补体旁路过度激活影响体内凝血功能

Abnormality of blood coagulation induced by excessive activation of the alternative complement pathway

目的研究补体旁路的过度激活对体内纤溶、凝血及血小板的影响。方法采用尾静脉注射眼镜蛇毒因子(CVF)造成大鼠体内补体旁路的过度激活。检测大鼠给药前和给药后多个时间点血样的补体活性、t-PA、PAI-1、凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)、凝血酶时间(TT)、纤维蛋白原(FIB)、P-selectin、PF-4、β-TG、血小板数量及聚集活性的变化,并检测小鼠静脉给予CVF后其尾部出血时间的变化。结果大鼠注射CVF后,血清补体活性在1h内基本消失。t-PA和PAI-1含量在1h内有明显增加,在48 h时间点t-PA/PAI-1比值有明显下降(P<0.01);PT、APTT、TT均略有变化,而血浆FIB含量明显下降;补体旁路的过度激活导致血中P-selectin、PF-4、β-TG明显上调,血小板数量明显减少,凝血酶和花生四烯酸诱导的血小板聚集被明显抑制,而ADP诱导的血小板聚集只受到轻微影响。小鼠尾部出血时间在1 h时明显缩短。结论补体旁路的过度激活能明显影响体内凝血功能,导致血液的高凝状态。

Aim To investigate the effects of comple- ment activation of the alternative pathway on functions of fibrinolysis, coagulation, and platclet in rats. Methods Cobra venom factor （CVF） was injected into rats via tail vein. The blood samples collected at various time points before and after administration of CVF were assayed for complement activity, t-PA, PAI- l, PT, AFIT, Tr, FIB, P-selectin, PF-4, and β- TG. The platelet count in whole blood and platelet ag- gregation were also measured. After mice were injected CVF via tail vein, the tail bleeding time was deter- mined. Results The complement activity in rats was nearly exhausted in 1 h after administration of CVF. The levels of t-PA and PAI-1 were significantly up-reg- ulated at l h time point. The ratio of t-PA/PAI-1 de- creased significantly at 48 h time point （P〈0. 01）.PT, APTF, and TT slightly changed, whereas the con- centration of FIB significantly decreased. The concen- trations of P-selectin, PF-d and β-TG were significant- ly up-regulated in blood after administration of CVF. The platelet count in whole blood decreased significant- ly. The platelet aggregation induced by thrombin or AA was inhibited significantly, whereas ADP-induced ag- gregation was just slightly inhibited. Blooding time of mice was significantly shortened at l h time point. Conclusion Complement activation of the alternative pathway can induce abnormality of blood coagulation, which may cause hyper-coagulable state.