不同剂量纳美芬对大鼠应激性溃疡胃黏膜保护作用及其机制研究

A study on the protective effect of different doses of nalmefene on gastric mucosa of rats with stress ulcer and its mechanism

目的探讨不同剂量纳美芬(Nalmefene)对大鼠应激性溃疡胃黏膜保护作用及其可能机制。方法将大鼠随机分为正常对照组(C)、应激溃疡组(M)、纳美芬低、中、高剂量治疗组(分别标示为N1、N2、N3)。于给药后处死动物,测定大鼠胃液pH值和胃溃疡指数(Ulceration index,UI),光镜观察胃黏膜病理改变,酶联免疫法检测大鼠血清IL-1β、IL-10、SOD、MPO、TNF-α、MDA以及胃黏膜组织PGE2的水平。结果与C组比较,M组胃液pH降低(P<0.01)、UI和各炎性因子水平均升高(P<0.01);与M组比较,纳美芬各剂量治疗组大鼠胃液pH均升高(P<0.01),而UI降低(P<0.01),各炎性因子水平均降低(P<0.01),以中高剂量治疗组效果显著(P<0.01)。结论纳美芬对应激性溃疡胃黏膜有明确保护作用,最佳药物剂量约为0.10 mg kg^(-1),其作用机制可能与降低胃液酸度,调节体内炎性因子之间的动态平衡有关。

Objective To investigate the protective effects of different doses of Nalmefene hydrochloride injection on the gastric mucosa of rats with stress ulcerand its possible mechanism.Methods The rats were randomly divided into normal control group(C),stress ulcer group(M),low,medium and high doses of Nalmefenetreatment group(labeled as N1,N2 and N3,respectively).The rats were sacrificed after complete administration of drug,and the pH value of gastric juice and the Ulceration Index(UI)of rats were determined.The pathological changes of gastric mucosa were observed under light microscope.The levels of interleukin 1β(IL-1β),interleukin 10(IL-10),superoxide dismutase(S OD),myeloperoxidase(MPO),tumor necrosis factorα(TNF-α),malondialdehyde(MDA)and gastric mucosa PGE2 in serum of rats were detected by enzym-linked immunosorbent assay.Results Compared with group C,the pH value of gastric juice in group M was significantly decreased(P<0.01),the levels of UI and various inflammatory factors were significantly increased(P<0.01).Compared with the M group,the pH value of gastric juice in Nalmefene groups were significantly increased(P<0.01),while the UI was significantly decreased(P<0.01),and the levels of inflammatory factors were significantly decreased(P<0.01),and the effect was significant in the middle and high dose group(P<0.01).Conclusions Nalmefene has a clear protective effect on gastric mucosa of stress ulcer,and the optimal drug dose is about 0.10 mg kg-1.The mechanism of action may be related to reducing gastric acidity and regulating the dynamic balance of inflammatory factors in vivo.