瑞巴派特对阿司匹林所致人胃黏膜上皮细胞损伤的保护作用及其机制  

Protective effects and its mechanism of rebamipide on aspirin-induced injury in human gastric mucosal epithelium cells

作　　者：段兆涛[1] 张振玉[1] 吴海露[1] 袁芳岑[1] 姜宗丹[1] 何帮顺[2] 王书奎[2] 

机构地区：[1]南京医科大学附属南京医院,南京市第一医院消化科,210006 [2]南京医科大学中心实验室,210006

出　　处：《中华消化杂志》2014年第7期453-457,共5页Chinese Journal of Digestion

摘　　要：目的 探讨瑞巴派特对阿司匹林所致人胃黏膜上皮细胞GE91损伤的保护作用及其机制.方法 建立体外培养的GES1单层细胞模型,将细胞分为阴性对照组、阿司匹林损伤组、不同浓度（0.2、0.5、1.0 mmol/L）瑞巴派特联合阿司匹林组.检测各组细胞增殖情况、丙二醛含量和超氧化物歧化酶（SOD）活性.应用透射电子显微镜观察各组细胞内超微结构改变.采用Western印迹法检测各组细胞中核因子E2相关因子2（Nrf2）、血红素氧合酶1（HO-1）的蛋白表达.进行Nrf2干扰抑制试验,观察Nrf2小干扰RNA对HO-1蛋白表达的影响.多组间比较采用单因素方差分析,两组间比较采用t检验.结果 阿司匹林损伤组,0.2、0.5、1.0 mmol/L瑞巴派特联合阿司匹林组的细胞存活率分别为（49.56±3.88）％、（59.34±4.36）％、（70.79±5.96）％、（86.07±5.20）％,差异有统计学意义（F=30.634,P＜0.01）.与阿司匹林损伤组比较,0.2、0.5、1.0 mmol/L瑞巴派特联合阿司匹林组GE1细胞中丙二醛含量均显著降低[（2.26±0.25） nmol/mg比（1.85±0.13） rmol/mg比（1.62±0.11） nmol/mg比（1.13±0.15） nmol/mg],差异有统计学意义（F=23.821,P＜0.05）.与阿司匹林损伤组比较,0.5、1.0 mmol/L瑞巴派特联合阿司匹林组SOD活性升高[（8.49±0.89） U/mg比（11.50±1.03） U/mg比（13.74±0.76） U/mg],差异有统计学意义（F=25.666,P＜0.05）.透射电子显微镜下观察发现经阿司匹林处理后,细胞超微结构明显损伤,而瑞巴派特能减轻细胞损伤.0.2、0.5、1.0 mmol/L瑞巴派特联合阿司匹林组的Nrf2和HO-1蛋白相对表达量与阿司匹林损伤组比较（0.35±0.04比0.46±0.05比0.84±0.08比0.15±0.02,0.72±0.09比0.93±0.11比L.29±0.14比0.39±0.07）,差异均有统计学意义（F=92.550、38.235,P均＜0.05）.转染Nrf2小干扰RNA后,阿司匹林损伤组HO-1表达量为0.38±0.04,瑞巴派特联合阿司匹林组HO-1表达量为0.62±0.08,分别低于转染前的Objective To investigate the protective effects and its mechanism of rebamipide on aspirin-induced injury in human gastric mucosal epithelium cells （GES-1）.Methods GES-1 cells monolayer culture model was established in vitro.Then the cells were divided into negative control group,aspirin injured group and combination of rebamipide at different concentration （0.2,0.5,1.0 mrnol/L） and aspirin groups.The cell proliferation,the content of malondialdehyde （MDA） and the activity of superoxide dismutase （SOD） of each group were detected.The ultrastructural changes of each group were observed by transmission electron microscopy （TEM）.The expressions of nuclear factor erythroid 2-related factor 2 （Nrf2） and heme oxygenase-1 （HO-1） at protein level in the cells of each group were detected by Western blot.Nrf2 interfering suppression test was performed and then the influence of Nrf2 small interfering RNA （siRNA） on the expression of HO-1 protein was observed.One-way analysis of variance was performed for comparison among multi-groups and t-test was used for comparison between the two groups.Results The cell viability of aspirin injured group and combination of rebamipide at different concentration （0.2,0.5,1.0 mmol/L） and aspirin groups were （49.56±3.88）%,（59.34±4.36） %,（70.79 ± 5.96） % and （86.07 ± 5.20） %,respectively,and the difference was statistically significant （F=30.634,P〈 0.01）.Compared with aspirin injured group,the content of MDA significantly lowered in combination of rebamipide at different concentration （0.2,0.5,1.0 mmol/L） and aspirin groups （（2.26±0.25） nrnol/rng vs （1.85±0.13） nmol/mg vs （1.62±0.11） nmol/mg vs （1.13±0.15） nmol/mg）,and the difference was statistically significant （F=23.821,P〈0.05）.Compared with aspirin injured group,the activity of SOD significantly increased in combination of rebamipide at 0.5 and 1.0 mmol/L and aspirin groups （（8.49±0.89） U/rng vs （11.50±1.03） U/mg vs （13.74±0.76�

关 键 词：瑞巴派特 阿司匹林 核因子E2相关因子2 血红素氧合酶-1 氧化性应激 

分 类 号：R573[医药卫生—消化系统]