补体旁路激活致内皮细胞纤溶凝血功能的改变及干预研究

发布时间：2018-05-25 05:33

本文选题：补体 + 内皮细胞　；参考：《中国药理学通报》2017年10期

【摘要】：目的研究补体旁路激活导致的微血管内皮细胞纤溶凝血功能的变化以及吡咯烷二硫氨基甲酸(PDTC)和白藜芦醇(Res)的干预作用。方法采用眼镜蛇毒因子激活血清补体旁路途径。将补体旁路活化的血清作用于人微血管内皮细胞(HMEC),检测多个时间点细胞培养上清的水解发色底物活性变化和对凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)的影响,并制备细胞悬液,检测细胞表面的抗凝血功能变化情况。采用PDTC、Res对上述变化指标进行干预研究。结果 HMEC经补体旁路活化产物刺激后,细胞培养上清的发色底物酶解活性明显上调;细胞培养上清导致正常血浆的APTT明显缩短,同时,对PT也有缩短的作用;经补体旁路活化产物刺激HMEC后制备的各时间点细胞悬液对正常血浆的APTT有明显的缩短作用,6 h刺激组的细胞悬液也表现出缩短PT的作用。PDTC和Res未能抑制发色水解活性的上调,但Res对APTT的缩短有明显的干预作用,而PDTC能在一定程度上抑制PT的缩短。结论补体旁路活化产物会导致HMEC纤溶凝血功能的失调,而PDTC和Res有一定的干预作用。
[Abstract]:Aim to study the changes of fibrinolytic and coagulation function of microvascular endothelial cells induced by complement bypass activation and the intervention of pyrrolidine dithiocarbamate (PDTC) and resveratrol (resveratrol). Methods Cobra venom factor was used to activate the accessory pathway of serum complement. Human microvascular endothelial cells (HMECs) were treated with the serum activated by complement bypass pathway. The activity of hydrolyzed chromogenic substrate in supernatant of cell culture at different time points and the effects on prothrombin time (PTT) and activated partial thromboplastin time (APTT) were detected. Cell suspension was prepared to detect the changes of anticoagulant function on cell surface. PDTCnRes was used to intervene the above changes. Results the activity of chromogenic substrate of the supernatant of cell culture was upregulated obviously after stimulated by complement bypass activation product, and the supernatant of cell culture resulted in the shortening of APTT in normal plasma and the shortening of PT. The cell suspensions at different time points after stimulation of HMEC by complement bypass activation products had a significant shortening effect on APTT in normal plasma. The cell suspensions in the 6-hour stimulation group also showed the effect of shortening PT. PDTC and Res could not inhibit the up-regulation of chromophore hydrolysis activity. However, Res could significantly interfere with the shortening of APTT, and PDTC could inhibit the shortening of PT to some extent. Conclusion the activation products of complement bypass may lead to the disturbance of HMEC fibrinolytic coagulation function, while PDTC and Res have some intervention effects.
【作者单位】：贵州省人民医院干医科;贵州省中国科学院天然产物化学重点实验室药理与生物活性研究中心;贵州医科大学省部共建药用植物功效与利用国家重点实验室;
【基金】：国家自然科学基金资助项目(No 81260494) 贵州省高层次创新型人才项目(黔科合人才[2016]4018号) 贵州省科技创新人才团队项目(黔科合平台人才[2016]5625号)
【分类号】：R392

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