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白黎芦醇减轻Ⅱ型糖尿病小鼠心肌缺血/再灌注损伤的作用(PDF)

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2012年第3期
页码:
292-297
栏目:
基础研究
出版日期:
2012-06-25

文章信息/Info

Title:
Role of resveratrol in attenuating myocardial ischemia/reperfusion injury in type II diabetic mice
作者:
杨 强; 王海昌; 高 超; 冯世栋; 孙 璐; 刘 毅; 陶 凌
(第四军医大学西京医院心血管内科，陕西 西安 710032)
Author(s):
YANG Qiang;  WANG Hai-chang;  GAO Chao;  FENG Shi-dong;  SUN Lu;  LIU Yi;  TAO Ling
(Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, Shaanxi, China)
关键词:
白藜芦醇; 脂联素; 缺血/再灌注损伤; Ⅱ型糖尿病; 小鼠
Keywords:
resveratrol;  adiponectin;  ischemia/reperfusion injury;  type 2 diabetes mellitus
分类号:
R587.1
DOI:
-
文献标识码:
A
摘要:
目的:探讨白黎芦醇(RSV)减轻Ⅱ型糖尿病(T2DM)小鼠心肌缺血/再灌注损伤(MI/RI)的作用及其机制。方法： 采用喂养高脂饮食结合小剂量链脲佐菌素(STZ)建立T2DM小鼠模型。造模成功后立即给予RSV(10mg/kg)每日1次灌胃，连续3周。实验分为正常假手术组、正常手术对照组、DM假手术组、DM手术对照组、RSV组、CpC组，每组20只。手术方式采用心脏冠状动脉左前降支结扎30 min、再灌注3 h或24 h。抑制剂组于术前1 h腹腔注射Compound C（20 mg/kg）。用TTC染色法检测心肌梗死(MI)面积，TUNEL法检测心肌细胞凋亡，ELISA法检测caspase-3活性、血浆脂联素（APN）水平，Western blot法检测AMPK、p-AMPK及脂肪组织APN的含量。结果： 喂养高脂饮食结合小剂量STZ能够成功建立T2DM小鼠模型。与DM手术对照组相比，RSV饲喂能够减轻T2DM小鼠MI/RI，减小MI面积、减少心肌细胞凋亡（P<0.01），降低caspase-3的活性（P<0.05）。RSV还能够上调脂肪组织APN表达，逆转T2DM小鼠低APN血症（P<0.01）。AMPK抑制剂Compound C可显著减弱RSV的心肌保护作用（P<0.05）。结论： RSV可通过逆转T2DM小鼠的低脂联素血症，在MI/RI时发挥对心肌的保护作用。
Abstract:
AIM:To observe whether resveratrol (RSV) attenuates myocardial ischemia/reperfusion injury (MI/RI) in type II diabetes mellitus (T2DM) and, if so, to further investigate the underlying mechanisms. METHODS: T2DM was induced by a high-fat diet (HD) plus low-dose i.p. streptozotocin (STZ) injection. Mice were treated with 10 mg/kg RSV daily by intragastric administration for 3 weeks after acknowledgement of T2DM. Mice were divided into six groups: sham group, I/R group, T2DM sham group, T2DM+I/R group, RSV group, and CpC group. After 30 min ischemia by slip-knot ligature of the left anterior descending coronary artery, myocardium was reperfused for 3 h after knot release (for apoptosis by TUNEL, caspase-3 activity by ELISA) or 24 h (for infarct size determination by TTC staining). At 1 h before MI/RI, compound C (an AMPK inhibitor) was administered i.p. (20 mg/kg). RESULTS: HD feeding plus low-dose STZ injection successfully induced T2DM. RSV alleviated MI/RI in diabetic mice as evidenced by decreased infarct size, cardiomyocyte apoptosis (P<0.01) and caspase-3 activity (P<0.05). RSV treatment also improved APN level both in plasma and adipose tissue in diabetic mice (all P<0.01). Conversely, administration of AMPK inhibitor compound C significantly attenuated the cardioprotective effects of RSV (all P<0.05). CONCLUSION: RSV upregulates adiponectin levels in both plasma and adipose tissue in T2DM, thus attenuating MI/RI.

参考文献/References

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备注/Memo

备注/Memo:
收稿日期：2011-11-17. 基金项目：国家高技术研究发展计划项目资助（2009AA02Z104）；国家重大新药创制计划项目资助（2009ZX09103-673）；国家自然科学基金面上项目资助（81170186） 通讯作者：王海昌，主任医师，主要从事冠心病的研究 Email:wanghc@fmmu.edu.cn 共同通讯作者：陶凌，主任医师，主要从事糖尿病心肌缺血再灌注损伤的研究Email:lingtao2006@gmail.com 作者简介：杨强，硕士生 Email:str_yq03@163.com
更新日期/Last Update: 2012-05-02