酪酸梭菌预防小鼠幽门结扎型胃溃疡的机制研究

Preventive effects of Clostridium butyricum on gastric ulceration induced by pylorus ligature in mice

目的:建立小鼠幽门结扎型胃溃疡(gastric ulcer,GU)模型,观测酪酸梭菌(C.butyricum)对GU的预防作用并探讨其机制。方法:将40只ICR小鼠随机分为假手术组、模型组、奥美拉唑预防给药组和C.butyricum预防给药组。采用小鼠胃幽门结扎的方法建立GU模型,测量各组胃游离黏液量、胃液的p H、胃蛋白酶活性,并做常规HE染色观察胃组织的病理形态学变化,糖原(PAS)染色法观察胃组织糖原含量的变化,采用免疫组化检测胃黏膜组织中Bax、Bcl-2蛋白表达水平。结果:HE及PAS染色结果表明,C.butyricum预防能够显著减轻胃粘膜的损伤,其效果与奥美拉唑相当。与模型组相比,C.butyricum组胃液的p H显著升高(P<0.01);胃蛋白酶活性下降(P<0.05),但其效果不如奥美拉唑组(P<0.01);胃游离黏液量升高(P<0.01),糖原染色加深,与奥美拉唑组相比明显增多;Bax蛋白表达量降低(P<0.01)但Bcl-2蛋白表达水平显著上调(P<0.01)。结论:C.butyricum对小鼠幽门结扎型GU具有较好的预防作用,其机制可能与抑制胃酸分泌、胃蛋白酶活化,尤其是增加胃游离黏液的产生以及诱导bcl-2、抑制bax基因表达有关。

AIM： To investigate the preventive effects of Clostridium butyricum（ C. butyricum） on the type of pylorus ligated gastric ulcer（ GU） in mice and the underlying mechanisms. METHODS： ICR mice were randomly divided into 4 groups： sham operation group,model group,C. butyricum pretreatment group and omeprazole pretreatment group.Gastric pyloric ligation was adopted to establish GU model in mice. The gastric juice was collected to measure the content of gastric free mucus,the p H of gastric juice and the activity of pepsin. The gastric tissues were collected for routine HE staining to observe the pathological changes. The content of glycogen was detected by PAS staining. The protein expression of Bax and Bcl-2 in the gastric mucosa was also assessed by immunohistochemical staining. RESULTS： The HE and PAS staining showed that the C. butyricum pretreatment obviously attenuated the mucosa lesion induced by ligation. Compared with model group,the p H of gastric juice was significantly raised. The activity of pepsin fell off in C. butyricum group,which was lower than that in omeprazole group. In comparison with model group,the content of gastric free mucus was dramatically increased and PAS staining showed a significant rise in C. butyricum group,but not in omeprazole group. The protein expression of Bax was decreased and the protein expression of Bcl-2 was upgraded in C. butyricum group than those in model group. CONCLUSION： C. butyricum protects gastric mucosa against the challenge of pylorus ligation in mice and its mechanism may be related to inhibiting gastric acid secretion and the activation of pepsin,increasing the production of gastric free mucus,strengthening the expression of bcl-2 gene and inhibiting the expression of bax gene.