基于Survivin、Livin凋亡抑制蛋白探讨化痰消瘀方逆转胃癌癌前病变的作用机制

Expression of Survivin and Livin in precancerous lesions of gastric cancer in rats: Implications for therapeutic effects of Huatanxiaoyu decoction

目的:探讨化痰消瘀方通过凋亡抑制蛋白Survivin、Livin逆转胃癌癌前病变(precancerous lesions of gastric cancer,PLGC)的可能作用机制.方法:将6-8 wk SD♂大鼠96只,随机分为正常组与造模组,使用N-甲基-N'-硝基-亚硝基胍、雷尼替丁药物加饥饱失常的造模方法制备PLGC动物模型.将成功造模后的大鼠随机分为模型组、低剂量中药组、中剂量中药组、高剂量中药组及西药对照组,第28 wk处死并依次从胃体、胃窦处分别取材并保存.用HE染色以辨别大鼠胃黏膜病理改变,用免疫组织化学的方法对比凋亡抑制蛋白Survivin、Livin在各组大鼠胃黏膜组织中的表达情况.结果:(1)HE染色结果提示正常组胃黏膜未出现PLGC改变;模型组均出现PLGC改变;中药中、高剂量治疗组PLGC病理改善具有统计学意义(P<0.05)且高剂量组疗效优于其他各治疗组(P<0.05);叶酸片治疗组PLGC改善较模型组有统计学意义(P<0.05);(2)免疫组织化学结果显示Survivin、Livin蛋白在正常组极少表达;模型组表达较正常组显著增加(P<0.01);各中药治疗组蛋白表达均较模型组减少,且呈剂量依赖性(P<0.05),中药高剂量组蛋白表达较其他中药组及西药对照组明显减低(P<0.05).结论:结果提示化痰消瘀方可以逆转PLGC,其疗效优于单纯叶酸片治疗,且作用机制与抑制细胞凋亡抑制蛋白Survivin、Livin表达密切相关.

AIM： To explore whether Huatanxiaoyu decoction exerts therapeutic effects against precancerous lesions of gastric cancer（PLGC） by suppressing Survivin and Livin expression in rats. METHODS： Ninety-six 6-8-week-old male SD rats were randomly divided into either a normalgroup or a model group. N-methyl-N’-nitroN-nitrosoguanidine（MNNG）, ranitidine and irregular diet were used for preparing PLGC animal models. After successful modeling, the model rats were randomly divided into a model group, low-, medium- and high-dose Chinese medicine groups, and a western medicine（folie acid tablets） group. After 8 wk of treatment, gastric body and antrum mucosal specimens were taken for observing pathological changes of the gastric mucosa after HE staining, or for detecting the expression of Survivin and Livin by immunohistochemistry. R E S U LT S ： The normal group showed no PLGC changes, while all the other groups had PLGC changes. Medium- and high-dose Huatanxiaoyu decoction significantly improved PLGC changes（P 〈 0.05）, and the improvement was better in the high-dose group than in the other treatment groups（P 〈 0.05）. Treatment with folie acid tablets also significantly improved PLGC pathology compared with the model group（P 〈 0.05）. The expression of Survivin and Livin proteins in the model group was significantly higher than that in the normal group（P 〈 0.01）. Compared with the model group, Huatanxiaoyu decoction significantly decreased the Survivin and Livin expression in a dose-dependent manner（P 〈 0.05）, and the decrease was more significant in the high-dose group than in the other groups（P 〈 0.05）. CONCLUSION： Huatanxiaoyu decoction is superior to folie acid in treating PLGC, and the therapeutic effects may be closely related to the inhibition of Survivin and Livin expression.