幽门螺杆菌长期感染蒙古沙土鼠腺胃模型的建立与评价

目的 建立幽门螺杆菌(Hp)长期感染蒙古沙土鼠(简称沙鼠)腺胃的模型,并观察Hp长期感染引起的胃黏膜病理改变及其与致癌剂N-甲基-N'-硝基-N-亚硝基胍(MNNG)是否具有协同致损伤作用.方法 健康雄性沙鼠90只随机分为4组:对照组(22只)、Hp组(24只)、MNNG组(20只)、Hp+MNNG组(24只).采用国际标准菌株NCTC11637灌胃,建立Hp长期感染沙鼠腺胃模型.并在接种Hp 4周后在相应组给予MNNG灌胃.接种Hp后20周及40周时分两批处死动物Warthin-Starry银染判定Hp定植情况,HE染色观察沙鼠胃黏膜病理改变.结果 (1)成功建立了Hp长期感染沙鼠腺胃的动物模型.(2)沙鼠胃黏膜病理学变化显示:20周时,对照组沙鼠胃黏膜腺体排列整齐,未见腺体萎缩、肠上皮化生、非典型增生等异常表现;Hp组3只出现腺体萎缩;MNNG组1只出现腺体萎缩;Hp+MNNG组5只出现腺体萎缩,1只出现肠上皮化生.40周时,对照组胃黏膜病理未见异常表现;Hp组6只出现腺体萎缩,5只出现肠上皮化生,1只出现非典型增生;MNNG组5只出现腺体萎缩,2只出现肠上皮化生,无非典型增生发生;Hp+MNNG组10只全部出现腺体萎缩,7只出现肠上皮化生,5只出现非典型增生.Hp+MNNG组发生癌前病变的例数多于其他各组,由于时间尚短,暂未观察到胃癌发生.结论 Hp NCTC11637可以稳定的定植于沙鼠腺胃黏膜,并使之出现类似于人感染Hp后出现的各种病理变化;Hp与MNNG两者均可对胃黏膜造成损伤,两者同时作用会导致胃黏膜更严重的病理改变,两者存在协同致损伤作用.

Establishment of Mongolian gerbil model of long-term Helicobacter pylori infection

Objective To establish a model of long-term infection with Helicobacter pylori (Hp) in Mongolian gerbil (Meriones unguiculatus),and to investigate if Hp combined with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) has a synergistic effect to induce gastric mucosa injury.To investigate pathological changes of gastric mucosa during long-term Hp infection in Mongolian gerbil model.Methods 90 healthy male Mongolian gerbils were randomly divided into 4 groups:Hp group (n=24) undergoing gastric perfusion of Hp suspension of the line NCTC11637 in brain-heart infusion(BHI)108-109CFU/ml once a day for 10 days and then gastric perfusion of 1 ml normal saline (NS) once a day for 10 days since the 4th week after Hp perfusion.Hp+MNNG group (n=24) undergoing gastric perfusion of Hp solution once a day for 10 days and then MNNG l ml(2 ms/ml) once a day for 10 days,MNNG group (n=20) undergoing gastric perfusion of BHI once a day for 10 days and then gastric perfusion ofMNNC once a day for 10 day since the 4th week after BHI perfusion,and control group (n=22) undergoing gastric perfusion of BHI once a day for 10 days and then gastric perfusion of NS again once a day for 10 day since the 4th week after the BHI peffusion.4 and 8 weeks 1 gerbil from the control group and 2 gerbils from the Hp and Hp+MNNG groups each were killed to observe the pathological changes and Hp eolonization by liquid-based urease test and Warthin-Starry silver staining.20 and 40 weeks after the Hp inoculation 10 gerbils from each group were killed to observe the pathology of the gastric mucosa.Results (1) A Mongolian gerbil model of long-term Hp infection Was successfully established.(2)Hp induced the process progressing from normalgastric mucosa→chronic atrophic gastritis→intestinal memplasia→ dysplasia.Until 40 weeks after Hp infection,the gastric mucosa of the control group remained normal.Twenty weeks after Hp infection 3 gerbils in the Hp group and 1 gerbil in the Hp+MNNC group showed glandular atrophy and intestinal metaplasia respectively,and 40 weeks after infection,glandular atrophy,intestinal memplasia,and dysplasia at different degrees in the gastric mucosa were seen in the three experimental groups.The pathological changes of the Hp+MNNG group were the most severe.The incidence rates of precancerous lesions of the Hp+MNNG group were significantly higher than those of the other groups,but no gastric carcinoma was found in the experimental animals.Conclusion Hp colonizes stably in the glandular gastric mucosa of Mongolian gerbils.The histological changes after infection are similar to those of the Hp infected human being.Hp and MNNG botll cause the injury of gastric mucosa.With synergistic effect.the two pathogenic agents attack the gastric mucosa,they cause more severe injury.