基于分子对接及体内试验浅析三七总皂苷联用阿司匹林抗血小板作用的影响  

Research on the Anti-platelet Effects of Panax notoginseng Saponins Combined with Aspirin Based on Molecular Docking and in vivo Experiments

作　　者：孙宗喜 王雨[1] 杨万青[1] 吴娅丽 胡少男 杜守颖[1] Sun Zongxi;Wang Yu;Yang Wanqing;Wu Yali;Hu Shaonan;Du Shouying(School of Chinese Materia Medica,Beijing University of Chinese Medicine,Beijing 100029,China;Instituent of Ethnic Medicine,Guangxi International Zhuang Medicine Hospital;Guangxi University of Chinese Medicine)

机构地区：[1]北京中医药大学中药学院,北京100029 [2]广西国际壮医医院民族药研究所 [3]广西中医药大学

出　　处：《中国药师》2020年第12期2317-2321,2394,共6页China Pharmacist

基　　金：中央高校基本科研业务费专项(编号:2017-JYB-XS-071)。

摘　　要：目的:考察三七总皂苷联用阿司匹林对抗血栓作用的影响,浅析两药协同抗血小板的优势疗效,为临床合理联合用药提供科学数据。方法:采用分子对接技术初步预测三七总皂苷对环氧化酶-1(COX-1)和COX-2活性的影响,并以健康大鼠和皮下注射盐酸肾上腺素联合冰水浴诱导急性血瘀模型大鼠为研究对象,分别以三七总皂苷(31.25 mg·kg-1)、阿司匹林(15.62 mg·kg-1)及这两种药物组合(三七总皂苷31.25 mg·kg-1+阿司匹林15.62 mg·kg-1)连续灌胃10 d,ELISA法检测血清中血栓素B2(TXB2)和6-酮-前列环素F1α(6-keto-PGF1α)水平。结果:分子对接结果显示三七总皂苷对COX-1和COX-2潜在调控能力较弱;体内试验结果显示,健康大鼠预防给药,阿司匹林可显著性下调TXB2、6-keto-PGF1α水平和TXB2/6-ketoPGF1α比值(P<0.05),联用三七总皂苷可进一步下调TXB2水平和TXB2/6-keto-PGF1α比值(P<0.05);急性血瘀大鼠治疗用药,阿司匹林可显著降低模型组中异常升高的TXB2水平和TXB2/6-keto-PGF1α比值(P<0.05),联用三七总皂苷呈进一步下调趋势(P<0.05),但是对6-keto-PGF1α水平影响并不显著(P>0.05)。结论:三七总皂苷对COX-1和COX-2潜在调控作用较小,两药联用协同抗血小板聚集作用可能与三七总皂苷抑制酯酶所介导的阿司匹林水解活性有关。Objective: To explore the anti-thrombotic effects of Panax notoginseng saponins( PNS) combined with aspirin,clarify the superior anti-platelet efficacy of the combination use compared to single use,and provide scientific basis for the rational combination use of the two drugs in clinic. Methods: The influence of PNS on the activities of cyclooxygenase-1( COX-1) and COX-2 was predicted by molecular docking simulation. Healthy rats and rats with acute blood stasis syndrome induced by subcutaneous injection of epinephrine hydrochloride combined with ice water bath were selected as the research subjects. They were treated with PNS( 31.25 mg·kg-1),aspirin( 15.62 mg·kg-1) or the combination of two drugs( 31.25 mg·kg-1+15.62 mg·kg-1) for 10 days,and the levels of TXB2 and 6-keto-PGF1α in serum were detected using an ELISA method. Results: PNS exhibited weak regulatory potential on COX-1 and COX-2 by molecular docking. In the preventive medication of healthy rats,aspirin could significantly down-regulate the levels of TXB2,6-keto-PGF1α and TXB2/6-keto-PGF1α in vivo( P<0.05),and serum TXB2 and TXB2/6-keto-PGF1α were further reduced after the combination use with PNS( P<0.05). In the treatment of rats with acute blood stasis,aspirin could also significantly downregulate the abnormally evaluated levels of TXB2,6-keto-PGF1α and TXB2/6-keto-PGF1α in the acute blood stasis rats( P< 0.05).Moreover,after aspirin was combined with PNS,the levels of TXB2 and TXB2/6-keto-PGF1α were further reduced( P<0.05),while6-keto-PGF1α level was insignificantly altered( P>0.05). Conclusion: PNS shows mild potential regulation on the enzyme activities of COX-1 and COX-2,and can cooperate with aspirin to inhibit platelet aggregation,which might be related to the inhibitory effect of PNS on the esterase-mediated hydrolysis of aspirin.

关 键 词：三七总皂苷 阿司匹林 分子对接 急性血瘀 药物相互作用 

分 类 号：R285.5[医药卫生—中药学]