| 本文已被：浏览 3088次 下载 2986次 |
码上扫一扫！ |
| Urocortin抑制心肌缺血再灌注诱导的自噬 |
| 张冠鑫1,韩林1*,郭志福1,王崇1,任安经2,钟铿1,李鑫1,袁扬1,徐志云1 |
|
|
(1. 第二军医大学长海医院胸心外科,上海 200433
2. 第二军医大学基础部生理学教研室,上海 200433
*通信作者) |
|
| 摘要: |
| 目的 研究urocortin(UCN)对缺血再灌注诱导的心肌细胞自噬的影响,探讨UCN的心肌保护机制。方法 构建大鼠在体心脏缺血再灌注损伤和离体新生大鼠心肌细胞的缺氧复氧模型,进行缺血/缺氧1 h再灌注/复氧2 h的损伤,在缺血/缺氧前1 h给予UCN预处理；在再灌注/复氧2 h后观察UCN对缺血再灌注/缺氧复氧诱导的心肌损伤、细胞自噬和自噬相关基因表达的影响。结果 UCN预处理可以显著降低缺血再灌注损伤导致的心肌损害,使梗死面积降低,血清肌酸激酶(CK)、乳酸脱氢酶(LDH)降低；增加缺氧复氧离体心肌细胞活力、减少培养上清的LDH水平。与上述心肌保护作用相伴随的是UCN预处理还能抑制缺氧复氧导致的心肌细胞自噬,使LC3BⅡ/LC3BⅠ的比值显著降低,并且抑制自噬相关基因Beclin1、Bnip3的mRNA表达。结论 UCN可以抑制缺血再灌注诱导的心肌细胞自噬,可能在抗缺血再灌注损伤中起重要作用。 |
| 关键词: urocortin 心肌缺血 心肌再灌注损伤 心肌细胞 自噬 |
| DOI：10.3724/SP.J.1008.2013.0011 |
| 投稿时间：2012-12-23修订日期：2013-01-05 |
| 基金项目:国家卫生部公益基金(200802096). |
|
| Urocortin inhibits myocardium ischemia/reperfusion-induced autophagy |
| ZHANG Guan-xin1,HAN Lin1*,GUO Zhi-fu1,WANG Chong1,REN An-jing2,ZHONG Keng1,LI Xin1,YUAN Yang1,XU Zhi-yun1 |
(1. Department of Cardiothoracic Surgery, Changhai Hospital, Second Military Medical University, Shanghai 200433, China
2. Department of Physiology, College of Basic Medical Sciences, Second Military Medical University, Shanghai 200433, China
*Corresponding author.) |
| Abstract: |
| Objective To study the regulatory effect of urocortin (UCN) on ischemia/reperfusion (I/R)-induced myocardial autophagy, so as to explore the myocardial protection mechanism of UCN. Methods Cardiac I/R model was established with rats and hypoxia/reoxygenation(H/R) model was also established with neonatal rat cardiomyocytes. The injury was created by ischemic/hypoxia for 1 h plus reperfusion/reoxygenation for 2 h, and UCN pretreatment was given 1 h before ischemia/hypoxia. The I/R or H/R-induced myocardial injury, myocardial autophagy and autophagy-related gene expression were observed 2 h after reperfusion/reoxygenation. Results UCN pretreatment greatly reduced I/R-induced myocardial damage by decreasing the infarct size, serum creatine kinase (CK) and lactate dehydrogenase (LDH) concentration, increasing the vitality of H/R cardiomyocytes in vitro, and reducing LDH level in the culture supernatant. Moreover, UCN pretreatment also inhibited H/R-induced myocardial autophagy by reducing the ratio of LC3BⅡ/LC3BⅠ and inhibiting expression of autophagy-related genes (Beclin1 and Bnip3). Conclusion UCN can inhibit I/R-induced myocardial autophagy, which may play an important role in the protection against I/R injury. |
| Key words: urocortin myocardial ischemia myocardial reperfusion injury cardiac myocytes autophagy |
