胃黏膜保护剂预防幽门螺杆菌培养上清液所致小鼠胃黏膜损伤

Preventive effects of gastric mucosal protective on H pylori CCS-induced gastric mucosal lesion in rats

目的:研究产毒幽门螺杆菌(Hpylori)的浓缩培养上清液(CCS)对小鼠胃黏膜的致病作用及胃黏膜保护剂硫糖铝和三九胃泰对CCS所致小鼠胃黏膜损伤的保护作用.方法:56只健康Balb/c小鼠随机分成7组:生理盐水组(Ⅰ组)、单纯损伤组(ⅡA组、ⅡB组)、硫糖铝保护组(ⅢA组、ⅢB组)、三九胃泰保护组(ⅣA组、ⅣB组),其中A组为小剂量毒素组,B组为大剂量毒素组.分别用硫糖铝和三九胃泰提前给小鼠灌胃,其后用不同剂量的产毒Hpylori菌株(NCTC11637)的CCS灌胃致急性胃黏膜损伤,然后在显微镜及电镜下观察胃黏膜组织学改变,分别测定各组胃黏膜损伤积分(EDS),以评价胃黏膜损伤程度及药物的预防保护效果.结果:产毒Hpylod的CCS可以对小鼠胃黏膜产生明显的损害,包括空泡变性、腺体排列紊乱以及糜烂、溃疡形成,但炎症反应不明显.在超微结构水平,Hpylori的CCS引起细胞间隙增宽、空泡变性、细胞质肿胀、线粒体及内质网扩张、微绒毛排列紊乱及脱落、吞噬溶酶体增多等改变.小剂量毒素引起的损害不如大剂量毒素引起的损害严重.Ⅰ,ⅡA,ⅡB,ⅢA,ⅢB,ⅣA,ⅣB各组的胃黏膜损伤积分依次为1.13±0.35,2.25±0.46,3.63±0.52,1.25±0.46,1.75±0.71,1.50±0.53,1.63±0.74:单纯损伤组(ⅡA,ⅡB)与生理盐水组(Ⅰ组)比较,胃黏膜损伤明显(P<0.01);硫糖铝保护组(ⅢA.ⅢB)、三九胃泰保护组(ⅣA,ⅣB)与单纯损伤组(ⅡA,ⅡB)比较,不论小剂量毒素组,还是大剂量毒素组,胃黏膜损伤程度均减轻,损伤积分均明显下降(P<0.05).结论:Hpylori的细胞毒素对鼠胃黏膜上皮细胞损害起重要作用,但并不引起明显的炎症反应;胃黏膜保护剂硫糖铝和三九胃泰对不同浓度Hpylori培养上清液所致的小鼠胃黏膜损伤有明显的预防和保护作用.

AIM: To determine the roles of H pylori concentrated culture supernatants (CCS) on the gastric mucosa of mouse and to investigate the protective effects of gastric mucosal protectives sucrafate and sanjiuweitai on CCS-induced gastric mucosal lesion in Balb/c rats. METHODS: Fifty-six healthy male Balb/c rats were randomly divided into seven groups: normal saline control (Ⅰ), injured simply (Ⅱ A, Ⅱ B), sucrafate pretreatment (Ⅱ A, Ⅱ B), sanjiuweitai pretreatment (Ⅱ A, Ⅱ B). Group A was dealt with small amounts of CCS and group B with large amounts of CCS. CCS were drawn from cytotoxic H pylori strain (NCTC11637). The four protective groups were pretreated with sucrafate and sanjiuweitai separately, and then infused orally with different amounts of CCS. The pathological changes on histological sections and ultra-structural sections of gastric mucosa were assessed under microscope or electron microscope. The epithelial damage scoring (EDS) of the gastric mucosa was measured. RESULTS: The management with large amounts of CCS from cytotoxic strains induced various epithelial lesions, which included vacuolation, erosions, ulcers and loss of gastric gland architecture. Infiltration of inflammatory cells in the lamina propria was not significant. At ultrastructural level, there was the presence of intracytoplasmic vacuoles, dilation of endoplasmic reticulum and mitochondrion, increasing of phagolysosomes, loose connection between cells and degenerative changes of microvilli. Small amounts of CCS from cytotoxic strain induced epithelial lesions less seriousey than large amounts of CCS. The results of the EDS of the gastric mucosa in the groups Ⅰ, Ⅱ A, Ⅱ B, Ⅲ A, Ⅲ B, Ⅳ A and Ⅳ B arranged successively as follows, 1.13±0.35, 2.25±0.46, 3.63±0.52, 1.25±0.46, 1.75±0.71, 1.50±0.53 and 1.63±0.74 respectively. A remarkable protection was found in gastric mucosa pretreated with sucrafate and sanjiuweitai. In comparison with the purely injured group, the EDS of the gastric mucosa descended significantly (P <0.05). CONCLUSION: Cytotoxin has an important role in the induction of gastric mucosa lesions, but not in eliciting obvious inflammation; The gastric mucosal protection of sucrafate and sanjiuweitai against CCS-induced gastric mucosal lesion in rats is significant.