胃粘膜肠化中π类谷胱甘肽转移酶的表达及其与幽门螺杆菌感染的相关性

目的 探讨π类谷胱甘肽转移酶（GST－π）在胃癌发生过程中的表达,及在肠化阶段以GST－π为代表的人体对致癌物解毒系统与幽螺杆菌（Hp)致毒作用间的相互作用。方法 利用S－P法对219例胃粘膜活检标本进行GST－π单克隆抗体的检测;利用HID－ABpH2.5-PAS粘蛋白组织化学技术对171例肠化粘膜进行分型;利用HE及Hp-DNA PCR及ELISA方法对正常胃粘膜和肠化粘膜进行Hp的检测。对80例Hp阳性患者进行Hp根除治疗,停药3个月后进行Hp、GST－π的检测。结果 正常胃粘膜未见GST-π的表达,肠化粘膜GST－π阳性率为69．6％,胃癌GST－π阳性率为44．4％,高于正常胃粘膜（P＜0．01）,低于肠化粘膜（P＜0．05）。Hp阴性组GST－π阳性率高于Hp阳性组（P＜0．05）。Hp根除治疗后,根除组GST－π表达高于未根除组（P＜0．05）。正常胃粘膜→肠化粘膜→胃癌组织中GST－π表达由无→高→低,GST－π弱阳性或阴性的Ⅲ型肠化与胃癌关系密切;肠化粘膜中GST－π弱阳性或阴性表达又合并Hp感染者,胃癌发生的危险性增加。结论 在胃粘膜上皮肠化阶段Hp的致毒作用与GS－π解毒作用彼此相互拮抗。

Expression of pi glutathione S-transferase in intestinal metaplasia and its relationship with Helicobacter pylori infection

OBJECTIVE: To study the dynamic change of glutathione S- transferase pi (GST-pi) in normal gastric mucosa, gastric mucosa with intestinal metaplasia (IM) and gastric cancer and to investigate the relationship between human carcinogen detoxification system and the virulence of Helicobacter pylori(H.pylori) in the stage of IM. METHODS: Two hundred and nineteen biopsy specimens of gastric mucosa, including 30 cases with normal gastric mucosa, 171 cases with IM and 18 cases with gastric cancer, were examined. The expression of GST-pi was detected by S-P immunohistochemical method. High-iron diamine /alcian blue pH2.5/periodic acid -Schiff (HID-ABpH 2.5-PAS) method was used to classify IM. H.pylori infection was confirmed or excluded by hematoxylin-eosin (HE) staining, of H.pylori-DNA PCR and ELISA. The 80 cases with H.pylori infection were treated by bismuthate + amoxicillin + metronidazole for three months and then biopsy specimens were taken again from the original sites. RESULTS: The GST-pi expression rate was 69.6% in gastric mucosa with IM, significantly higher than that in gastric cancer (44.4%, P < 0.05) and that in normal gastric mucosa (0%, P <0.01). The GST-pi expression rate in IM II, IM III, and IM I decreased in sequence (83.3%, 71.1%, and 48.9%). The GST-pi expression rate in IM without H.pylori infection was 79.0%, significantly higher than that in IM with HP infection (64.2%, P <0.05). The positive rate of GST-pi expression in H.pylori eradicated group was 81.9%, significantly higher than that before H.pylori eradication (63.8%, P < 0.01). The GST-pi expression rate decreased from normal gastric mucous to IM and to gastric cancer, and from IM I -->II-->III too. CONCLUSION: IM III with low or no expression of GST-pi is a high-risk condition of gastric cancer. The risk of gastric cancer increases when low or no expression of GST-pi is combined with H.pylori infection. The carcinogen detoxification role of GST-pi and the virulence of H.pylori might interact each other in the stage of intestinal metaplasia, the precancerous condition of gastric cancer.