GLP-1通过抑制肝L02细胞脂性凋亡的可能机制  

Glucagon-like peptide-1 suppresses palmitic acid induced L02 cell apoptosis through JNK pathway

作　　者：王珣 王明林 鲁新耀 张鹏 于红刚[2] 胡义奎[3] 

机构地区：[1]武汉市武昌医院消化内科,湖北省武汉市430063 [2]武汉大学人民医院消化内科,湖北省武汉市430060 [3]华中科技大学同济医学院附属普爱医院神经内科,湖北省武汉市430034

出　　处：《世界华人消化杂志》2015年第1期16-21,共6页World Chinese Journal of Digestology

基　　金：武汉市卫生局科研基金资助项目;No.WX1321~~

摘　　要：目的:探讨胰高血糖素样肽-1(glucagon-like peptide-1,GLP-1)对棕榈酸(palmitic acid,PA)诱导的肝L02细胞脂性凋亡的影响及可能机制.方法:不同浓度PA(0.125、0.250、0.500 mmol/L)分别干预肝L02细胞;使用Cell Counting Kit-8(C C K-8)试剂盒检测其在12、24和48 h时的细胞增殖活性;将肝L02细胞随机分为对照组(NC组)、PA干预组(PA组)、PA+SP600125组(PA S P组)及PA+G L P-1组(PA G L P组),运用末端脱氧核苷酸转移酶介导的d U T P缺口末端标记测定法(T U N E L法)检测细胞凋亡;免疫印迹(Western blot)法检测c-Jun氨基末端激酶(c-Jun N-terminal kinase,JNK)、c-Jun、p-JNK及p-c-Jun蛋白表达.结果:和对照组相比较,经PA处理的肝L02细胞增殖活性降低(P<0.05),而且呈剂量依懒性;0.5 mmol/L PA干预24 h后,肝L02细胞凋亡率增加28.4%±2.6%,Western blot结果显示:JNK、c-Jun磷酸化增多;加用SP 600125或GLP-1后,细胞凋亡率分别减少21.7%±2.9%和19.4%±2.7%,差异具有统计学意义(P<0.05),PAGLP组p-JNK与p-c-Jun蛋白表达有所下降,差异具有统计学意义(P<0.05).结论:PA可诱导肝L02细胞脂性凋亡;此过程可能和JNK通路相关;GLP-1可能是通过抑制JNK信号通路来抑制肝L02细胞的脂性凋亡.AIM： To investigate the potential effects of glucagon-like peptide-1 （GLP-1） on palmitic acid （PA） induced apoptosis of hepatic L02 cells and the underlying mechanism. METHODS： L02 cells were stimulated with different levels （0.125, 0.250 and 0.500 mmol/L） of PA for different durations （12, 24 and 48 h） in the presence or absence of GLP-1. Cell Counting Kit-8 （CCK-8） assay was used to analyze the inhibitory effects on growth of L02 cells, and terminal-deoxynucleoitidyl transferase mediated nick end labeling （TUNEL） assay was used to observe the apoptotic rate of the cells. The expression of c-Jun N-terminal kinase （JNK）, c-Jun, p-JNK and p-c-Jun proteins was detected by Western blot assay. RESULTS： The growth of the L02 cells was significantly inhibited by PA in vitro, and PA induced the expression of p-JNK and p-c-Jun. GLP-1 suppressed the activation of JNK and c-Jun induced by PA. CONCLUSION： PA can inhibit the proliferation of L02 cells and induce cell apoptosis. The JNK signaling pathway is probably involved in the mechanism of PA induced apoptosis.

关 键 词：非酒精性脂肪性肝炎 游离脂肪酸 L02细胞 C-JUN氨基末端激酶 凋亡 

分 类 号：R575.5[医药卫生—消化系统]