幽门螺杆菌相关性消化性溃疡的细胞凋亡研究

目的：探讨幽门螺杆菌（Helicobacter pylori,HP)诱导胃上皮细胞凋亡的机制及细胞凋亡在HP相关性消化性溃疡（PU）中的作用。方法：内镜下胃粘膜活检取材，应用TUNEL法检测胃上皮细胞凋亡，免疫组化法检测凋亡调控蛋白bak、bcl-2的表达。结果：HP阳性胃溃疡（GU）和十二指肠（DU）患者细胞凋亡指数（AI）明显高于HP阴性非溃疡性消化不良（NUD）患者（P＜0．01）。根除HP后，AI在DU明显下降（P＜0．01），在GU无明显改变（P＞0．05）。HP阳性DU溃疡活动期AI明显高于愈合期和瘢痕期（P＜0．05），而HP阳性和GU溃疡三期AI无差异（P＞0．05）。bak蛋白表达在HP阳性PU明显高于HP阴性NUD患者（P＜0．05）。根除HP后，DU患者bak蛋白表达明显降低（P＜0．05）。GU患者虽有下降，但无统计学差异。bcl-2蛋白表达在HP阳性PU与HP阴性NUD之间无显著差异，HP根除前后亦无明显改变。结论：HP诱导胃上皮细胞凋亡在十二指肠溃疡发病中起重要的作用，HP诱导胃上皮细胞凋亡可能是通过bak路径实现的。

Studies on Gastric Epithelial Cell Apoptosis in HP Associated Peptic Ulcer

Purpose: To investigate the mechanism from helicobacter pylori(HP) that induced gastric epithelial cell apoptosis and the role of apoptosis in the development of peptic ulcer in HP infection. Methods: The density and distribution of the apopotic cells and the expression of bak and bcl 2 proteins were determined using terminal deoxynucleotidyl transferase mediated dUTP nick end labelling(TUNEL) and immunohistochemical approach in situ from biopsy specimens obtained by endoscopic examination. Results: The apoptotic index of HP associated gastroduodenal ulcer patients was much higher than that of HP negative non ulcer dyspepsia(NUD) patients(P<0.01). After eradication of HP, the apoptotic index of duodenal ulcer patients was distinctly decreasing(P<0.01), while there was no obvious change in gastric ulcer patients(P>0.05). In duodenal ulcer patients infected with HP, the patients with an active ulcer exhibited a significantly higher level of apoptosis than those with ulcers at both the healing and scarring stages(P<0.05), which was not found in three stages of gastric ulcer. The variations of bak protein expression was similar to that of apoptotic index(P<0.05). The expression of bcl 2 protein had no significant change between HP positive gastroduodenal ulcer patients and HP negative NUD patients. After eradication of HP, the expression of bcl 2 protein was also no obvious change in both duodenal ulcer patients and gastric ulcer patients(P>0.05). Conclusion: Gastric epithelial cell apoptosis induced by HP plays a crucial role in the development of duodenal ulcer and its realizition is by a bak dependent pathway.