黄芪甲苷对氯吡格雷致大鼠胃黏膜损伤的治疗作用及机制

Therapeutic effect and mechanism of astragaloside IV on clopidogrel-induced gastric mucosal injury in rats

目的 探讨黄芪甲苷对氯吡格雷致大鼠胃黏膜损伤的治疗作用及机制。方法 将50只SD大鼠随机分为对照组、模型组及黄芪甲苷低、中、高剂量组,每组10只,分别予生理盐水1 mL/100 g、氯吡格雷15.6 mg/kg、氯吡格雷15.6 mg/kg+黄芪甲苷15、30、60 mg/kg灌胃,每日1次,干预1周后脱颈处死大鼠。用损伤指数评分评价胃黏膜损伤情况,用免疫组化SABC染色法检测胃黏膜组织中血管内皮细胞生长因子(VEGF)、磷酸化血管内皮细胞生长因子受体2(p-VEGFR2)蛋白表达。结果 与对照组比较,模型组胃黏膜损伤指数评分高,VEGF、p-VEGFR2蛋白表达低(P均<0.05);与模型组比较,各黄芪甲苷组胃黏膜损伤指数评分均低,VEGF、p-VEGFR2蛋白表达高(P均<0.05);黄芪甲苷低、中、高剂量组胃黏膜损伤指数评分逐渐降低,VEGF、p-VEGFR2蛋白表达逐渐升高(P均<0.05)。结论 黄芪甲苷可减轻氯吡格雷所致胃黏膜损伤,其作用机制可能与上调VEGF、p-VEGFR2表达有关。

Objective To investigate the therapeutic effect and mechanism of astragaloside IV on gastric mucosa injury induced by clopidogrel in rats. Methods Fifty sprague-dawley rats were randomly divided into the control group, model group, low-dose, medium-dose and high-dose astragaloside IV groups, with 10 in each group, which were given normal saline 1 mL/100g, clopidogrel 15. 6 mg/kg, clopidogrel 15. 6 mg/kg + astragaloside 15 mg/kg, clopidogrel 15. 6 mg/kg + astragaloside 30 mg/kg, clopidogrel 15. 6 mg/kg + astragaloside 60 mg/kg by gavage, once a day, and then rats were killed after 1 week of intervention. The gastric mucosa was evaluated by ulcer index, and the expression of vascular endothelial growth factor(VEGF) and phosphorylated vascular endothelial growth factor receptor 2(p-VEGFR2) in gastric mucosa was detected by immunohistochemical SABC staining. Results Compared with the control group, the model group had higher gastric mucosal injury index, and lower expression levels of VEGF and p-VEGFR2(all P<0. 05). Compared with the model group, all astragaloside IV groups had lower gastric mucosal injury index and higher expression levels of VEGF and p-VEGFR2(all P<0. 05). In the low-dose, medium-dose and high-dose astragaloside IV groups, gastric mucosal injury indexes decreased and the expression levels of VEGF and p-VEGFR2 increased gradually(all P<0. 05). Conclusions Astragaloside IV can alleviate the gastric mucosal injury induced by clopidogrel, and its mechanism may be related to up-regulated expression of VEGF and p-VEGFR2.