莫沙必利对阿司匹林致大鼠急性胃黏膜损伤的保护作用

研究显示促胃肠动力药物莫沙必利对胃黏膜损伤具有一定的保护作用。目的：研究不同剂量莫沙必利对阿司匹林致大鼠急性胃黏膜损伤的保护作用及其机制。方法：将50只大鼠随机分为阴性对照组、单纯损伤组以及不同剂量莫沙必利干预组（0．25mg／kg、0．50mg／kg、0．75mg／kg）。干预组大鼠以不同剂量莫沙必利灌胃行预处理，以150mg／kg阿司匹林灌胃制备急性胃黏膜损伤模型。实验第4d，处死大鼠。评估大鼠胃黏膜损伤指数和组织学变化，以免疫组化法检测Occludin蛋白分布，蛋白质印迹法检测Occludin、ZO．1以及磷酸化ERK（p-ERK）、磷酸化JNK（p-JNK）和磷酸化p38（p-p38）蛋白表达。结果：与单纯损伤组相比，各莫沙必利干预组胃黏膜损伤指数均明显降低（P〈0．05）；胃黏膜组织学明显改善；胃黏膜Occludin、ZO-1蛋白表达呈剂量依赖性升高（P〈0．05）；胃黏膜p-ERK、p-p38蛋白表达呈剂量依赖性降低（P〈0．05）；而胃黏膜p-JNK蛋白表达无明显差异。结论：莫沙必利对阿司匹林致大鼠急性胃黏膜损伤具有明显保护作用，其机制可能为降低MAPKs信号通路中ERK和p38蛋白磷酸化程度，并上调胃黏膜紧密连接蛋白Occludin和ZO-1表达，从而改善胃黏膜屏障的功能。

Protective Effect of Mosapride on Acute Gastric Mucosal Lesions Induced by Aspirin in Rats

It is reported that mosapride, a gastrointestinal prokinetic drug, has a protective effect on gastric mucosal injury. Aims： To investigate the protective effect and mechanism of different doses of mosapride on acute gastric mucosal lesions induced by aspirin in rats. Methods： Fifty rats were randomly divided into five groups： negative control group, injury group, different doses of mosapride （0.25 mg/kg, 0.50 mg/kg and 0.75 mg/kg） protective groups. Rats in protective groups were pretreated with different doses of mosapride before induction of acute gastric mucosal lesions. Acute gastric mucosal lesions were induced by oral administration of aspirin （ 150 mg/kg）. All the rats were sacrificed on the 4th day. Gastric mucosal lesion index and histological changes were evaluated. Immunohistochemistry was used to detect the distribution of Occludin protein. The expressions of Occludin, ZO-1, phospho-ERK （p-ERK）, phospho-JNK （p-JNK） and phospho-p38 （p-p38） proteins were determined by Western blotting. Results： Compared with injury group, gastric mucosal lesion index in mosapride protective groups was significantly decreased; histological changes were ameliorated, and expressions of Occludin and ZO-1 proteins were significantly increased in dose-dependent manners （ P 〈 0.05 ） , and expressions of p-ERK, p-p38 proteins were significantly decreased in dose-dependent manners （ P 〈 0.05 ） ; no significant difference in expression of p-JNK protein was found. Conclusions： Mosapride has a protective effect on acute gastric mucosal lesions induced by aspirin in rats, probably via decreasing phosphorylation of ERK and p38 proteins in MAPKs signaling pathway, and increasing expressions of gastric mucosal tight junction protein Occludin and ZO-1, thus improving gastric mucosal barrier function.