肝细胞生长因子对肿瘤坏死因子α及放线菌素D所致大鼠心肌细胞凋亡的影响  

Effect of hepatocyte growth factor on myocardial cell apoptosis induced by tumor necrosis factor-α and actinomycin D

作　　者：姚渭清[1] 宓越群[1] 王莹[1] 王荣发[1] 陈玲[1] 陈树宝[1] 

机构地区：[1]上海交通大学医学院附属新华医院上海儿童医学中心,上海200092

出　　处：《中国小儿急救医学》2006年第5期454-456,共3页Chinese Pediatric Emergency Medicine

摘　　要：目的探讨肝细胞生长因子(HGF)对肿瘤坏死因子(TNF)α及放线菌素D作用下的大鼠心肌细胞凋亡特性的影响及其信号机制,以寻求全身性感染及感染性休克状态下保护心肌细胞的新手段。方法通过流式细胞术、荧光显微镜技术及原位细胞凋亡检测,观察HGF(终浓度分别为10、30、100 ng/ml)对TNF-α(终浓度为5 nM)加用放线菌素D(终浓度为0.05μg/ml)所致大鼠心肌细胞凋亡模型的影响,并观察磷脂酰肌醇3激酶抑制剂LY294002(终浓度20μM)或丝裂原活化的蛋白激酶抑制剂U0126(终浓度30μM)能否阻断HGF的作用。结果HGF能够抑制放线菌素D与TNF-α共同作用下的培养大鼠心肌细胞凋亡,并呈现量效关系。与LY294002共孵育,HGF抑制凋亡的效应被阻断,而加用U0126不能阻断HGF的作用。结论HGF能够保护放线菌素D与TNF-α共同作用下的培养大鼠心肌细胞免于凋亡,且通过磷脂酰肌醇3激酶传导途径发挥作用。Objective To study the effect and signal mechanism of HGF on myocardial cell apoptosis induced by TNF-α and actinomycin D, so as to search for new method for myocardial protection in patients with sepsis and septic shock. Methods By using flow cytometry, fluorescence microscope technique and terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling （TUNEL）, the effect of HGF （with concentrations of 10, 30, 100 ng/ml） on apoptosis of cultured rat myocardial cells induced by TNF-α （5 nM） plus actinomycin D （0.05 μg/ml）were studied. Results HGF suppressed the myocytes apoptosis induced by TNF-α plus actinomycin D with dose effect relationship. Its effect could be blocked by PI3K inhibitor LY294002 （20 μM）but not by MAPK inhibitor U0126（30 μM）. Conclusion HGF exerts its anti-apoptotic effect by activating PI3K signal transduction.

关 键 词：肝细胞生长因子 心肌细胞 凋亡 信号转导 肿瘤坏死因子Α 

分 类 号：R541[医药卫生—心血管疾病]