胃痞消抑制慢性萎缩性胃炎脾虚大鼠胃黏膜上皮细胞凋亡及调控蛋白Caspase-3和P_(53)表达

Inhibitory effect of Weipixiao on apoptosis,the expression of regulating protein Caspase-3 and P_(53) in gastric mucous epithelial cells in chronic atrophic gastritis rats with spleen deficiency

目的:探讨健脾化瘀解毒复方"胃痞消"阻断和逆转慢性萎缩性胃炎(CAG)癌前病变的分子机制。方法:采用致癌化合物N-甲基-N′-硝基-N-亚硝基胍(N-methyl-N′-nitro-N-nitrosoguanidine,MNNG)配合饥饱失常和耗气泻下法建立CAG脾虚模型。采用原位末端标记法检测胃黏膜上皮细胞凋亡阳性细胞数,用免疫组化法检测调控蛋白Caspase-3和P53表达阳性细胞数。结果:模型对照胃黏膜细胞凋亡阳性数及Caspase-3和P53的表达均较正常组明显增加(P<0.01);胃痞消3个剂量组(30,20,10 g.kg-1.d-1,qd,ig,给药4周)均能明显降低模型对照组出现的上述变化(P<0.01)。结论:健脾化瘀解毒复方胃痞消治疗CAG的作用机制可能与其下调胃黏膜上皮细胞凋亡调控蛋白Caspase-3和P53的表达,以及抑制黏膜上皮细胞凋亡有关。

Objective ： To explore the molecular mechanism of Weipixiao （ WPX）, a traditional Chinese medicine compound recipe, with the process method of invigorating the spleen and removing blood stasis and toxic substance（JPHYJD） ： It invigorates the spleen and remove blood stasis and toxic substance, on prevention and treating chronic atrophic gastritis（CAG） , to further intervene the occurring of gastric cancer. Methods： The model of CAG rats with syndrome of spleen deficiency was established by N-methyl-N＇-nitro-N-nitrosoguanidine（MNNG） and irregular fasting combined with purgative drugs; the influence of WPX on apoptosis, the expression of regulating proteins Caspase-3 and P53 in gastric mucous epithelial cells was observed using TdT-mediated dUTP-biotin nick end labeling（ TUNEL） technique and immunohistochemical stain, Results： The apoptosis, the expression of Caspase-3 and P53 in the cells of the model group were fortified than those of normal group（P 〈 0.01 ） ; but decreased in the three dose groups of WPX（P 〈0.01 ）. Conclusion ： The mechanism of JPHYJD-WPX may be related to down-regulating of the expression of regulating proteins Caspase-3 and P53, and thus decreasing the abnormal activity of apoptosis in the gastric mucous epithelial cells.