Simvastatin Promotes Hematoma Absorption and Reduces Hydrocephalus Following Intraventricular Hemorrhage in Part by Upregulating CD36
Simvastatin Promotes Hematoma Absorption and Reduces Hydrocephalus Following Intraventricular Hemorrhage in Part by Upregulating CD36
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辛伐他汀部分通过上调 CD36 促进血肿吸收并减少脑室内出血后的脑积水
DOI：
10.1007/s12975-017-0521-y
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发表时间：
2017-08-01
影响因子：
6.9
通讯作者：
Chen, Zhi
中科院分区：
文献类型：
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作者：
Chen, Qianwei;Shi, Xia;Chen, Zhi
我们先前发现，脑室内出血（IVH）后血肿通过增加铁沉积和加重室管膜纤毛损伤而使脑积水恶化；因此，促进血肿吸收可能是治疗IVH的一种有前景的策略。最近，一些研究表明辛伐他汀具有加速血肿吸收的能力。因此，本研究旨在检测辛伐他汀对大鼠IVH的疗效。通过自体血注射在成年雄性Sprague - Dawley大鼠中诱导伴有脑室扩展的脑出血。在IVH后1天开始口服辛伐他汀或安慰剂，然后每日给药持续1周。在IVH后的第1、3、7、14和28天进行磁共振成像（MRI）研究以测量颅内血肿和侧脑室的体积。分别在第1 - 7天和第23 - 28天评估运动和神经认知功能。在第28天检测铁沉积、铁相关蛋白表达、室管膜损伤和组织学情况。在IVH后第3天使用蛋白质印迹法和免疫荧光法检测CD36清道夫受体（促进吞噬作用）的表达。辛伐他汀显著提高了血肿吸收率，减少了脑室体积，并减轻了IVH后的神经功能障碍。此外，与对照组相比，辛伐他汀组观察到铁蓄积更少，纤毛存活更多。而且，在给予辛伐他汀后，在血肿周围检测到更高的CD36表达。辛伐他汀显著增强了实验性IVH后的脑血肿吸收，减轻了脑积水，并改善了神经功能恢复，这可能部分是通过上调CD36表达实现的。我们的数据表明，早期使用辛伐他汀可能是IVH患者的一种新的治疗方法。
We previously found that hematoma worsens hydrocephalus after intraventricular hemorrhage (IVH) via increasing iron deposition and aggravating ependymal cilia injury; therefore, promoting hematoma absorption may be a promising strategy for IVH. Recently, some investigations imply that simvastatin has the ability of accelerating hematoma absorption. Thus, this study was designed to examine the efficacy of simvastatin for IVH in rats. Intracerebral hemorrhage with ventricular extension was induced in adult male Sprague-Dawley rats after autologous blood injection. Simvastatin or vehicle was administered orally at 1 day after IVH and then daily for 1 week. MRI studies were performed to measure the volumes of intracranial hematoma and lateral ventricle at days 1, 3, 7, 14, and 28 after IVH. Motor and neurocognitive functions were assessed at days 1 to 7 and 23 to 28, respectively. Iron deposition, iron-related protein expression, ependymal damage, and histology were detected at day 28. Expression of CD36 scavenger receptor (facilitating phagocytosis) was examined at day 3 after IVH using western blotting and immunofluorescence. Simvastatin significantly increased hematoma absorption ratio, reduced ventricular volume, and attenuated neurological dysfunction post-IVH. In addition, less iron accumulation and more cilia survival was observed in the simvastatin group when compared with the control. What's more, higher expression of CD36 was detected around the hematoma after simvastatin administration. Simvastatin significantly enhanced brain hematoma absorption, alleviated hydrocephalus, and improved neurological recovery after experimental IVH, which may in part by upregulating CD36 expression. Our data suggest that early simvastatin use may be a novel therapy for IVH patients.