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高血糖促进氧化应激加重大鼠心肌缺血/再灌注损伤(PDF)

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2012年第3期
页码:
308-311,319
栏目:
基础研究
出版日期:
2012-06-25

文章信息/Info

Title:
Hyperglycemia aggravates ischemia/reperfusion myocardial injury in rats through increased oxidative stress
作者:
苏 慧1; 邢文娟2; 张海锋3; 王晓明1; 张荣怀1; 高 峰2; 孙 新4
(第四军医大学：1.西京医院老年病科,2.基础部生理学教研室,3.基础医学教学实验中心,4.西京医院儿科，陕西 西安 710032)
Author(s):
SU Hui1;  XING Wen-juan2;  ZHANG Hai-feng3;  WANG Xiao-ming1;  ZHANG Rong-huai1;  GAO Feng2;  SUN Xin4
(1.Department of Geriatrics, 4.Department of Pediatrics, Xijing Hospital, 2.Department of Physiology, 3.Center of Teaching Experiments, School of Basic Medical Sciences, Fourth Military Medical University, Xi’an 710032, Shaanxi, China)
关键词:
高血糖; 心肌缺血/再灌注损伤; 氧化应激; 硫氧还蛋白结合蛋白
Keywords:
hyperglycemia;  myocardial ischemia/reperfusion injury;  oxidative stress;  Txnip
分类号:
R587.1
DOI:
-
文献标识码:
A
摘要:
目的:研究高血糖是否可通过增加大鼠急性缺血/再灌注（I/R）心肌氧化应激而加重心肌损伤，并探讨其机制。方法： 将SD大鼠随机分为3组：假手术组(Sham)、生理盐水对照组(Vehicle)和高糖组(HG)。通过缺血30 min再灌注6 h，建立大鼠急性心肌I/R模型。通过静脉输注高浓度葡萄糖溶液，建立大鼠急性心肌I/R并发高血糖动物模型。术中监测血糖水平。再灌注结束后，检测血浆心肌酶谱水平，心肌梗死面积（IS）、心肌细胞凋亡指数（AI）和caspase 3的活性，检测心肌组织中氧化应激指标超氧阴离子、gp91phox、MDA、SOD，以及硫氧还蛋白结合蛋白（Txnip）的水平和硫氧还蛋白（Trx）的活性。结果： 与Vehicle组比较，HG组大鼠血糖水平显著升高，肌酸激酶（CK）、乳酸脱氢酶（LDH）的水平和IS增加，AI和caspase 3的活性升高(P<0.05)。HG组I/R心肌组织氧化应激程度显著升高，超氧阴离子、gp91phox和MDA水平增加(P<0.05)。同时，HG组I/R心肌组织的Txnip表达增加而Trx活性降低(P<0.05)。结论： 高血糖可增加大鼠I/R心肌中Txnip的表达，抑制Trx的活性促进氧化应激，这可能是其加重I/R心肌损伤的机制。
Abstract:
AIM:To study the effects of hyperglycemia on oxidative stress and ischemia/reperfusion (I/R) myocardial injury in rats and the possible mechanisms. METHODS: Rats were subjected to 30 min of myocardial ischemia and 6 h of reperfusion and were randomly assigned to sham group, vehicle group (saline throughout ischemia and reperfusion period) or high glucose (HG) group (administration of 500 g/L glucose by i.v. infusion during ischemia and reperfusion period). Blood glucose levels were monitored throughout the experiments. Myocardial infarct size (IS) and serum myocardial enzymogram of rats were determined after the experiments. Apoptotic index (AI), caspase 3 activity, thioredoxin-interacting protein (Txnip) protein level and thioredoxin (Trx) activity were detected in I/R rats and were determined after the experiments. Apoptotic index, caspase 3 activity, superoxide, gp91phox, malondialdehyde (MDA), superoxide dismutase (SOD), and Txnip protein level of myocardium were also detected. RESULTS: Compared with vehicle group, HG group had significantly enlarged infarct size as well as increased creatine kinase, lactate dehydrogenase levels, AI and caspase 3 activity (P<0.05). At the same time, hyperglycemia increased oxidative stress as expressed by increased superoxide, gp91phox and MDA (P<0.05). Hyperglycemia increased Txnip protein expression in ischemia/reperfusion myocardium and decreased Trx activity. However, Trx protein was not affected. CONCLUSION: Hyperglycemia induces Txnip expression and decreases Trx activity in I/R myocardium. The resultant increased oxidative stress may be one of the mechanisms responsible for the exacerbated rat I/R myocardial injury induced by hyperglycemia.

参考文献/References

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备注/Memo

备注/Memo:
收稿日期：2011-11-06.基金资助：国家自然科学基金项目资助（30800471；30800376）；陕西省自然科学基金项目资助（SJ08-ZT11-51） 通讯作者：孙新，副主任医师，主要从事心血管疾病的基础与临床研究 Email：sunxin6@fmmu.edu.cn 作者简介：苏慧，副主任医师，博士 Email：huisu5016@yahoo.com.cn
更新日期/Last Update: 2012-05-02