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中国临床药理学与治疗学 ›› 2006, Vol. 11 ›› Issue (12): 1385-1388.

• 研究原著 • 上一篇    下一篇

硝酸异山梨酯对大鼠心肌后期预适应的诱导作用

王占庆1,2, 王金萍1, 许景峰1   

  1. 1北京军区总医院药理科, 北京 100700;
    2军事医学科学院毒物药物研究所, 北京 100850
  • 收稿日期:2006-08-07 修回日期:2006-10-31 出版日期:2006-12-26 发布日期:2020-11-06
  • 作者简介:王占庆, 男, 博士生, 主管药师, 研究方向:心血管药理学。Tel:010-66721604  E-mail:wangzhanqing2049@yahoo.com.cn;许景峰, 男, 教授, 主任药师, 博士生导师, 研究方向:新药研究与合理用药。Tel:010-66721260

Isosorbide dinitrate induces late preconditioning against myocardial infarction in rats

WANG Zhan-qing1,2, WANG Jin-ping1, XU Jing-feng1   

  1. 1Department of Pharmacology, General Hospital of Beijing Command of PLA, Beijing 100700, China;
    2Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing 100850, China
  • Received:2006-08-07 Revised:2006-10-31 Online:2006-12-26 Published:2020-11-06

摘要: 目的 探讨硝酸异山梨酯(ISDN) 能否诱导大鼠后期预适应及其可能机制。方法 采用大鼠在体缺血再灌注(I R) 模型, 将动物随机分为生理盐水组、ISDN 给药组、假手术组、后期缺血预适应组、生理盐水+I/R 组、ISDN +I/R 组、生理盐水+格列苯脲+I/R 组、ISDN +格列苯脲+I/R 组。前两组于给药24 h 后, 测定心肌组织中的SOD 和诱导型一氧化氮合成酶的含量, 含I R 组于给药24 h 后进行缺血40 min 再灌注1.5 h 后测心肌梗死范围、心肌组织及血清学指标。结果 ISDN 组心肌组织中诱导型一氧化氮合成酶浓度明显比生理盐水组高(P<0.01);后期缺血预适应组和ISDN +I/R 组与生理盐水+I/R 组相比, 心肌梗死面积、血清肌酸激酶和乳酸脱氢酶含量明显减少(前两者P<0.05, 后者P<0.01), 心肌组织中NO 和锰-SOD 显著增加, 丙二醛显著下降(P<0.05) 。结论 ISDN 能诱导心肌后期预适应, 其机制与NO 和诱导型一氧化氮合成酶的升高以及机体的抗氧化能力增强有关。

关键词: 硝酸异山梨酯, 缺血预适应, 诱导型一氧化氮合成酶, 锰-超氧化物歧化酶, 大鼠

Abstract: AIM: To determine whether isosorbide dinitrate (ISDN) could induce late ischemic preconditioning in rats.METHODS: SD rats were divided into oral normal saline (control group), oral ISDN (0.2mg·kg-1, ISDN group), SHAM grouP;oral normal saline combined with ischemia and reperfusion(I/R) (I/R control group), ISDN plus I/R group, ISDN plus Gly plus I/R group, Gly plus I/R control grouPand late ischemic preconditioning grouP(3 cycles of 5-min coronary occlusion 5-min reperfusion, LPC group).24 h later,rats, like other groups with I/R, were underwent a 40 min coronary occlusion followed by 1.5 h of reperfusion.RESULTS: Myocardial infarct size and the levels of creatine kinase (CK) in serum were significantly reduced after pretreated with ISDN +I/R versus I R control group(P<0.05), so was lactate dehydrogenase (LDH) (P<0.01).Nitric oxide and Mn-superoxide dismutase in heart tissue were significantly elevated, while MDA was significantly reduced (P<0.05).The level of induced nitric oxide synthetase (iNOS) in heart tissue was significantly elevated in the ISDN grouPcompared with controls(P<0.01).CONCLUSION: ISDN induces delayed cardioprotection against myocardial infarction similar to that afforded by the late phase of ischemic PC, possibly by up-regulating NO and iNOS, and strengthening antioxidant mechanism.

Key words: isosorbide dinitrate, ischemic preconditioning, induced nitric oxide synthetase, Mn-superoxide dismutase, rat

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