after the ischemia surgery) or insulin plus wortmannin (15 mug/kg i.v. injection 15 min before each insulin administration). Treatment with insulin significantly reduced infarct size, decreased plasma creatine kinase and lactate dehydrogenase activities, decreased apoptosis index and caspase-3 activity (all P < 0.01 vs. saline), and improved cardiac function 24 h after ischemia. Importantly, at the end of 4 weeks after the ischemia surgery, MI rats receiving insulin treatment showed smaller left ventricle (LV) cavity and thicker systolic interventricular septum, and increased cardiac ejection fraction and LV fractional shortening (all P < 0.05 vs. saline). Inhibition of insulin signaling with wortmannin not only blocked insulin's anti-apoptotic effect, but also almost completely abolished effects of insulin on cardiac structure and function. These data indicate that inhibition of apoptosis by early insulin treatment alleviates chronic adverse changes in post-ischemic cardiac structure and function.
胰岛素已被证明在心肌缺血/再灌注（MI/R）中具有显著的抗凋亡作用。然而，胰岛素的这种保护作用对缺血大鼠心脏功能延长的贡献仍不清楚。本研究试图测试早期胰岛素治疗是否会影响缺血后不良的心脏结构和功能长期变化。成年雄性大鼠接受左冠状动脉前降支闭塞，并随机接受以下治疗之一：生理盐水（在缺血前10分钟开始静脉注射4 ml/kg/h，持续2小时）、胰岛素（60 U/l，按照相同程序静脉注射，并在缺血手术后皮下注射胰岛素（0.5 U/ml，1 ml/kg/d），持续3天）或胰岛素加渥曼青霉素（在每次胰岛素给药前15分钟静脉注射15 μg/kg）。胰岛素治疗显著减小了梗死面积，降低了血浆肌酸激酶和乳酸脱氢酶活性，降低了凋亡指数和半胱天冬酶-3活性（与生理盐水组相比，所有P < 0.01），并改善了缺血后24小时的心脏功能。重要的是，在缺血手术后4周结束时，接受胰岛素治疗的MI大鼠左心室（LV）腔较小，收缩期室间隔较厚，心脏射血分数和LV缩短分数增加（与生理盐水组相比，所有P < 0.05）。渥曼青霉素抑制胰岛素信号传导不仅阻断了胰岛素的抗凋亡作用，而且几乎完全消除了胰岛素对心脏结构和功能的影响。这些数据表明，早期胰岛素治疗抑制凋亡可减轻缺血后心脏结构和功能的慢性不良变化。
