低分子肝素对大鼠肾缺血再灌注损伤时ICAM-1及MCP-1表达的影响

Low molecular weight heparin therapy in rats on renal ischemia reperfusion injury: related to the expression of nephridial tissue intercellular adhesion molecular-1 and monocyte chemoattractant protein -1

目的探讨低分子肝素(LMWH)对大鼠肾缺血再灌注(IRI)损伤的作用机制。方法将80只健康Wistar大鼠随机分为正常对照组、假手术组、模型组及治疗组各10只,后两组建立IRI模型并于再灌注前5min阴茎静脉内分别注射500U/kg LMWH及等量生理盐水。结果造模后1、3、6、24h模型组血清肌酐(SCr)水平、中性粒细胞(PMNs)细胞间黏附分子-1(ICAM-1)表达、肾小管损伤积分及肾组织单核细胞趋化蛋白-1(MCP-1)表达水平均明显高于对照组及假手术组,治疗组上述指标均明显低于模型组(P均<0·05)。肾组织中MCP-1表达与肾小管损伤积分呈良好相关性(r=0·71,P<0·01);MCP-1与ICAM-1呈显著正相关(r=0·62,P<0·05)。结论ICAM-1、MCP-1与肾损伤的发生密切相关;LMWH可能通过减少ICAM-1及MCP-1的表达抑制炎症反应过程,减轻肾组织损伤。

Objective To approach the effect of low molecular weight heparin （LMWH） on rat renal ischemia reper- fusion injury by observing the expression of intercellular adhesion molecular-1 （ ICAM-1 ） and monocyte chemoattractant pro- tein-1 （ MCP-1 ） in renal heterophil granulocytes. Methods To establish the model for rat renal ischemia rcperfusion inju- ry, 80 healthy Wistar rats were equally randomized into the following groups： the blank control group, the sham-operated control group, the IRI control group and the LMWH treatment group. The latter two groups were stratified according to the post operating observation periods. Levels of blood serum creatinine （SCr） and the variation of intercellular adhesion mo- lecular-1 （ ICAM-1 ） of polymorphonuclear neutrophils （PMNS） were tested in each group. Light microscopes and immuno- histochemical methods were used to observe the histomorphology of nephridial tissue and the expression of MCP-1. Results ①1 h after reperfusion, levels of ICAM-1, MCP-1 were increased and the score of renal tubular necrosis was significantly increased when compared with that of the sham-operated control group although the level of SCr has no marked change. ②6 h after reperfusion, the concentration of serum creatine in both the IRI group and the treatment group were significantly increased. However, in the LMWH treatment group, the levels of serum SCr, ICAM-1 and MCP-1 were significantly de- creased when compared with that of the IRI control group. ③Correlation analysis shows that there was a significant correla- tion between MCP-1 and the score of renal tubular injury. Also, MCP-1 had a significant positive correlation with ICAM-1. Conclusions Pristine transient expression of ICAM-1 and MCP-1 in IRI may coordinate with the injury of nephridial tis- sue. LMWH may decrease the expression of ICAM-1 and MCP-1, repress the inflammatory reaction and mitigate.