基础医学与临床 ›› 2007, Vol. 27 ›› Issue (12): 1343-1346.

• 研究论文 • 上一篇    下一篇

无创性肢体预适应对大鼠缺血再灌注损伤心肌基质金属蛋白酶的影响

李淑娟 吴艳娜 康毅 尹永强 高卫真 刘艳霞 娄建石   

  1. 天津医科大学药理教研室 天津医科大学药理教研室 天津医科大学药理教研室 天津医科大学药理教研室 天津医科大学药理教研室 天津医科大学药理教研室 天津医科大学药理教研室
  • 收稿日期:2006-11-13 修回日期:2007-03-19 出版日期:2007-12-25 发布日期:2007-12-25
  • 通讯作者: 娄建石

Effect of nonvasive limb ischemic preconditioning on myocardium matris metalloproteinases induced by ischemia/reperfusion in rats

Shu-juan LI, Yan-na WU, Yi KANG, Yong-qiang YONG, Wei-zhen GAO, Yan-xia LIU, Jian-shi LOU   

  1. Department of Pharmacology,Tianjin Medical University
  • Received:2006-11-13 Revised:2007-03-19 Online:2007-12-25 Published:2007-12-25
  • Contact: Jian-shi LOU

摘要: 目的 观察大鼠无创性肢体缺血预适应(LIP)对心肌缺血再灌注损伤后心肌形态学、梗死面积和心肌MMP-2、MMP-9和TIMP-1的影响。方法 通过连续3 d每天1次3个循环的下肢无创性5 min缺血、5 min再灌建立LIP模型。大鼠随机分成3组,心肌缺血再灌注组(I/R)、心肌缺血预适应组(CIP)和LIP组。以HE染色法观察心肌形态学改变;红四氮唑染色法确定心肌梗死范围,IS=IA/AAR×100%;免疫组化法测定心肌MMP-2、MMP-9和TIMP-1水平。结果 缺血30 min再灌注120 min 后,I/R组IS为(44.5±8.1)%;与I/R组比较,CIP和LIP均能明显改善心肌损伤的形态学改变,降低心肌细胞的肿胀、减少间质出血和炎性细胞的浸润。CIP使IS降低35.7%,缺血区心肌MMP-2降低42.1%,MMP-9降低43.3%,TIMP-1水平增加40.0%;LIP使IS降低42.9%,缺血区心肌MMP-2降低41.2%,MMP-9降低46.6%,TIMP-1水平增加53.8%。结论 LIP不仅能改善缺血再灌注损伤大鼠心肌形态学改变、减少心肌梗死面积,而且能降低心肌细胞基质的损伤,起到保护心肌的作用。

关键词: 肢体, 缺血预适应, 心肌保护, 缺血再灌损伤, 基质金属蛋白酶

Abstract: Objective To determine whether nonivasive limb ischemic preconditioning (LIP) produces cardioprotective effect on ischemia-reperfused myocardium and to observe the roles of matris metalloproteinases (MMPs) in this effect. Methods LIP was performed in rats by a repeated three-cycle (5 min ischemia-5 min reperfusion) of hind limb everyday for three days. The rats were randomly divided 3 groups: I/R group, myocardial ischemic preconditioning (CIP) group and LIP group. The morphologic changes were observed using HE dyeing. The area at risk (AAR) and infarct area (IA) were determined using Trypan blue and triphenyl tetrazolium choride (TTC) staining respectively. The infarct size (IS) was defined as IA/AAR×100%.MMP-2、MMP-9 and TIMP-1 in different myocardial areas were determined by immunohistochemistry. Results During 30 min myocardial ischemia and subsequent 120 min reperfusion, the IS was (44.5±8.1)%. Compared with I/R, the myocardial swelling, interstitial hemorrhage and inflammatory cell infiltrate were decreased in both of CIP group and LIP group, and the IS was reduced 35.7% in CIP group and 42.9% in LIP group. The level of MMP-2, MMP-9 decreased in CIP group (42.1% and 43.3%) and LIP group was (41.2% and 46.6%) than those in I/R group, but the level of TIMP-1 increased in CIP group (40.0%) and LIP group (53.8%) than that in I/R group. CONCLUSION LIP could not only reduce the infarct area in myocardium but also prevent cardiac matrix from degrading following the myocardial ischemia-reperfusion. The MMPs play an important role in the myocardial protection provided by LIP.

Key words: limb, ischemic preconditioning, myocardium cardioprotection, ischemia/reperfusion injury, matris metalloproteinases