三七总皂甙对心肌缺血-再灌注中中性粒细胞浸润的影响及其核转录机制的实验研究

目的 研究三七总皂甙心肌缺血-再灌注时中性粒细胞（PMN）内核因子-kB(NF-kB)活性变化，细胞间粘附分子（ICAM-1）表达及中性粒细胞浸润的影响。方法 新西兰兔124只随机分为以下3组；（1）缺血-再灌注组（IR）；结扎兔左冠状动脉前降支造成心肌缺血45min后再开放；（2）三七总皂甙（PNS）预处理组（IR PNS）：在心肌缺血前10min静脉注射PNS（100mg/kg)；（3）假手术对照组；每组又分缺血前，再灌注后30、60、90、120、240、360min时相点。用流式细胞仪检测中性粒细胞ICAM-1的表达；用凝胶电泳迁移率分析检测NF-kB的活性；用髓过氧化酶法（MPO）定量测定心肌组织中浸润的中性粒细胞。结果 在缺血-再灌注组中心肌再灌注30min后NF-kB活性开始增高，120min达到高峰，之后活性下降；中性粒细胞ICAM-1的表达在心肌再灌注120min开始增高，并与中性粒细胞的心肌浸润增加有相关性；在三七总皂甙预处理组，PNS能抑制NF-kB的活化及中性粒细胞ICAM-1的表达和中性粒细胞心肌浸润，结论 心肌缺血-再灌注时能刺激中性粒细胞内NF-kB的活化，活化的NF-kB启动中性粒细胞ICAM-1的表达而参与心肌缺血-再灌注损伤的发生过程；三七总皂甙能抑制中性粒细胞内核因子-kB的活化，减少细胞间粘附分子表达及中性粒细胞浸润而起到心肌保护的作用。

Experimental Study on Effects of Total Saponins of Panax Notoginseny on Activation of NF-Kb and Infiltration of PMN in Myocardial Ischemic-reperfusion Injury

Objective:To study the Influence of total saponins of Panax Notoginseny (PNS)on Activation of nuclear factor-kB (NF-kB) and infiltration of polymorphonuclear neutriphils (PMN) in myocardial ischemic-reperfusion. Methods: one hundred and twenty four Newzeland rabbits were divided into three groups: IR group (ischemia reperfusion group): Rabbits were subjected to total occlusion 45 min of left anterior desending artery (LAD) followed reperfusion, PNS proconditioning group (IR+PNS group): PNS 100mg/kg pretreated rabbits 10 min before ischemia, and sham-group. The blood and ischemic myocardial samples were studied at before ischemia ,30,60,90,120,240,360 mins after ischemia reperfusion. The expression levels of ICAM-1 were evaluated by flow cytometry, activation of NF-kB by electrophoretic mobility shift assay (EMSA),the infiltration rate of PMN were measured by MPO . Results: In IR group, after IR 30 min, activation of NF-kB were increased significantly and reached a peak at 120 min, then decreased; the expression levels of ICAM-1 were increased at 120 min and had positive correlation to the infiltration rate of PMN. In IR+PNS, PNS could inhibit the activation of NF-kB, expression of ICAM-1 and infiltration of PMN. Conclusion: The inducible activation of NF-kB starts up ICAM-1 expression of PMN and it is an important factor in myocardial ischemic-reperfusion injury, PNS has protective effect on myocardium by inhibtion activation of NF-kB, ICAM-1 expression and infiltration of PMN.