环氧化酶-2参与丹参酮IIA改善脓毒症大鼠的心肌凋亡  

Involvement of cyclooxygenase-2 in mechanism of tanshinone IIA action in ameliorating cardiac myocyte apoptosis in rats with sepsis

作　　者：王铮[1] 陈华文[1] 冯俊[1] 

机构地区：[1]华中科技大学同济医学院附属同济医院,湖北武汉430030

出　　处：《中国医院药学杂志》2015年第18期1629-1633,共5页Chinese Journal of Hospital Pharmacy

基　　金：国家自然科学基金(编号:81202825);湖北省自然科学基金(编号:2011CDB196)

摘　　要：目的:探讨丹参酮IIA改善脓毒症大鼠心肌凋亡的作用及可能的机制——花生四烯酸环氧化酶-2途径。方法:采用盲肠结扎穿孔术制备脓毒症大鼠模型(CLP),雄性Wistar大鼠随机分成4组:假手术组(Sham组),脓毒症组(CLP组),Tan IIA组和Celecoxib组,后两组于CLP后给予丹参酮IIA(Tan IIA)腹腔注射处理,Celecoxib组同时选用花生四烯酸环氧化酶-2的特异性抑制剂塞来昔布灌胃处理,分析治疗12 h后的心肌细胞的炎性氧化因子(TNF-α、IL-1β、MDA、SOD)含量、凋亡情况、心肌促凋亡基因(Bax、Fas、P53和Caspase-3)和抑制凋亡基因(Bcl-2)的表达情况以及左心室心肌COX-2的mRNA、蛋白表达和活性水平。结果:与Sham组相比,CLP组大鼠心肌细胞凋亡指数升高(P<0.05);COX-2的蛋白、mRNA表达水平增加、活性增强;Bax、fas、P53及Caspase-3的蛋白和mRNA表达水平上升(P<0.05),Bcl-2的蛋白和mRNA表达水平下降(P<0.05);给予丹参酮ⅡA处理的脓毒症大鼠,上述指标均有显著改善(P<0.05);在丹参酮ⅡA处理的同时给予赛来昔布干预后,上述指标水平与仅用丹参酮ⅡA处理后相似(P>0.05)。结论:丹参酮IIA对脓毒症大鼠心肌凋亡具有保护作用,可能通过花生四烯酸环氧化酶(COX-2)途径实现。OBJECTIVE To explore effects of tanshinone IIA（Tan IIA）on cardiac myocyte apoptosis in rats with sepsis and possible mechanism of cyclooxygenase pathway.METHODS Sepsis was reproduced in rats by cecum ligation and puncture（CLP）.Rats were randomly divided into sham operation group,CLP model group,Tan IIA group and celecoxib group.Animals in two latter groups were intraperitoneally administered Tan IIA after establishment of CLP model.Meanwhile,animals in celecoxib group were intragastically given celecoxib,a specific inhibitor of cyclooxygenase-2（COX-2）.Rats were sacrificed 12 hours after CLP,animal hearts were removed to detect cytokines（TNF-α,IL-1β,MDA,SOD）,cardiac apoptosis,pro-apoptotic genes（Bax,Fas,P53 and caspase-3）,anti-apoptotic gene（Bcl-2）,activity and expression of mRNA and protein of COX-2.RESULTS Compared with sham operation group,apoptosis index in septic rats was increased（P〈0.05）.Moreover,expression of COX-2 mRNA and protein and their activities were elevated.Expression levels of Bax,fas,P53 and caspase-3 mRNA and protein were up regulated（P〈0.05）,expression levels of Bcl-2 protein and mRNA were down regulated（P〈0.05）.In septic animals treated by Tan IIA,the above mentioned indicators were significantly improved（P〈0.05）.After treatment with Tan IIA and then with celecoxib,results were similar to those after treatment with Tan IIA alone（P〉0.05）.CONCLUSION Tan IIA can protect cardiac myocytes from apoptosis in septic rats and protective action might be accomplished via COX-2 pathway.

关 键 词：丹参酮IIA 环氧化酶-2 脓毒症 心肌凋亡 

分 类 号：R969[医药卫生—药理学]