中医治法对胃癌前病变大鼠胃黏膜细胞凋亡的影响

Impact of three Chinese medicine therapies on gastric mucosal cell apoptosis in rats with gastric precancerous lesions

目的:在分子水平上探讨3种中医治法对胃癌前病变大鼠胃黏膜细胞凋亡的不同作用机制.方法:将60只Wistar大鼠随机分为正常对照组和造模组,采用以化学损伤为主的综合法复制大鼠胃癌前病变模型,确定造模成功后,将造模组大鼠随机分为模型对照组、健脾益气组、活血化瘀组和养阴荣络组,分别给予3组中药治疗6wk.光镜下观察大鼠胃黏膜组织学改变;采用TUNEL法检测大鼠细胞凋亡情况,计算凋亡指数(AI);采用免疫组织化学法检测大鼠胃黏膜细胞内凋亡相关蛋白(Bcl-2和Bax)的表达情况.结果:与正常对照组相比,模型组大鼠胃黏膜细胞的AI显著降低(均P<0.05),抑凋亡蛋白Bcl-2显著升高(均P<0.05),而促凋亡蛋白Bax显著降低(均P<0.05);与模型对照组相比,3用药组可显著升高胃癌前病变大鼠胃黏膜细胞中AI(18.93%±0.49%,25.93%±1.27%,14.83%±0.62%vs5.93%±1.02%,均P<0.05),降低Bcl-2的表达量,增加Bax的表达量(均P<0.05).结论:3种治法均能改善模型大鼠胃黏膜炎症,同时可诱导模型大鼠胃黏膜细胞发生凋亡,其作用以活血化瘀方最佳,相关蛋白Bcl-2、Bax可能是3种治法诱导细胞发生凋亡的重要调控因子.

AIM：To investigate the impact of three Chinese medicine therapies on gastric mucosal cell apoptosis in rats with gastric precancerous lesions and to explore potential mechanisms involved.METHODS：Sixty Wistar rats were randomly divided into normal control group and model control group.Gastric precancerous lesions were induced in rats by chemical injury to the stomach.The model control group was further divided into four subgroups：model control subgroup and three subgroups receiving different Chinese medicine therapies （by strengthening the spleen and replenishing Qi,promoting blood circulation and removing blood stasis,and nourishing Yin and dredging the channels and collaterals,,respectively）.The changes in gastric mucosa were observed under a light microscope.Apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling （TUNEL） assay to calculate apoptotic index （AI）.The expression of Bcl-2 and Bax proteins in gastric mucosa was detected by immunohistochemistry.RESULTS：Compared with the normal control group,the AI of gastric mucosal cells AI was significantly reduced （18.93%±0.49%,25.93%±1.27%,14.83%±0.62% vs 5.93%±1.02%,all P0.05）,the rate of gastric mucosal cells positive for Bcl-2 was significantly increased （all P0.05）,and the rate of gastric mucosal cells positive for Bax was significantly decreased （all P0.05） in the model control subgroup and the three treatment subgroups.Compared with the model control subgroup,the AI was significantly increased,the rate of gastric mucosal cells positive for Bcl-2 was significantly reduced,and the rate of gastric mucosal cells positive for Bax was significantly elevated in the three treatment subgroups （P0.05）.The most significant effect was noted in the subgroup treated by promoting blood circulation and removing blood stasis,followed by those treated by nourishing Yin and dredging the channels and collaterals,and strengthening the spleen and replenishing Qi.CONCLUSION：The three Chinese medicine therapies can improve gastric mucosal inflammation and induce apoptosis possibly by reducing Bcl-2 expression and increasing Bax expression.Therapy by promoting blood circulation and removing blood stasis has the most significant effect in promoting the apoptosis of gastric mucosal cells.