眼镜蛇毒NGF通过PI3K/Akt促人肝星状细胞凋亡的机制研究  

Effect of cobra venom NGF on inducing apoptosis of LX2 cells by inhibiting Akt signaling pathway and its mechanism

作　　者：蔡凤桃 张学荣[1] 孙林[1] 王秀男[1] 廖明[1] 班建东[1] 陈缨[1] 农君[1] 

机构地区：[1]广西医科大学蛇毒研究所,广西南宁530021 [2]广西医科大学基础医学院生物化学与分子生物学教研室,广西南宁530021

出　　处：《中国药理学通报》2018年第1期23-27,共5页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81360078;81460128)

摘　　要：目的探讨眼镜蛇毒神经生长因子NGF对肝纤维化关键细胞LX2的作用及机制。方法采用CCK-8法检测不同浓度NGF和LY294002对LX2细胞增殖的影响,流式法检测NGF对LX2细胞凋亡的影响,Western blot法研究NGF和LY294002单用与联用对p-Akt蛋白水平表达的影响。结果NGF可降低LX2细胞存活率,最小有效浓度为1 mg·L^(-1);增加LX2细胞凋亡率;降低p-Akt表达水平,而对Akt的表达水平无明显影响。结论 NGF可通过抑制PI3K/Akt信号通路的激活,促进LX2细胞凋亡,并有一定的浓度依赖性。本研究对阐明肝纤维化的发病机制,为临床上治疗肝纤维化均有重要意义。Aim To study the effect of cobra venom nerve growth factor( NGF) on inducing the apoptosis of LX2 cells,the key cells of hepatic fibrosis,through Akt signaling pathway and its underlying mechanism.Methods CCK-8 method was used to detect the proliferation of LX2 cells at different concentrations of NGF and LY294002. Flow cytometry was applied to detect the effect of NGF on the apoptosis of LX2 cells.Western blot was used to study the effects of NGF and LY294002 respectively,and their combination on the p-Akt protein level. Results NGF could decrease the survival rate of LX2 cells,and the minimum effective concentration was 1 mg·L^(-1); it increased the apoptosis rate of LX2 cells within the rise of concentration under a certain of range and decreased the expression lev-el of p-Akt,but it had no significant effect on the expression of Akt. Conclusions NGF may promote the apoptosis of LX2 cells by inhibiting the activation of PI3 K/Akt signaling pathway in a concentration-dependent manner. The study of the pathogenesis of liver fibrosis is significant for the clinical treatment of liver fibrosis.

关 键 词：肝纤维化 人肝星状细胞 眼镜蛇毒 神经生长因子 凋亡 PI3K/AKT 

分 类 号：R322.47[医药卫生—人体解剖和组织胚胎学] R329.25[医药卫生—基础医学]