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长期胰岛素治疗对Ⅰ型糖尿病小鼠血浆和心肌脂联素水平的影响(PDF)

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2011年第3期
页码:
289-294,299
栏目:
基础研究
出版日期:
2011-05-12

文章信息/Info

Title:
Effect of long-term insulin treatment on plasma and cardiac adiponectin levels in streptozotocin-induced diabetic mice
作者:
裴海峰马彦卓刘少伟司瑞冯世栋陶凌王海昌
第四军医大学西京医院心内科,陕西 西安 710032
Author(s):
PEI Hai-feng MA Yan-zhuo LIU Shao-wei SI Rui Feng Shi-dong TAO Ling WANG Hai-chang
Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, Shaanxi, China
关键词:
Ⅰ型糖尿病胰岛素脂联素缺血/再灌注损伤小鼠
Keywords:
type I diabetes insulin adiponectin ischemia/reperfusion injury
分类号:
R587.1
DOI:
-
文献标识码:
A
摘要:
目的:研究Ⅰ型糖尿病(DM)小鼠血浆和心肌脂联素(APN)的水平随病程进展而变化的趋势,观察长期胰岛素治疗对血浆和心肌APN水平的影响,探讨心肌局部的APN在抗心肌缺血/再灌注损伤(I/RI)中可能的作用机制。方法: 将72只雄性昆明种小鼠随机分为:正常对照组,Ⅰ型DM组和胰岛素治疗组。建立Ⅰ型DM小鼠模型,疾病组小鼠腹腔注射链脲菌素溶液,50 mg/(kg·day),连续注射5 d,而后观察5 d。于建模后1、7、14 d3个不同时间点,收集血浆用ELISA法测APN的水平;分离左心室用qRT-PCR法测APN mRNA的水平。为验证心肌局部APN水平变化的意义,选取建模后14 d各组的部分小鼠做离体心脏灌流,用末端脱氧核苷酸转移酶介导的dUTP缺口末端标记技术(TUNEL)染色检测细胞的凋亡。结果: 与正常对照组相比,Ⅰ型糖尿病组小鼠血浆APN的水平先升高后降低[建模后7 d(D7)为:(5.23±1.05) mg/L vs. (3.45±0.51) mg/L,P<0.01];心肌中APN mRNA的水平逐渐降低[D7:(0.50±0.19) vs.(1.76±0.26),P<0.05;D14:(0.10±0.05) vs.(1.77±0.41),P<0.01]。与Ⅰ型DM组相比,胰岛素治疗组小鼠血浆APN的水平明显升高[D14:(3.61±0.71) mg/L vs.(2.16 ± 0.49) mg/L,P<0.05];心肌APN mRNA的水平明显升高[D7:(1.41±0.19) vs.(0.50±0.19),P<0.05;D14:(0.80±0.17) vs.(0.10±0.05),P<0.05]。经离体心脏I/R,Ⅰ型DM组较正常对照组小鼠心肌梗死的面积及凋亡率均显著增加(P<0.01),胰岛素治疗能够显著减少Ⅰ型DM组小鼠心肌梗死的面积和凋亡率(P<0.01);而APN下游信号分子腺苷-磷酸激活的蛋白激酶(AMPK)的抑制剂化合物C(Compound C)可以部分地减弱长期胰岛素的治疗作用(P<0.01)。结论: Ⅰ型DM组小鼠血浆APN的水平随病程进展先升高后降低;而其心肌APN的水平逐渐降低,变化的趋势不同于血浆APN的水平。长期胰岛素治疗能够升高血浆和心肌局部APN的水平;而心肌局部APN水平的升高可能会增强心肌对I/RI的耐受性。
Abstract:
AIM:To investigate the time-course change of plasma and cardiac adiponectin levels in streptozotocin (STZ)-induced diabetic mice, to determine the effect of insulin treatment on plasma and cardiac adiponectin levels and to discuss the possible mechanism of cardiac adiponectin in the protection against myocardial ischemia/reperfusion injury. METHODS: Seventy-two male mice were randomly assigned to control, type 1 diabetes and insulin treatment groups. Adiponectin levels in plasma and cardiac tissues were longitudinally detected at days 1, 7, and 14 after STZ-induced diabetes was confirmed through ELISA and qRT-PCR, respectively. To examine the changes of cardiac-derived adiponectin levels, hearts were isolated and perfused in a Langendorff preparation and then stained by TUNEL. RESULTS: Compared with control mice, plasma adiponectin level in type 1 diabetic mice increased at day 7 but decreased at day 14 [D7: (5.23±1.05) mg/L vs. (3.45±0.51) mg/L, P<0.01]. Adiponectin mRNA level lowered gradually [D7: (0.50±0.19) vs.(1.76±0.26), P<0.05]; [D14: (0.10±0.05) vs.(1.77±0.41), P<0.01]. Compared with type 1 diabetic mice, plasma adiponectin level in insulin-treated mice was elevated [D14: (3.61±0.71) vs. (2.16±0.49), P<0.05] and adiponectin mRNA levels in cardiomyocytes were also elevated [D7: (1.41±0.19) vs.(0.50±0.19), P<0.05]; [D14: (0.80±0.17) vs.(0.10±0.05), P<0.05]. After ischemia/reperfusion, cardiac infarct size and cardiomyocyte apoptosis in type 1 diabetic mice markedly increased when compared with control mice (P<0.01). Long-term insulin treatment decreased infarct sizes and cardiomyocyte apoptosis in hearts of type 1 diabetic mice (P<0.01). Compound C, an inhibitor of adiponectin downstream signaling molecule AMPK, partially attenuated the effect of long-term insulin treatment (P<0.01). CONCLUSION: Plasma adiponectin levels in type 1 diabetic mice show a bidirectional change throughout the course of the disease. In cardiac tissues, local adiponectin level gradually decreases. Long-term insulin treatment may increase both plasma and local cardiac adiponectin levels. Increase of cardiac adiponectin may increase the tolerance of cardiomyocytes against ischemia/reperfusion injury.

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备注/Memo

备注/Memo:
收稿日期:2010-07-14.通讯作者:陶凌,教授,主要从事心脏缺血/再灌注损伤的机制研究 Email:lingtao2006@gmail.com 共同通讯作者:王海昌,主任医师,主要从事心律失常研究Email:wanghc@fmmu.edu.cn 作者简介:裴海峰,硕士生Email:songzhi_p@sina.com
更新日期/Last Update: 2011-03-17