摘要
目的探讨瑞巴派特对阿司匹林联合氯吡格雷(双抗)引起的胃黏膜损伤的影响及机制。方法将30只雄性SD大鼠随机分为对照组、双抗损伤组和瑞巴派特保护组。双抗损伤组大鼠给予阿司匹林(10.41 mg·kg^(-1)·d^(-1))联合氯吡格雷(7.81 mg·kg^(-1)·d^(-1))灌胃,瑞巴派特保护组大鼠在每次行双抗灌胃前1 h用瑞巴派特100 mg·kg^(-1)·d^(-1))对大鼠进行灌胃预处理,对照组给予等量的生理盐水灌胃,连续14 d;实验第15天处死所有大鼠,评估胃黏膜大体及病理损伤情况,应用免疫组化法检测胃黏膜中VEGF的表达,应用Western blotting检测胃黏膜中EGF的表达,应用TUNEL法检测胃黏膜中细胞的凋亡。结果与对照组相比,双抗损伤组大鼠胃黏膜大体及病理损伤明显增加,胃黏膜中EGF、VEGF表达明显减少(P<0.05),胃黏膜细胞凋亡显著增加(P<0.05);与双抗损伤组相比,瑞巴派特保护组胃黏膜损伤明显减轻,胃黏膜中EGF、VEGF表达明显增加(P<0.05),胃黏膜细胞凋亡显著降低(P<0.05)。结论瑞巴派特对双抗引起的胃黏膜损伤有一定的保护作用,其机制可能通过增加胃黏膜中EGF、VEGF的表达、降低细胞凋亡而促进损伤黏膜的修复。
Objective To investigate the effect and possible mechanism of Rabamipide on gastric injury induced by Aspirin combined with Clopidogrel in rats. Methods Thirty male SD rats were randomized into three groups： control group, Aspirin combined with Clopidogrel injury group and Rabamipide pretreatment group. Rats of Aspirin combined with Clopidogrel injury group were gavaged with Aspirin （10.41 mg·kg^-1·d^-1） and Clopidogrel （7.81 mg·kg^-1·d^-1） once daily for a continuous period of 14 days. Rats of rabamipide pretreatment group were gavaged with Rabamipide 1 hour once daily before given the same administration with the injury group. After 14 days administration, all rats were executed, and gastric mueosal lesion and histological changes were evaluated. Immunohistochemistry was used to detect the distribution and expression of VEGF. The gastric epithelial cell apoptosis of the rats was tested by TUNEL assay. The expression of EGF were determined by Western blotting. Results Gastric mucosal lesions and histological changes in Aspirin combined with Clopidogrel injury group were significantly increased compared with control group, and gastric mucosal lesions and histological changes in Rabamipide pretreatment group were all significantly decreased compared with injury group （P 〈 0.05）. The expressions of EGF, VEGF in Aspirin combined with Clopidogrel injury group were all significantly reduced （P 〈 0. 05） and cell apoptosis was significantly increased compared with control group （P 〈 0.05 ） ; expressions of EGF, VEGF were significantly increased in Rabamipide pretreatment group and cell apoptosis was significantly reduced compared with injury group. Conclusion Rabamipide has a protecitve effect on gastric injury induced by Aspirin combined with Clopidogrel in rats, possibly through increasing the expressions of EGF, VEGF and inhibiting cell apoptosis, and thus collectively promotes the healing process of gastric injury.
出处
《胃肠病学和肝病学杂志》
CAS
2017年第12期1389-1394,共6页
Chinese Journal of Gastroenterology and Hepatology
基金
南京市医学科技发展项目(YKK13103)
