氯吡格雷对人胃黏膜上皮细胞损伤机制的研究  

The study on the mechanim of clopidogrel in human gastric epithelial GES-1 cell line injury

作　　者：姜宗丹[1] 张振玉[1] 汪志兵[1] 张弓羽[1] 何帮顺[1] 王书奎[1] 王劲松[2] 黄文斌[2] 

机构地区：[1]南京医科大学附属南京第一医院消化科,210006 [2]南京医科大学附属南京第一医院病理科,210006

出　　处：《中华消化杂志》2011年第11期724-728,共5页Chinese Journal of Digestion

基　　金：南京市医学科技发展专项基金（YKK10107）

摘　　要：目的探讨氯吡格雷对人胃黏膜上皮细胞（GES-1）的损伤机制。方法建立GES-1单层细胞模型，将细胞分为阴性对照组、U0126干预组、氯吡格雷干预组、联合干预组（U0126预处理后氯吡格雷干预），采用噻唑蓝（MTT）比色法和流式细胞术检测各组细胞增殖、凋亡情况；采用免疫细胞化学法检测各组P-ERK1／2的表达情况；采用Western印迹检测各细胞组p-ERK1／2蛋白的表达量。结果MTT结果显示与朋性对照组相比，U0126干预组、氯吡格雷干预组、联合干预组细胞增殖明显受到抑制，抑制率分别为21．8％±2．7％、46．3％±3．4％、82．9％±0．8％（F=615．556，P=0．000）；免疫细胞化学检测结果显示，U0126干预组、氯吡格雷干预组、联合干预组与阴性对照组相比p-ERK表达下降，分别为阴性对照组（10．80±1．64）分、（7．20±1．64）分、U0126干预组（4．40±0．89）分、联合干预组（1．40±0．55）分（F=49．426，P=0．000）。Western印迹检测结果与免疫细胞化学的趋势一致。结论在GES-1细胞模型中，氯吡格雷可能通过MAPK／ERK信号转导通路损伤GES-1细胞。Objective To explore the mechanism of clopidogrel in human gastric epithelial cell line （GES-1） injury.-Methods Set up GES-1 cells monolayer culture model. Then the GES-1 cells were divided into negative control group, U0126 intervented group, clopidogrel intervented group and combined intervented group （U0126 treated firstly then clopidogrel intervented）. The cell proliferation and apoptosis in each group was examined by methyl thiazolyl tetrazolium （MTT） assay and Flow cytometry. The expression of phosphorylated ERK1/2 in each group was detected by immunocytochemistry method, and the expression quantity of phosphorylated ERK1/2 in each group was measured by western blot. Results The result of MTT assay showed that compared with negative control group, the proliferation of GES-1 cells was inhibited in U0126 group, clopidogrel group and combined intervented group, and the inhibition percentage was 21.8 ± 2.7 %, 46.3 ±3.4 % and 82.9% ±0.8%respectively （F= 615. 556, P= 0. 000）. The result of immunocytochemistry indicated that the expression of p-ERK in U0126 group, Clopidogrel group and combined intervented group decreased compared with negative control group, which was 10.80±1.64, 7. 20±1.64, 4.40±0.89and 1.40 ± 0.55 respectively （F = 49. 426, P = 0. 000）. The result of western blot and immunoeytoehemistry was of the same trend. Conclusion In GES-1 cell model, clopidogrel may injure GES-1 cells through MAPK/ERK signal transduction pathway.

关 键 词：噻氯匹定 信号转导 胃黏膜 上皮细胞 细胞系 

分 类 号：R363[医药卫生—病理学]