幽门螺杆菌相关性胃炎胃粘膜上皮细胞的增殖凋亡及凋亡相关基因Fas的研究

Gastric epithelial cell proliferation,apoptosis and Fas gene in children with Helicobacter pylori associated chronic gastritis

目的 研究幽门螺杆菌 (HP)感染儿童胃粘膜上皮细胞的增殖、凋亡及凋亡相关基因Fas的变化 ,对幽门螺杆菌的致病机制进行探讨。方法 采用免疫组织化学和Tunel法检测 17例HP阳性小儿慢性胃炎和 19例HP阴性的小儿慢性胃炎胃粘膜上皮细胞增殖、凋亡和凋亡相关基因Fas的变化。结果 HP阳性组的胃粘膜上皮细胞增殖指数为 (9 0 2± 3 82 ) % ,凋亡指数为 (8 46±1 82 ) % ,Fas指数为 (31 2 9± 12 ) % ,HP阴性组胃粘膜上皮细胞增殖指数为 (3 41± 1 33) % ,凋亡指数为 (2 73± 0 85 ) % ,Fas指数为 (11 6 8± 9) %。三者在HP阳性组与HP阴性组之间差异有显著意义 ,与年龄性别无关 ;胃粘膜上皮细胞增殖指数在轻度胃炎为 (3 94± 3 5 1) % ,中度胃炎为 (6 5 3± 4) % ,重度胃炎为 (13 6 5± 7) % ,三者间差异有显著意义 ;凋亡指数在轻度胃炎为 (3 0 8± 1 0 5 ) % ,中度胃炎为 (5 82± 3) % ,重度胃炎为 (17 81± 2 6 3) % ,三者间亦差异有显著意义。细胞的增殖和凋亡在炎症程度间差异有显著意义。结论 HP促进胃粘膜上皮细胞的增殖和凋亡 ;Fas的表达在HP阳性组明显增加 ,提示Fas的过度表达可能是小儿HP相关性胃炎胃上皮细胞凋亡增加的原因之一。

Objective Helicobacter pylori is recognized as an important cause of chronic gastritis, however, little has been known about the role of Helicobacter pylori in pathogenesis of the disease. Maintenance of gastric mucosal integrity depends on the balance between cell loss due to apoptosis and cell proliferation. The aim of this study was to investigate wether Helicobacter pylori infection has any effects on the epithelial cell proliferation,apoptosis and Fas gene associated apoptosis,as well as its role in the pathogenesis of chronic gastritis. Methods Thirty-six (18 boys , 18 girls; age range 2.5～11 years, median 8.6)chronic gastritis children were studied. All the children underwent upper digestive tract endoscopy and biopsy specimens were taken. Helicobacter pylori infection was determined with microscopic examination with Gimsa staining and the rapid urease test. (17 Helicobacter pylori _positive, 19 Helicobacter pylori-negative). The severity of chronic gastritis was classified pathologically (22 had mild, 12 moderate and 2 had severe gastritis). We correlated the findings with cell proliferation studied by Ki67 immunostaining; the status of gastric apoptosis was tested by DNA fragmentation in situ using TdT-mediated dUTP biotin nick end labeling (TUNEL). Immunohistochemical method was used to detect the status of gastric Fas gene associated apoptosis. Results (1) Ki-67 labeling index (LI), apoptosis index in children with Helicobacter pylori positive gastritis were much higher than those of Helicobacter pylori negative gastritis patients [(9.02±3.82)% vs. (3.41±1.33)%; (8.46±1.82)% vs. (2.73±0.85)%; P <0.05]. Helicobacter pylori-positive cases displayed significantly enhanced proliferation and apoptosis within the gastric epithelium as compared to those of the cases who were Helicobacter pylori negative; (2) The expression of Fas of Helicobacter pylori positive gastritis children was much higher than that of Helicobacter pylori negative cases [(31.29±11.88)% vs. (11.68±8.95)%; P <0.05]. Helicobacter pylori-positive cases showed significantly enhanced expression of Fas within the gastric epithelium; (3) There was no association in Ki-67 labeling index, apoptosis index and the expression of Fas of Helicobacter pylori_positive gastritis children between age and sex. (4) Ki-67 LI% in mild, moderate and severe chronic gastritis were (3.94±3.51)%,(6.53±4.18)%,(3.65±7.57)%, respectively,there were significant difference among them. Apoptosis index (AI)% in mild, moderate and severe chronic gastritis was (3.08±1.05)%,(5.82±3.12)%,(27.8±2.63)%, respectively,which were significantly different. Ki-67, LI% and AI% were positively correlated with the severity of gastritis. Conclusions (1) Helicobacter pylori infection may promote gastric epithelial proliferation and apoptosis in chronic gastritis; (2) The expression of Fas in Helicobacter pylori positive gastritis was much higher than that of Helicobacter pylori negative gastritis, which suggested that Fas gene may play a role in gastric epithelial apoptosis in Helicobacter pylori infection; (3) Gastric epithelial proliferation and apoptosis were positively correlated with the severity of gastritis.