三七总皂苷基于花生四烯酸代谢通路保护胃黏膜和增强阿司匹林抗血小板作用的实验研究  

Experimental Research on the Protective Effect of Panax Notoginseng Saponins on the Gastric Mucosa and the Anti-platelet Effect of Aspirin Based on Arachidonic Acid Metabolic Pathway

作　　者：王文婷[1,2] 薛梅 杨琳 宋磊 李长坤 杨斌 缪宇 马燕 史大卓 WANG Wenting;XUE Mei;YANG Lin;SONG Lei;LI Changkun;YANG Bin;MIAO Yu;MA Yan;SHI Dazhuo(Xiyuan Hospital,China Academy of Chinese Medical Sciences,Beijing 100091,China;China Academy of Chinese Medical Sciences,Beijing 100091,China))

机构地区：[1]北京中医药大学,北京100029 [2]中国中西医科学院西苑医院,北京100091 [3]岛津企业管理(中国)有限公司北京分析中心 [4]维也纳医科大学附属维也纳总医院

出　　处：《中西医结合心脑血管病杂志》2019年第9期1315-1320,共6页Chinese Journal of Integrative Medicine on Cardio-Cerebrovascular Disease

基　　金：国家自然科学基金项目(No.81273933;81102722);中国中医科学院中医药"一带一路"合作专项(No.GH2017-03-05)

摘　　要：目的观察三七总皂苷(PNS)保护急性心肌梗死(AMI)大鼠胃黏膜和增强阿司匹林(ASA)抗血小板的作用,并基于花生四烯酸(AA)代谢通路探讨其机制。方法结扎左冠状动脉前降支建立Wistar大鼠AMI模型,随机分为AMI模型组(model组)、ASA组、PNS组、PNS+ASA组,同时设假手术组(sham组),每组10只。造模后第2天各给药组给予相应药物灌胃,model组和sham组给予等量生理盐水,每日1次。灌胃4周后,TTC染色计算心肌梗死面积,光比浊法测定血小板聚集率,扫描电镜观察胃黏膜超微结构,ELISA法检测血小板环氧化酶-1(COX-1)活性,western blot法检测血小板COX-1蛋白,液相色谱-质谱联用技术检测血清、血小板及胃黏膜AA通路脂质代谢物水平。结果 model组心肌梗死面积、血小板聚集率较sham组显著升高(P<0.01);ASA组、PNS组、PNS+ASA组心肌梗死面积、血小板聚集率较model组显著降低(P<0.01);与ASA组比较,PNS+ASA组心肌梗死面积、血小板聚集率进一步降低(P<0.01)。ASA组胃黏膜上皮细胞明显损伤,PNS+ASA组胃黏膜上皮细胞损伤较ASA组明显减轻。model组血小板COX-1活性及表达较sham组升高(P<0.01);ASA组、PNS组、PNS+ASA组COX-1活性及蛋白表达较model组降低(P<0.01),且PNS+ASA组较ASA组进一步降低(P<0.01)。与单用ASA相比,PNS联合ASA能进一步升高血清总表氧二十碳三烯酸(P<0.01),降低血小板血栓素B_2水平(P<0.01),升高胃黏膜前列腺素E_2及下游代谢物水平(P<0.01)。结论 PNS联合ASA能减轻ASA诱导的胃黏膜损伤,增强ASA抗血小板作用,机制与调控AA代谢通路有关。Objective To investigate the protective effect of Panax notoginseng saponins(PNS)on the gastric mucosa and the anti-platelet effect of aspirin(ASA)based on arachidonic acid(AA)metabolic pathway.Methods The AMI model of Wistar rat was established by the ligation of left anterior descending coronary artery.They were randomly divided into AMI model group(model group,n=10),ASA group(n=10),and PNS group(n=10),and PNS+ASA group(n=10).Ten rats in sham group underwent the same surgery except for ligation.After model establishment,rats in each drug group were administrated with PNS,ASA or both by gastrogavage.Rats in the model group and the sham group were given the same amount of normal saline once a day.After 4 weeks,the myocardial infarct area(MIA)was evaluated by triphenyl tetrazolium chloride(TTC)staining.The platelet aggregation rate(PAR)was determined by light turbidimetry.The ultrastructure of gastric mucosa was observed by scanning electron microscope.The activity of platelet cyclooxygenase-1(COX-1)was detected by enzyme-linked immunosorbent assay(ELISA).The platelet COX-1 was detected by western blot.The lipid metabolites in AA pathway from serum,platelet,and gastric mucosa were determined by liquid Chromatograph-Mass Spectrometer(LC-MS).Results MIA and PAR were increased in AMI group compared with those in sham group(P<0.01).MIA and PAR in the ASA group,PNS group,and PNS+ASA group were significantly lower than those in the model group(P<0.01).Compared with the ASA group,MIA and PAR were further decreased in the PNS+ASA group(P<0.01).Gastric mucosal epithelial cells in ASA group were significantly damaged,which were significantly less in PNS+ASA group than that in ASA group.The activity and protein expression of platelet COX-1 in the model group were higher than those in the sham group(P<0.01).The COX-1 activity and protein expression in the ASA group,PNS group and PNS+ASA group were lower than those in the model group(P<0.01),which were further reduced in PNS+ASA group compared with the ASA group(P<0.01).Compar

关 键 词：阿司匹林 三七总皂苷 血小板抑制 胃黏膜保护 血小板聚集率 环氧化酶-1 花生四烯酸 

分 类 号：R542.2[医药卫生—心血管疾病] R285.5[医药卫生—内科学]