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補(bǔ)體旁路激活致內(nèi)皮細(xì)胞纖溶凝血功能的改變及干預(yù)研究

發(fā)布時(shí)間:2018-05-25 05:33

  本文選題:補(bǔ)體 + 內(nèi)皮細(xì)胞; 參考:《中國(guó)藥理學(xué)通報(bào)》2017年10期


【摘要】:目的研究補(bǔ)體旁路激活導(dǎo)致的微血管內(nèi)皮細(xì)胞纖溶凝血功能的變化以及吡咯烷二硫氨基甲酸(PDTC)和白藜蘆醇(Res)的干預(yù)作用。方法采用眼鏡蛇毒因子激活血清補(bǔ)體旁路途徑。將補(bǔ)體旁路活化的血清作用于人微血管內(nèi)皮細(xì)胞(HMEC),檢測(cè)多個(gè)時(shí)間點(diǎn)細(xì)胞培養(yǎng)上清的水解發(fā)色底物活性變化和對(duì)凝血酶原時(shí)間(PT)、活化部分凝血活酶時(shí)間(APTT)的影響,并制備細(xì)胞懸液,檢測(cè)細(xì)胞表面的抗凝血功能變化情況。采用PDTC、Res對(duì)上述變化指標(biāo)進(jìn)行干預(yù)研究。結(jié)果 HMEC經(jīng)補(bǔ)體旁路活化產(chǎn)物刺激后,細(xì)胞培養(yǎng)上清的發(fā)色底物酶解活性明顯上調(diào);細(xì)胞培養(yǎng)上清導(dǎo)致正常血漿的APTT明顯縮短,同時(shí),對(duì)PT也有縮短的作用;經(jīng)補(bǔ)體旁路活化產(chǎn)物刺激HMEC后制備的各時(shí)間點(diǎn)細(xì)胞懸液對(duì)正常血漿的APTT有明顯的縮短作用,6 h刺激組的細(xì)胞懸液也表現(xiàn)出縮短PT的作用。PDTC和Res未能抑制發(fā)色水解活性的上調(diào),但Res對(duì)APTT的縮短有明顯的干預(yù)作用,而PDTC能在一定程度上抑制PT的縮短。結(jié)論補(bǔ)體旁路活化產(chǎn)物會(huì)導(dǎo)致HMEC纖溶凝血功能的失調(diào),而PDTC和Res有一定的干預(yù)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.
【作者單位】: 貴州省人民醫(yī)院干醫(yī)科;貴州省中國(guó)科學(xué)院天然產(chǎn)物化學(xué)重點(diǎn)實(shí)驗(yàn)室藥理與生物活性研究中心;貴州醫(yī)科大學(xué)省部共建藥用植物功效與利用國(guó)家重點(diǎn)實(shí)驗(yàn)室;
【基金】:國(guó)家自然科學(xué)基金資助項(xiàng)目(No 81260494) 貴州省高層次創(chuàng)新型人才項(xiàng)目(黔科合人才[2016]4018號(hào)) 貴州省科技創(chuàng)新人才團(tuán)隊(duì)項(xiàng)目(黔科合平臺(tái)人才[2016]5625號(hào))
【分類(lèi)號(hào)】:R392

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