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《慢性病学杂志》[ISSN:1674-8166/CN:11-5900/R]

卷:

期数:

2014年06期

页码:

421-426

栏目:

论著

出版日期:

2014-07-30

文章信息/Info

Title:

Protective effects of ascorbic acid and N-acetylcysteine on myocardial ischemia-reperfusion injury in diabetes rats

作者:

方金燕;  詹建伟;  王弋

杭州市第一医院EICU ，浙江杭州310000

Author(s):

FANG Jin-yan;  ZHAN Jian-wei;  WANG Yi

EICU,The First Hospital of Hangzhou, Hangzhou, Zhejiang 310000, China Corresponding author: WANG Yi, E-mail: wangyi060@yeah.net

关键词:

一氧化氮合酶; 四氢生物蝶呤; 糖尿病; 心肌缺血再灌注损伤

Keywords:

Nitric oxide synthase (NOS);  Tetrahydrobiopterin;  Diabetes mellitus (DM);  Ischemia-reperfusion injury

分类号:

R541.4

DOI:

-

摘要:

目的观察维生素C （AA） 和N-乙酰半胱氨酸（NAC） 对糖尿病大鼠心肌缺血再灌注损伤的影 响。方法50 只大鼠随机分为10 组，非糖尿病对照组，非糖尿病+AA 组，非糖尿病+NAC 组，非糖尿 病+ NAME 组， 糖尿病对照组， 糖尿病+ AA 组， 糖尿病+ NAC 组， 糖尿病+ NAME 组， 糖尿病+ AA + NAME 组，糖尿病+NAC+NAME 组，每组5 只大鼠。大鼠腹腔注射链脲霉素（STZ） 连续5 d，制造大 鼠糖尿病模型，对照组注射PBS。28 d 后大鼠处死取出心脏，制作离体缺血再灌注模型，在缺血再灌注前 按分组分别给以AA、NAC 和L-NAME，心脏缺血30 min 后再灌住120 min。实验后去大鼠心脏组织测 量心肌谷胱甘肽（GSH/GSSG）、生物蝶呤（BH4/BH2）、超氧化物、硝基酪氨酸（NT）、氮氧化物 （NOx） 和心肌梗死面积的变化。组间比较用单因素方差分析。结果AA 和NAC 显著提高了糖尿病大鼠 心脏的BH4/BH2 比率，降低了超氧化合物含量和硝基酪氨酸（NT） 含量，提升了氮氧化物（NOx） 产 量。在缺血再灌注前预先给以AA 和NAC 可以提高糖尿病大鼠的左心室（LV） 功能并且减小梗死面积。 在非糖尿病大鼠中则没有效果。一氧化氮合成酶抑制剂（L- NAME） 抑制超氧化物、NT 和NOx 的产 生，使糖尿病大鼠LV 功能恶化并且增加梗死面积。L-NAME 也可以抵消由AA 和NAC 增加NOx 对提高 LV 功能和限制梗死面积的效果。结论使用AA 和NAC 提高了糖尿病大鼠心脏的BH4/BH2 比率并且防 止NOS 解偶联，增加了一氧化氮的生物利用率，可以对糖尿病大鼠心脏的缺血再灌注损伤进行有效保护。

Abstract:

Objective To evaluate the effects of Ascorbic Acid (AA) and N- acetylcysteine (NAC) on ischemia-reperfusion induced myocardial injury in diabetic rats. Methods Fifty rats were randomly divided evenly into ten groups: non-diabetic control group, group of non-diabetic rats treated with AA, group of non-diabetic rats treated with NAC, group of non-diabetic rats treated with Nω-nitro-L-Arginine Methyl Ester (L-NAME), diabetic control group, group of diabetic rats treated with AA, group of diabetic rats treated with NAC, group of diabetic rats treated with L-NAME, group of diabetic rats treated with AA combined with L-NAME, group of diabetic rats treated with NAC combined with LNAME. There were 5 rats in every group. Rats were intraperitoneally injected with Streptozotocin (STZ) for 5 days in the diabetes groups to induce Diabetes Mellitus, and the rats from the control group were injected with Phosphate-Buffered Saline (PBS). Twenty-eight days after injection, the rats were sacrificed, and the rats’ hearts were isolated and perfused with Krebs- Henseleit bicarbonate(KHB) buffer solution for 30 mins. Afterwards, the hearts were treated with AA, NAC or NAME for 30 mins followed by 30 mins ischemia and 2hs reperfusion. Myocardial GSH/GSSG ratio, myocardial BH4/BH2 ratio, superoxide production, nitrotyrosine (NT), NOx and infarct size were measured after the treatments. Univariate analysis was compared among different groups. Results Treatments with AA or NAC significantly increased BH4/BH2 ratio in the diabetic hearts, decreased the production of superoxide and NT, and increased generation of NOx. Pre-treatment with AA or NAC before 30 mins ischemia followed by 120 mins reperfusion improved left ventricular function and reduced infarct size in the diabetic groups, but didn’t show effects among non-diabetic groups. The Nitric Oxide Synthase (NOS) inhibitor L-NAME restrained the generation of superoxide, NT and NOx, but aggravated left ventricular function and increased infarct size in the diabetic hearts. L- NAME also abrogated the increase in NOx caused by AA and NAC, and improved left ventricular function and the infarct size-limiting effects. Conclusions These results suggest that AA and NAC can increase BH4/BH2 ratio and prevent NOS uncoupling in the diabetic hearts, and have protective effects on bioavailability of NO renders the diabetic heart tolerant to Ischemia-Reperfusion injury.

参考文献/References:

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备注/Memo

备注/Memo:

基金项目：浙江省科技计划项目（2012C37104） 作者简介：方金燕，本科，主治医师，长期从事重症医学的研究和临床工作 通信作者：王弋，E-mail：wangyi060@yeah.net

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更新日期/Last Update: 2014-07-30