S期激酶相关蛋白2在幽门螺杆菌L型致胃癌中的作用

目的：研究S期激酶相关蛋白2（S-phase kinase associated protein 2,Skp2）在幽门螺杆菌L型（Helicobacter pylori L-form,Hp-L型）感染致胃癌中所起的作用。方法：将胃癌BGC-823细胞与Hp-L型以不同比例共培养,在倒置显微镜下观察细胞形态学变化,并应用原位杂交和免疫组化分别检测Skp2 mRNA和蛋白在胃癌BGC-823细胞中的表达情况。同时收集慢性萎缩性胃炎（CAG）、胃肠腺化生（GIM）、胃不典型增生（GED）、胃癌（GCa）标本各40例,以40例轻度慢性浅表性胃炎（CSG）作为对照。应用革兰染色和免疫组化检测Hp-L型在上述组织中的感染情况;并进一步检测Hp-L型阳性组织中Skp2 mRNA和蛋白的表达情况。结果：Hp-L型作用BGC-823细胞后,倒置显微镜观察到细胞分裂增多,出现明显的生长加速现象;原位杂交和免疫组化检测发现BGC-823细胞中Skp2 mRNA和蛋白表达阳性率随细菌浓度的增加和作用时间的延长而逐渐增加（P〈0.05）。Hp-L型阳性组织中的Skp2mRNA和蛋白的表达阳性率按CAG、GIM、GED、GCa的顺序逐渐增加,但仅GCa组与CSG组间的差异具有统计学意义（P〈0.05）。结论：Skp2在Hp-L型感染的胃癌前病变及胃癌中均明显升高,提示其在胃癌的发生及发展中起着重要作用。

The effect of Skp2 in gastric carcinoma induced by Helicobacter pylori L-form infection

OBJECTIVE:To investigate the effect of Skp2 in gastric carcinoma induced by Helicobacter pylori L-form(Hp-L) infection.METHODS:The BGC-823 cells were co-incubated with different amount of Hp-L, and the expressions of Skp2 mRNA and protein were detected by in situ hybridization(ISH) and immunohistochemistry (IHC).Forty cases each of chronic atrophic gastritis(CAG),gastric intestinal metaplasia(GIM),gastric epithelial dysplasia(GED) and gastric carcinoma(GCa) were collected,and 40 mild chronic superficial gastritis(CSG) were also collected as control group.Hp-L was examined in each group by Gram’s staining.The expressions of Skp2 mRNA and protein were also evaluated.RESULTS:By inversion microscope,infected BGC-823 cells showed increased division indicating growth acceleration.Expressions of Skp2 showed that the positive cells gradually increased,became more obvious with increasing concentration of Hp-L and the duration of treatment in a concentration-and-time-dependent manner.The positive rate of mRNA and protein of Skp2 in CAG,GIM,GED and GCa of the positive Hp-L groups were higher than the negative groups,but only the GCa group was significant(P<0.05).CONCLSION:Skp2 showed an obvious increase in gastric pre-cancerous lesions and gastric carcinoma induced by Hp-L infection,which indicated it may play an important role in the development of gastric carcinoma.