十二指肠胃反流模型大鼠胃黏膜组织Cyclin D1、p16蛋白表达

The Expression of Cyclin D1 and p16 Gene Proteins in Gastric Mucosa in Duodenogastric Reflux Rats Model

目的:探讨十二指肠胃反流(DGR)引起大鼠胃黏膜损伤及癌变的发病机制。方法:健康成年雄性SD大鼠75只随机分为两组:①DGR模型组55只。根据手术造模方式及反流量大小分为全反流组与部分反流组。②假手术对照组20只。采用pH监测仪测定胃液pH,用酶法测定胃液胆汁酸(TBA),确定DGR模型成功。进行为期3个月和9个月胃黏膜损伤的动态观察。采用免疫组化方法(S-P)分析不同病变胃黏膜组织Cycli n D1、p16蛋白的表达。结果:DGR模型大鼠胃液pH及TBA明显升高(P<0.01),证明DGR模型成功。模型大鼠病理改变出现浅表性胃炎→萎缩性胃炎→异型增生的动态演变过程。萎缩性胃炎组及异型增生时Cyclin D1蛋白表达显著高于假手术对照组及浅表性胃炎组(P<0.05),癌基因Cyclin D1为高表达。在萎缩性胃炎与异型增生之间Cyclin D1表达差异无显著性(P>0.05)。而p16蛋白表达则相反,在假手术对照组最高,在异型增生组最低,两组之间差异有显著性(P<0.01),抑癌基因p16在异型增生时为低表达。Cyclin D1与p16表达呈负相关(r=-0.53)。结论:Cyclin D1、p16蛋白表达异常是DGR胃黏膜损伤及癌变的分子机制之一。

Objestive: To investigate the pathogenesis of gastric mucosa injury and cell canceration caused by duodenogastric reflux (DGR) . Methods: Adult male SD rats(75)were randomly divided into two groups, one was model rats with DGR(55) which was classified into full reflux group and part reflux group according to its degree of reflux. Another was sham operation rats(20)as control group. Rat models were confirmed to be successful induced by monitoring pH,measuring total bile acid (TBA)in gastric juice . After gastrojejunostomy operation for 3 months and 9 months, the pathological charactor of gastric mucosa in model rats was CSG, CAG and Dys by using light microscope. S-P immunohistochemical staining was used to detect the expression of Cyclin D1, p16 proteins, Results: The pH and TBA of gastric juice in model rats were significantly higher than those in control rats ( P < 0.01) . These results demonstrated that rat models with DGR was successful .The pathology of gastric mucosa in rat models represented CSG,CAG and Dys.The positive expression rates of Cyclin D1 in CAG and Dys were significantly higher than those in CSG and control group (P < 0.05) .There was no significantly difference between CAG and Dys ( P> 0.05) .In contrast, the positive expression rate of p16 in control group was significantly higher, compared with Dys group ( P < 0.01). Gyclin D1 and p16 were negatively correlated (r = -0.53). Conclusion: The abnormal expression of Cyclin D1 and p16 gene proteins may be one of major pathogeneses of gastric mucosa injury and cell canceration in DGR.