Edwards M H, Pierangeli S, Liu X, Barker J H, Anderson G, Harris E N
Department of Medicine, University of Louisville, Ky 40292, USA.
Circulation. 1997 Dec 16;96(12):4380-4. doi: 10.1161/01.cir.96.12.4380.
Previous studies have demonstrated that human monoclonal and polyclonal anticardiolipin antibodies have thrombogenic properties in vivo. Using such a model in which these antibodies have been shown to increase both the size of an induced thrombus and the duration of time in which such a clot lasts, we investigated whether hydroxychloroquine alters the dynamics of such thrombus formation.
Three groups of nine mice were injected with purified immunoglobulin G (IgG) from a patient with the antiphospholipid syndrome (IgG-APS) and then fed with hydroxychloroquine at various doses (100, 6, and 3 mg/kg body wt). Three control groups of mice were also studied, including mice injected with IgG-APS and then fed with placebo, as well as two other groups injected with IgG from normal human serum and fed either hydroxychloroquine or placebo. A standardized thrombogenic injury was subsequently induced in the femoral vein of each mouse and the area (size) of thrombus measured as well as the total period of time that thrombus was present. Mice treated with hydroxychloroquine and IgG-APS showed significantly smaller thrombi that persisted for a shorter period of time compared with animals treated with IgG-APS and placebo.
Hydroxychloroquine significantly diminished both thrombus size and total time of thrombus formation in mice previously injected with IgG-APS.
既往研究表明,人源单克隆和多克隆抗心磷脂抗体在体内具有致血栓形成特性。在这样一个模型中,已证实这些抗体会增加诱导血栓的大小以及此类血凝块持续的时间,我们研究了羟氯喹是否会改变此类血栓形成的动态过程。
将三组每组9只小鼠注射来自抗磷脂综合征患者的纯化免疫球蛋白G(IgG-APS),然后分别给予不同剂量(100、6和3mg/kg体重)的羟氯喹。还研究了三组对照小鼠,包括注射IgG-APS后给予安慰剂的小鼠,以及另外两组分别注射正常人血清IgG并给予羟氯喹或安慰剂的小鼠。随后在每只小鼠的股静脉诱导标准化的致血栓形成损伤,并测量血栓的面积(大小)以及血栓存在的总时间。与注射IgG-APS和安慰剂的动物相比,用羟氯喹和IgG-APS治疗的小鼠血栓明显更小,持续时间更短。
羟氯喹显著减小了先前注射IgG-APS的小鼠的血栓大小和血栓形成的总时间。