摘要
目的:研究氯吡格雷对大鼠急性胃黏膜损伤愈合的影响作用及其机制.方法:40只健康♂SD大鼠随机分为4组,每组10只:阴性对照组、单纯损伤组、10mg/kg氯吡格雷处理组、30mg/kg氯吡格雷处理组;以大剂量阿司匹林灌胃制造大鼠急性胃黏膜损伤模型后,对氯吡格雷处理组的大鼠以相应剂量的氯吡格雷进行灌胃处理,给药3d,每天1次.分别测定各组大鼠的胃黏膜损伤指数(lesionindex,LI);观察大鼠胃黏膜组织学变化;免疫组织化学法检测各组紧密连接蛋白Occludin的表达情况;免疫蛋白印迹法(Westernblot)检测紧密连接蛋白Occludin、ZO-1以及MAPK信号通路中磷酸化P38、磷酸化ERK及磷酸化JNK蛋白的表达量.结果:与损伤组相比,氯吡格雷处理组大鼠胃黏膜损伤加重,且30mg/kg组损伤重于10mg/kg组(39.8±5.05vs35.3±3.86,P<0.05);在阴性对照组、单纯损伤组、10mg/kg氯吡格雷处理组、30mg/kg氯吡格雷处理组中,大鼠胃黏膜中的紧密连接蛋白Occludin、ZO-1蛋白的表达逐渐下降,呈递减趋势(P=0.000),而磷酸化P38、磷酸化ERK蛋白表达则逐渐上升,呈递增趋势(P=0.000).结论:氯吡格雷能够抑制大鼠急性胃黏膜损伤的愈合,其可能是通过激活MAPK中的p38和ERK信号通路,下调胃黏膜上皮细胞间紧密连接蛋白Occludin和ZO-1的表达,破坏大鼠胃黏膜的屏障.
AIM： To determine the effect of clopidogrel on the healing of aspirin-induced gastric mucosal lesions in rats and to explore possible mechanisms involved. METHODS： Forty healthy male SD rats were randomly and equally divided into four groups： normal group, injury group, and two clopidogrel groups （10 mg/kg and 30 mg/kg）. Gastric mucosal lesions were induced in rats by oral administration of aspirin （200 mg/kg）. Rats of the clopidogrel groups were continuously administrated with clopidogrel for 3 days. After treatment, histological changes were evaluated under a microscope; the distribution of gastric epithelial tight junction protein occludin was determined by immunohistochemistry; and the expression levels of ZO-1, occludin, as well as phosphorylated ERK （p-ERK）, P38 （p-P38） and JNK （p-JNK） were determined by Western blot. RESULTS： Compared to the injury group, the lesion indices of the clopidogrel groups were significantly increased （39.8 ± 5.05 vs 35.3 ± 3.86, P 0.05）, and the increase was more significant in the high-does group than in the low-dose group （P0.05）. In clopidogrel groups, the expression levels of occludin and ZO-1 were lower in the clopidogrel groups than in the injury group （P0.05）, and in the high-does group than in the low-does group. Activation of P38 and ERK were more obvious in the clopidogrel groups than in the injury group （P0.05）. CONCLUSION： Clopidogrel significantly delays the healing of gastric lesions in rats probably by decreasing the expression of tight junction protein occludin and ZO-1 through the p38 and ERK signaling pathways.
出处
《世界华人消化杂志》
CAS
北大核心
2012年第10期861-865,共5页
World Chinese Journal of Digestology
基金
南京市医学科技发展专项基金资助项目
No.YKK10107~~
