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GSNO在糖尿病和非糖尿病小鼠心肌缺血/再灌注损伤中的作用

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2011年第2期
页码:
146-150
栏目:
基础研究
出版日期:
2010-12-10

文章信息/Info

Title:
Different effects of S-nitrosoglutathione (GSNO) on myocardial ischemia reperfusion injury in diabetic and non-diabetic mice
作者:
夏陈海; 贺媛; 王汝涛; 靳温; 刘毅;  陶凌; 王海昌
第四军医大学西京医院心脏内科，陕西 西安 710032
Author(s):
XIA Chen-hai;  HE Yuan;  WANG Ru-tao;  JIN Wen;  LIU Yi;  TAO Ling;  WANG Hai-chang
Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, Shaanxi, China
关键词:
心肌缺血/再灌注; 心肌梗死; 糖尿病; S-亚硝基谷胱甘肽; 小鼠
Keywords:
myocardial ischemia-reperfusion;  myocardial infarction;  diabetes;  GSNO;  mice
分类号:
R587.1
DOI:
-
文献标识码:
A
摘要:
目的: 探讨NO供体S-亚硝基谷胱甘肽(GSNO)在糖尿病(DM)小鼠和非DM小鼠心肌缺血/再灌注（MI/R）损伤中的作用。方法： 120只雄性昆明小鼠随机分为6组，每组20只。即假手术组(Sham)组、DM+sham组、MI/R+媒介物(Vehicle)组、DM+MI/R+Vehicle组、MI/R+GSNO组及DM+MI/R+GSNO组，使小鼠心肌缺血30 min、再灌前10 min，腹腔注入100 μmol/L的GSNO溶液或等体积的生理盐水(NS)。再灌3 h后，用ELISA法检测NOx、硝基酪氨酸(N-Tyr)的含量及caspase-3的活性。使用试剂盒检测超氧阴离子（O-2）的含量。用TUNEL法检测心肌细胞的凋亡，再灌注24 h，用TTC法检测心肌梗死的面积。结果： ①与sham组的O-2含量［(2.02±0.21) RLU/(mg·s)］相比，DM+sham组O-2的含量［(2.76±0.21) RLU/(mg·s)］明显增加（P<0.05）。②与MI/R+媒介物组相比，MI/R+GSNO组的梗死面积明显减少［(50.4±3.32)% vs.(37.0±4.37)%，P<0.05］、心肌细胞凋亡明显减少［(60.0±5.47)% vs.(44.2±2.28)%，P<0.05］，caspase-3的活性明显降低［(47.6±4.47) nmol/(h·mg蛋白)］ vs.(34.6±1.80) nmol/(h·mg蛋白)，P<0.05］，N-Tyr的含量明显减少［(0.91±0.16) μg/mg蛋白］ vs.(0.54±0.083) μg/mg蛋白，P<0.05］，NOx的含量明显增加［(1.14±0.063) μmol/g蛋白 vs.(1.84±0.045) μmol/g蛋白，P<0.01］。③与DM+MI/R+媒介物组相比，DM+MI/R+GSNO组的梗死面积显著增加［(64.2±2.35)% vs.(85.6±2.80)%，P<0.01］，心肌细胞的凋亡显著增加［(78.0±2.47)% vs.(87.6±1.93)%，P<0.05］，caspase-3的活性显著增加［(62.17±3.24) nmol/(h·mg蛋白) vs.(77±2.09) nmol/(h·mg蛋白)，P<0.01］，N-Tyr的含量明显增加［(1.47±0.16) μg/mg蛋白 vs.(2.06±0.18) μg/mg蛋白，P<0.05］，NOx的含量显著增加［(1.51±0.11) μmol/g蛋白 vs.(2.24±0.18) μmol/g蛋白，P<0.05］。结论： GSNO可以减轻非DM小鼠MI/R损伤，但可加重DM小鼠MI/R损伤,其机制可能与DM心肌组织中氧化应激水平增加有关。
Abstract:
AIM: To detect the effects of S-nitrosoglutathione (GSNO) on myocardial ischemia reperfusion injury in diabetic and non-diabetic mice. METHODS: One hundred and twenty male mice were divided into six groups: control+sham, DM+sham, control+MI/R+vehicle, DM+MI/R+vehicle, control+MI/R+GSNO, and DM+MI/R+GSNO. Mice were anesthetized with 2% isoflurane and myocardial ischemia was produced by temporarily exteriorizing the heart via a left thoracic incision and placing a 6-0 silk suture slipknot around the left anterior descending coronary artery. Ten minutes before reperfusion, mice were randomized to receive vehicle or GSNO. After 30 min of ischemia, the slipknot was released and the myocardium was reperfused for 3 h (for NOx contents, nitrotyrosine content and caspase-3 activity by ELISA, O-2 contents by frozen section and apoptosis by TUNEL) or 24 h (for infarct size by TTC). RESULTS: Compared with those in group of control+sham, the contents of O-2 increased in group of DM+sham (P<0.05). Compared with those in group of control+MI/R+vehicle, the infarct size (P<0.05), myocardial apoptosis (P<0.05), caspase-3 activity (P<0.05) and the contents of nitrotyrosine (P<0.05) reduced, and the contents of NOx increased (P<0.01) in control group+MI/R+GSNO. Compared with those in group of DM+MI/R+vehicle, infarct size (P<0.01), myocardial apoptosis (P<0.05), caspase-3 activity (P<0.01), contents of nitrotyrosine (P<0.05) and NOx (P<0.05) increased in group of DM+MI/R+GSNO. CONCLUSION: GSNO reduces MI/R injury in non-diabetic mice but increases MI/R injury in diabetic mice.

参考文献/References

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备注/Memo

备注/Memo:
收稿日期：2010-06-11.基金项目：国家自然科学基金项目资助（30670879）；西京医院助推项目资助（XJZT08Z02） 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，副主任医师，主要从事糖尿病心肌缺血/再灌注的研究Email:lingtao2006@gmail.com 作者简介：夏陈海，硕士生Email:xiachenhai-204@163.com
更新日期/Last Update: 2010-12-10