Lactadherin能促进微粒的清除从而预防凝血障碍并提高创伤性脑损伤小鼠的生存率

文献 Lactadherin Promotes Microvesicle Clearance to Prevent Coagulopathy and Improves Survival of Severe TBI Mice 于 2017年 发表在 Blood 原文链接

Abstract

Coagulopathy is common in patients with traumatic brain injury (TBI) and predicts poor clinical outcomes. We have shown that brain-derived extracellular microvesicles, including extracellular mitochondria, play a key role in the development of TBI-induced coagulopathy. Here, we further show in mouse models that the apoptotic cell-scavenging factor lactadherin, given at a single dose of 400 μg/kg 30 minutes before (preconditioning) or 30 minutes after cerebral fluid percussion injury, prevented coagulopathy as defined by clotting time, fibrinolysis, intravascular fibrin deposition, and microvascular bleeding of the lungs. Lactadherin also reduced cerebral edema, improved neurological function, and increased survival. It achieved these protective effects by enhancing the clearance of circulating microvesicles through phosphatidylserine-mediated phagocytosis. Together, these results identify the scavenging system for apoptotic cells as a potential therapeutic target to prevent TBI-induced coagulopathy and improve the outcome of TBI.

 

摘要:

凝血障碍在创伤性脑损伤(TBI)患者中很常见,并能预测不良的临床结果。我们已经证明了脑源性的细胞外微囊泡,包括细胞外线粒体,在创伤性脑损伤诱导的凝血障碍的发展中起着关键作用。在此,我们进一步证明了在小鼠模型中,脑损伤前30分钟(预处理)或后30分钟内单次给400 μg/kg剂量的凋亡细胞清除因子lactadherin能预防凝血障碍,凝血障碍通过凝血时间、纤维蛋白溶解、血管内纤维蛋白沉积和肺部微血管出血判断。Lactadherin还能减少脑水肿,改善神经功能,提高生存率。它通过磷脂介导的吞噬作用增强了循环血中微泡的清除,从而达到了这些保护效果。总之,这些结果确定了凋亡细胞的清除系统可作为预防创伤性脑损伤诱导的凝血障碍的潜在治疗靶标,并能改善创伤性脑损伤患者的预后。

 

使用试剂原文信息:Plasma levels of the fibrinolytic product D-dimer were measured with a commercial kit according to the manufacturer’s instructions (Cloud-Clone Corp., Houston, TX).


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