幽门螺杆菌感染Balb/c小鼠模型的建立及对N-甲基-N-亚硝基脲诱发胃癌的影响

Establishment of Helicobacter pylori infection model and influence of its infection on N-methyl-N-nitrosourea-induced gastric carcinogenesis in Balb/c mice

目的建立一种稳定的造模周期短的幽门螺杆菌(Hp)感染模型,观察Hp对小鼠胃黏膜的损害程度,同时研究Hp感染是否促进亚硝基类化合物的致癌作用。方法94只Balb/c小鼠分为4组。第1组单用N甲基N亚硝基脲(MNU);第2、3组小鼠用灌胃法定植Hp,第3组小鼠加用MNU灌胃;第4组为正常对照。36周后处死全部小鼠,分别用尿素酶、Giemsa染色和微需氧细菌培养检测Hp定植;H E染色进行鼠胃黏膜病理诊断。结果Balb/c小鼠Hp定植率达93.9%。Hp单一处理组中度以上炎症占100.0%,其中萎缩性胃炎占20.0%;而Hp和MNU联合处理组中度以上炎症占100.0%,其中萎缩性胃炎占23.1%,不典型增生占42.3%和57.7%(胃体和胃窦),并发现2只小鼠有低分化腺癌,占7.1%。Hp处理组和Hp+MNU联合处理组在炎症程度上与正常对照组相比,差异有统计学意义(P<0.01)。结论本实验成功建立了Hp感染小鼠模型,验证了Hp和胃癌的发生有高度相关性,证实Hp在协同MNU致癌性中的作用,提示胃癌的发生并非Hp感染单一因素的结果,而和多因素共同作用有关。

Objective To establish a new Helicobacter pylori(H.pylori) infection model which is more stable and to find the relationship between H. ~pylori infection and gastric carcinogenesis induced by nitrosourea. Methods A total of 94 Balb/c mice were divided into four groups. Two groups of mice were inoculated with H.pylori, among which one group of mice received continuous N-methyl-N-nitrosourea(MNU) administration via the drinking water. The third group were only given MNU, and the forth as control. After 36 weeks, all the mice were ~sacrificed . The infection of H.pylori in gastric mucosa of the mice was analyzed by rapid urease test, ~Giemsa staining and culture. The histopathological changes in the gastric mucosa of mice were assessed in ~H-E stained sections. Results The total infection rate of H.~pylori in Balb/c mice was 93.9%. All the mice in group with H.pylori infection alone had chronic gastritis, in which 20.0% was atrophic gastritis. In the group of mice with H.pylori infection and MNU intake, all had chronic gastritis, and among them 23.1% had atrophic gastritis, 42.3% corpus dysplasia and 57.7% antrum dysplasia. In this group, two mice (7.1%) with low differentiated adenocarcinoma were found. Compared with control group, two groups with H. ~pylori infection only and H. ~pylori plus MNU intake reached statistical difference in the view of inflammatory latitude (P<0.01). Conclusions We successfully established a H.pylori infection model of Balb/c mice and verified that there is a close relationship between H.pylori infection and gastric carcinogenesis. The initiation of gastric carcinoma is a result of multiple factors, rather than H. pylori alone. However, the H.pylori infection may play a major role in gastric carcinogenesis.