西咪替丁对坏死性小肠结肠炎小鼠炎症免疫反应、肠道微生物的影响

摘要 目的：探讨与分析西咪替丁对坏死性小肠结肠炎（NEC）小鼠炎症免疫反应、肠道微生物的影响。方法：将建模成功的坏死性小肠结肠炎小鼠36只随机平分为三组-模型组、西咪替丁1组、西咪替丁2组，每组12只，每组每日分别灌胃生理盐水0.1mL、胃西咪替丁0.1 mL、胃西咪替丁0.2 mL，持续应用14 d，观察小鼠炎症免疫反应、肠道微生物变化情况。结果：西咪替丁1组、西咪替丁2组治疗第7 d、第14 d的体重都显著高于模型组（P<0.05），西咪替丁2组与西咪替丁1组对比有显著提高（P<0.05）。西咪替丁1组、西咪替丁2组治疗第14 d的肠组织白介素-2含量低于模型组（P<0.05），白介素-10含量高于模型组（P<0.05），西咪替丁2组与西咪替丁1组对比有显著差异（P<0.05）。西咪替丁1组、西咪替丁2组治疗第14 d的粪便双歧杆菌、乳酸杆菌相对表达水平显著高于模型组（P<0.05），大肠埃希菌相对表达水平显著低于模型组（P<0.05），西咪替丁2组与西咪替丁1组对比有显著差异（P<0.05）。西咪替丁1组、西咪替丁2组治疗第14 d的肠组织CaMKIV、CREM蛋白相对表达水平都显著低于模型组（P<0.05），西咪替丁2组与西咪替丁1组对比也显著降低（P<0.05）。结论：西咪替丁在坏死性小肠结肠炎小鼠的应用能调节炎症免疫反应平衡，促进小鼠体重恢复正常，还可降低肠组织CaMKIV、CREM蛋白相对表达水平，从而改善小鼠肠道微生物状况，且具有剂量依赖性。

Effects of Cimetidine on Inflammatory Immune Response and Intestinal Microorganism in Mice with Necrotizing Enterocolitis

ABSTRACT Objective: To investigate and analysis the effects of cimetidine on inflammatory immune response and intestinal microorganism in mice with necrotizing enterocolitis (NEC). Methods: 36 cases of mice with necrotizing enterocolitis were randomly divided into three groups: model group, cimetidine group 1, and cimetidine group 2, with 12 mice in each group. The model group, cimetidine group 1, and cimetidine group 2 were orally administrated with 0.1 mL of normal saline, 0.1 mL of gastric cimetidine, and 0.2 mL of gastric cimetidine daily. After continuous application for 14 days, the inflammatory immune response and intestinal microbial changes of the mice were observed. Results: The body weight of cimetidine group 1 and cimetidine group 2 on the 7th and 14th day of treatment were significantly higher than that of the model group(P<0.05), and the body weight of cimetidine group 2 were significantly higher than that of cimetidine group 1(P<0.05). At the 14th day of treatment, the content of IL-2 in intestinal tissue of cimetidine group 1 and cimetidine group 2 were lower than that of model group (P<0.05), and the content of IL-10 were higher than that of model group(P<0.05). There were significant difference compared between cimetidine group 2 and cimetidine group 1 (P<0.05). At the 14th day of treatment, the relative expression levels of Bifidobacterium and Lactobacillus in the feces of cimetidine 1 and 2 groups were significantly higher than those of the model group(P<0.05), while the relative expression levels of Escherichia coli were significantly lower than those of the model group (P<0.05). There were significant difference compared between cimetidine 2 and cimetidine 1 groups (P<0.05). The relative expression levels of CaMKIV and CREM proteins in the intestinal tissue of cimetidine 1 and 2 groups were significantly lower than those of the model group on the 14th day of treatment(P<0.05), and cimetidine 2 group also significantly decreased compared with cimetidine 1 group (P<0.05). Conclusion: The application of cimetidine in mice with necrotizing enterocolitis can regulate the balance of inflammatory immune response, promote the recovery of mice weight to normal, and also reduce the relative expression level of CaMKIV and CREM proteins in intestinal tissue, thus improving the intestinal microbial status of mice, which is dose dependent.