米索前列醇预防非甾体抗炎药引起的小鼠肠黏膜损伤

Preventive effect of misoprostol against nonsteroidal anti-inflammatory drug-induced enteropathy in mice

目的探讨米索前列醇对非甾体抗炎药(NSAID)肠黏膜损伤的预防性保护作用。方法双氯芬酸钠灌胃建立NSAID肠黏膜损伤模型。雄性BABL/c小鼠60只随机分组,分别标记为:正常对照组、模型组、(200、400、800μg/kg)米索前列醇组。连续6 d灌胃处理。于第4天下午,除正常组外,其他用5 mg/kg双氯芬酸(10 m L/kg)灌胃处理。第7天对小鼠进行处理:采用FITC标记的葡聚糖检测肠黏膜通透性,分别取小肠组织标本进行HE染色,反转录PCR检测肠黏膜葡萄糖调节蛋白78(GRP78)、C/EBP同源蛋白(CHOP)、肿瘤坏死因子α(TNF-α)mRNA的表达,Western blot法检测以上分子的蛋白表达。结果与正常组比较,模型组小肠黏膜损伤严重,黏膜通透性显著升高,小肠黏膜绒毛发生变性、坏死、脱落、炎细胞浸润。而不同浓度米索前列醇给药组的肠黏膜损伤有不同程度的减轻,通透性改善;小肠GRP78蛋白的表达及GRP78、TNF-α、CHOP mRNA的表达与模型组相比明显下调。结论米索前列醇对NSAID肠病的预防有一定的作用。

Objective To investigate the preventive effect of misoprostol against non-steroidal anti-inflammatory drug （NSAID）-induced intestinal injury in mice. Methods NSAID-induced intestinal injury model was established through diclofenac sodium. Sixty specific-pathogen-free （SPF） BABL/c male mice were randomly divided into the following five groups： normal, model and three misoprostol groups with different concentrations （200, 400, 800 μg/kg）. Misoprostol was given to aforementioned three misoprostol groups by gavage once a day for 6 days. In the fourth day afternoon, 5 mg/kg （10 mL/kg） diclofenac was fed to all mice by gavage except for normal group. On the seventh day, all mice were sacrificed and intestinal permeability was detected using FITC labeled dextran. The intestinal tissues were taken for detecting the mRNA and protein expressions of intestinal glucose regulated protein 78 （GRP78）, C/EBP homologous protein （CHOP） and tumor necrosis factor alpha （TNF-α） through HE staining, reverse transcription PCR and Western blotting, respectively. Results Compared with the normal group, intestinal mucosa in the model group was seriously damaged and intestinal permeability significantly increased. The intestinal mucosal villus degeneration, necrosis, shedding, and inflammatory cell infiltration occurred in the model group. Yet, intestinal mucosal injury in different misoprostol groups was less severe. Their intestinal mucosal permeability was improved. The expressions of GRP78 protein and TNF-α, CHOP mRNAs on intestine were significantly reduced compared with those of the model group. Conclusion Misoprostol has preventive effect against NSAID-induced intestinal diseases.