三七总皂甙对肺缺血再灌注损伤时细胞凋亡及Fas/FasL的影响

Effects of panax notoginseng saponins on pneumocyte apoptosis and Fas/FasL expression in rabbits with lung ischemia/reperfusion injury

目的:探讨细胞凋亡与肺缺血再灌注损伤的关系以及三七总皂甙的作用及机制。方法:健康日本大耳白兔84只,随机分为对照组、肺缺血再灌注1、3、5h组和三七总皂甙干预1、3和5h组。复制肺缺血再灌注损伤模型。采用原位缺口末端标记(TUNEL)法观测肺组织细胞凋亡指数,免疫组化和原位杂交技术检测肺组织细胞Fas/FasL系统蛋白和基因表达的变化。结果:肺缺血再灌注组肺组织细胞凋亡指数和Fas/FasL蛋白及基因表达均显著高于对照组(均P<0.01)。三七总皂甙干预组Fas/FasLmRNA及其蛋白质的表达显著低于缺血再灌注组(P<0.01),肺组织细胞凋亡指数也显著低于缺血再灌注组(P<0.01)。肺组织细胞凋亡指数分别与Fas/FasL蛋白和Fas/FasLmRNA之间均呈显著正相关(r分别=0.540,0.658,0.668,0.686;均P<0.01)。结论:Fas/FasL系统活化启动的肺组织细胞凋亡可能参与了肺缺血再灌注损伤的发生。三七总皂甙可能通过抑制Fas/FasL系统的激活,阻遏肺组织细胞凋亡,从而减轻肺缺血再灌注损伤。

AIM： AIM： To explore the relationship between apoptosis in the lung tissues and lung ischemia/reperfusion injury, anti observe effects of panax notoginseng saponins （PNS） on apoptosis in lung iseheroia/reterfusion injury. METHODS： Single lung in situ ischemia/reperfusion animal model was used. Eighty four Japanese white rabbits were randomly divided into control group （control）, ischenmia/reperfusion 1 h group （IR1h）, IR3h, IR5h, Panax Notoginseng Saponins 1 h group （PNS1h）, PNS3h and PNS5h. TUNEL, inmmunocytochemistry and in situ hybridization and in situ hybridization techniques were used to observe apoptosis and Fas/ FasL expression in various phases of lung ischemia/reperfusion. RESULTS： Cell apoptosis in lung tissues were significant ly high, Fas/FasL mRNA and its protein were up- regulated in lung tissues of lung ischemia/reperfusion injury compared with control （all of P 〈 0.01 ）. The PNS suppressed apoptosis as well as expression of Fas/FasL mRNA and its protein （ P 〈 0.05 or P 〈 0.01, respectively）. There was a significant correlation between expression of Fas/FasL protein, Fas/FasL mRNA and cell apoptosis （ r = 0.540,0.658,0.668,0.686;all P 〈 0.01 ）. CONCLUSIONS： Activation of Fas/FasL system and its initiating cell apoptosis of lung tissues may contribute to the pathogenesis of lung ischemia/reperfusion injury. The protective effects of PNS include suppressing the activation of Fas/FasL system and blocking apoptosis in hmg tissues in lung ischemia/reperfusion injury.