Blood:诱导获得性FXIII-B缺乏可持续降低FXIII-A

2020-08-03 MedSci原创 MedSci原创

单次注射后,靶向FXIII-B的siRNA可降低血浆FXIII-A的浓度超过3周;通过FXIII-B药理耗竭FXIII-A可以增强纤维蛋白溶解作用,且不会引起过多的出血。

凝血因子XIII(FXIII-A2B2)的活化形式FXIII-A*是一种止血酶,通过不可逆地交联纤维蛋白和抗纤溶蛋白来抑制纤维蛋白溶解。虽然FXIII-A*很重要,但目前尚无调节FXIII-A*的方法。

鉴于在FXIII-B缺陷患者中观察到的现象:FXIII-A减少,但无严重出血,Strilchuk等推测,用合适的小干扰RNA(siRNA)靶向肝FXIII-B或可安全地减少FXIII-A。

经实验验证,Strilchuk等证实用siRNA敲除小鼠和兔子的FXIII-B可导致FXIII-A持续且受控制地降低。单次注射后,血浆FXIII-A浓度减少90%可持续数周,重复注射可持续超过5个月,但血小板中的FXIII-A浓度不变。

在体外,α2-抗纤溶酶和纤维蛋白的交联受损,纤溶作用增强。在体内,颈动脉血栓闭塞后再灌注也得到增强。激发后再出血事件增加,但失血并未明显增加多。

综上所述,该方法模拟先天性FXIII-B缺乏症,提供了调节FXIII-A2B2活性的潜在药理和实验方法。

原始出处:

Amy W Strilchuk,et al. Sustained Depletion of FXIII-A by Inducing Acquired FXIII-B Deficiency. Blood. July 27,2020.

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    2021-03-24 smartjoy
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    2021-02-12 juliusluan78
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