盐酸小檗碱抗大鼠胃癌前病变及其作用机制

目的]探讨盐酸小檗碱对实验性大鼠胃癌前病变的影响及与细胞凋亡和P53、Bcl-2蛋白、mRNA表达水平的关系.方法]采用N-甲基-N-亚硝基胍饮水法建立大鼠胃癌前病变模型,用盐酸小檗碱预防和大、中、小3种剂量干预治疗,观察大鼠的一般情况,以光镜观察胃癌前病变的发生率,并运用末端DNA标记法检测凋亡率(AI),免疫组化法检测细胞中P53和Bcl-2蛋白表达,逆转录多聚酶链式反应检测P53和Bcl-2的mRNA水平.结果]经盐酸小檗碱干预大鼠,其癌前病变的发生率明显降低,与模型组比较P＜0.05,AI显著提高,3种剂量组与模型组比较均P＜0.05,并伴有Bcl-2、突变型P53基因蛋白表达水平降低,野生型P53基因mRNA水平升高,Bcl-2基因mRNA水平下调,其中以大剂量组尤为显著,与模型组比较P＜0.01.结论]盐酸小檗碱能预防和治疗实验性大鼠胃癌前病变,其机制与提高细胞凋亡率和调控基因表达有关.

Effect of berberine on gastric precancerous lesions in rats and its mechanism

Objective] To study the effect of berberine on apoptosis, mRNA and protein expression of P53 and Bcl-2 in gastric precancerous lesions (GPL) of rats.Methods] Rat model of GPL was induced with N-methyl-N-subnitroguanidine. Berberine was used to prevent GPL and high, medium, and low dosage of berberine to treat GPL. Precancerous pathological changes of gastric epithelial cells were observed by optic microscope and apoptosis index (AI) was studied by TUNEL. The expression of P53 and Bcl-2 was detected with the method of immunohistochemistry and the expression of their mRNA with RT-PCR. Results] Berberine decreased the incidence of precancerous lesions of rats (compared with model group, P <0.05), and enhance apoptosis index (between the three berberine treatment groups and the model group, P <0.05). Berberine decreased the expression of Bcl-2, mutation P53 protein and Bcl-2 mRNA while elevated the wtP53 mRNA. There was significant difference between high dosage of berberine group and model group ( P <0.01). Conclusion] Berberine could prevent and treat the gastric precancerous pathological changes in rats, the mechanism of which may be related to enhancing AI and regulating the expression of P53 and Bcl-2.