木瓜蛋白酶体外对血小板聚集的抑制作用

中国临床药理学与治疗学 ›› 2009, Vol. 14 ›› Issue (8): 906-911.

木瓜蛋白酶体外对血小板聚集的抑制作用

费鲜明¹, 周永列¹, 祁金文², 吴建国¹, 邱莲女¹, 王珍妮¹

¹浙江省人民医院中心实验室, ²浙江省人民医院临床药理研究室, 杭州 310014, 浙江

收稿日期:2009-06-04 修回日期:2009-07-12 出版日期:2009-08-26 发布日期:2020-10-30
通讯作者: 周永列, 男, 本科, 主任医师, 硕导, 研究方向:实验血液学和抗肿瘤药物的基础研究。E-mail:lab zyl@126.com
基金资助:
浙江省医学重点学科基金资助项目(07-010)

In vitro inhibitory effects of papain on platelet aggregation

FEI Xian-ming¹, ZHOU Yong-lie¹, QI Jin-wen², WU Jian-guo¹, QIU Lian-nv¹, WANG Zhen-ni¹

¹Central Laboratory, Zhejiang Provincial People's Hospital, ²Research Office of Pharmacology, Zhejiang Provincial People's Hospital, Hangzhou 310014, Zhejiang, China

Received:2009-06-04 Revised:2009-07-12 Online:2009-08-26 Published:2020-10-30

摘要/Abstract

摘要： 目的: 以洗涤血小板为模型, 观察木瓜蛋白酶在体外对血小板聚集的抑制作用, 以探讨其抗血栓作用的可能机制。方法: 将不同剂量木瓜蛋白酶与洗涤血小板作用, 以血小板聚集分析仪检测ADP 、花生四烯酸(AA) 、胶原和凝血酶诱导的血小板最大聚集率, 以流式细胞仪检测活化血小板膜纤维蛋白原受体(FIB-R) 和 P-选择素表达水平, 以 SDS-PAGE 分析血小板肌动蛋白聚合体的变化。检测 ADP 诱导的原发性高血压(PH) 及急性心肌梗死(AMI) 患者血小板最大聚集率和 FIB-R表达水平。结果: 木瓜蛋白酶剂量依赖性地抑制血小板聚集, 降低血小板最大聚集水平, 血小板聚集水平与木瓜蛋白酶剂量呈负相关 (P<0.01)。木瓜蛋白酶剂量依赖性地抑制 ADP 诱导的血小板 FIB-R 表达, 降低 FIB-R 表达水平(P<0.01)。木瓜蛋白酶降低 ADP 诱导的血小板膜 P-选择素表达水平和抑制肌动蛋白聚合体增加(P<0.01)。木瓜蛋白酶抑制 PH 及 AMI 患者血小板聚集和FIB-R表达(P<0.01)。结论: 木瓜蛋白酶通过抑制活化血小板膜纤维蛋白原受体的表达, 并抑制肌动蛋白聚合以及释放反应从而剂量依赖性地抑制血小板的聚集反应, 有抗血栓形成作用。

关键词: 木瓜蛋白酶, 血小板聚集, 纤维蛋白原受体, P-选择素, 肌动蛋白聚合体

Abstract: AIM: To observe the in vitro inhibito-ry effects of papain on platelet aggregation by washed platelet model, and explore the possible antithrombotic mechanism of papain .METHODS: Human washed platelets were mixed with different doses of papain. The maximal ratio of platelet aggregation induced by 5-adenosine liphosphate-disodium salt (ADP) , arachi-donic acid (AA) , collagen and thrombin, respective-ly, was measured with platelet aggregation analyzer. The expressions of fibrinogen receptor(FIB-R) and p-selectin(CD62p) on external membrane of activated platelet were determinated with flow cytometry .The changes of factin cytoskeletal structure in activated platelet were analyzed by SDS-PAGE .Platelet rich plasma(PRP) of patients with primary hypertension (PH) or acute myocardiac infarction(AMI) was treated to determinate the levels of aggregation and FIB-R ex-pression.RESULTS: Papain significantly inhibited platelet aggregation in a dose-dependent manner and reduced the levels of platelet aggregation, there was re-markably negative correlation between platelet aggrega-tion level and papain dose(P<0.01) .Papain notably inhibited FIB-R expression and decreased the levels of FIB-R expression activated by ADP in a dose-depen-dent manner.Papain reduced P-selectin expression on external membrane and lessened f-actins of platelet triggered by ADP .Papain significantly inhibited the levels of aggregation and FIB-R expression of platelets activated by ADP in patients with PH and AMI(P<0.01) .CONCLUSION: Papain can inhibit the ex-pression of fibrinogen receptor on external membrane of activated platelet and polymerization or release reac-tion, so the thrombocytic aggregation are inhibited in a dose-dependent manner, and papain has the effect of anti-thrombogenesis.

Key words: papain, platelet aggregation, fibrinogen receptor, P-selectin, actin polymer

中图分类号:

R965.2

费鲜明, 周永列, 祁金文, 吴建国, 邱莲女, 王珍妮. 木瓜蛋白酶体外对血小板聚集的抑制作用[J]. 中国临床药理学与治疗学, 2009, 14(8): 906-911.

FEI Xian-ming, ZHOU Yong-lie, QI Jin-wen, WU Jian-guo, QIU Lian-nv, WANG Zhen-ni. In vitro inhibitory effects of papain on platelet aggregation[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2009, 14(8): 906-911.

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