化痰消瘀方对胃癌前病变大鼠bcl-2、bax、mTOR及LKB1表达的影响

Effect of Huatan Xiaoyu prescription on expression of bcl-2,bax,mTOR and LKB1 in rats with gastric precancerous lesions

目的观察化痰消瘀方对胃癌前病变大鼠胃黏膜bcl-2、bax、mTOR、LKB1表达的影响。方法将100只大鼠随机分为正常组17只和造模组83只。正常组给予正常饮食,造模组采用N-甲基-N’-硝基-N-亚硝基胍(MNNG)联合饥饱失常法造模。将造模成功大鼠随机分为模型组、化痰消瘀低剂量组、化痰消瘀中剂量组、化痰消瘀高剂量组和维霉素组。正常组和模型组给予等量生理盐水灌胃,各给药组分别给予相应药物灌胃,1次/d,连续12周。37周末处死所有大鼠,取胃窦及胃体组织,镜下观察各组大鼠胃黏膜组织病理变化,计算胃癌前病变发生率;免疫组化法检测胃黏膜组织中bcl-2、bax、mTOR、LKB1蛋白表达情况。结果模型组胃癌前病变发生率为84.6%,各给药组胃癌前病变发生率均明显低于模型组(P均<0.05)。模型组大鼠bcl-2、mTOR蛋白表达水平明显高于正常组(P均<0.05),bax、LKB1蛋白表达水平明显低于正常组(P均<0.05)。各给药组bcl-2、mTOR蛋白表达水平明显低于模型组(P均<0.05),且化痰消瘀方中高剂量组明显低于维霉素组(P均<0.05);各给药组bax、LKB1蛋白表达水平明显高于模型组(P均<0.05),但化痰消瘀方低、中、高剂量组与维霉素组比较差异均无统计学意义(P均>0.05)。结论化痰消瘀方可逆转胃癌前病变的发生,作用机制可能与其能下调bcl-2、mTOR蛋白的表达,上调bax、LKB1蛋白的表达有关。

Objective It is to observe the effect of Huatan Xiaoyu prescription（HTXY） on the expression of bcl-2,bax,mTOR and LKB1 in rats with precancerous lesions of gastric cancer（PLGC）. Methods 100 rats were randomly divided into normal group（17 cases） and model group（83 cases）. Normal group was given normal diet,the model was built using the Nmethyl-N＇-nitro-N-nitrosoguanidine（MNNG） combined with Hunger and satiety method. The successful model rats were randomly divided into model group,low,middle and high dose HTXY group,and Vitacoenzyme group. The normal group and model group were given the same amount of normal saline,and each administration group were given the corresponding medicine for once a day,for a period of 12 weeks. At the end of 37 weeks,all rats were sacrificed and the gastric antrum and gastric tissue were taken,the pathological changes of gastric mucosa in rats were observed under microscope; the expression of bcl-2,bax,mTOR and LKB1 protein in gastric mucosa were detected by immunohistochemistry. Results The incidence rate of gastric precancerous lesions in model group was 84. 6%,the incidence rate of gastric precancerous lesions in each administration group was significantly lower than that in the model group（P〈0. 05）. The expression levels of bcl-2 and mTOR protein in model group were significantly higher than those in normal group（all P〈0. 05）,and the expression of bax and LKB1 protein were significantly lower than those in normal group（all P〈0. 05）. The expression of bcl-2 and mTOR protein in each administration group were significantly lower than those in model group（all P〈0. 05）,and the middle and high dose HTXY group were significantly lower than those of the Vitacoenzyme group（all P〈0. 05）; the expression of bax and LKB1 protein in each administration group were significantly higher than those in model group（all P〈0. 05）,but there was no significant difference among the low,middle and high dose HTXY group（all P〈0. 05）. Conclusion HTXY is effective in the treatment of rats with PLGC by down-regulation the expression of bcl-2,mTOR and up-regulation the expression of Bax and LKB1.