Simvastatin accelerates hematoma resolution after intracerebral hemorrhage in a PPARγ-dependent manner

被引：48

作者：

Wang, Yuelong ^{[1
]}

Chen, Qianwei ^{[1
]}

Tan, Qiang ^{[1
]}

Feng, Zhou ^{[1
]}

He, Zhenlin ^{[2
]}

Tang, Jun ^{[1
]}

Feng, Hua ^{[1
]}

Zhu, Gang ^{[1
]}

Chen, Zhi ^{[1
]}

机构：

[1] Third Mil Med Univ, Southwest Hosp, Dept Neurosurg, 30 Gaotanyan St, Chongqing 400038, Peoples R China

[2] First Peoples Hosp Yunnan Prov, Dept Reprod & Genet, Reprod Med Ctr, Kunming 650200, Yunnan, Peoples R China

来源：

NEUROPHARMACOLOGY | 2018年 / 128卷

基金：

中国国家自然科学基金;

关键词：

Intracerebral hemorrhage; Simvastatin; CD36; Microglia/macrophages polarization; PPAR gamma; Erythrophagocytosis; ACTIVATED-RECEPTOR-GAMMA; M1/M2; POLARIZATION; STATIN THERAPY; STROKE; CD36; HOSPITALIZATION; PHAGOCYTOSIS; ABSORPTION; EXPRESSION; INJURY;

D O I：

10.1016/j.neuropharm.2017.10.021

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

To date, the neuroprotective effects of statins on intracerebral hemorrhage (ICH) are not well established. This study explored the effect and potential mechanism of simvastatin treatment on ICH. In the present study, the effects of simvastatin on hematoma absorption, neurological outcome, CD36 expression and microglia polarization were examined in rat model of ICH model. In the meantime, inhibitory effect of PPARy inhibitor GW9662 was investigated following ICH. Additionally, the effect of simvastatin on PPARy activation was also investigated in rat ICH model and primary microglia culture. Much more, the role of PPARy and CD36 in simvastatin-mediated erythrocyte phagocytosis was also detected by using in vivo or in vitro phagocytosis models, respectively. After ICH, simvastatin promoted hematoma absorption and improved neurological outcome after ICH while upregulating CD36 expression and facilitating M2 phenotype polarization in perihematomal microglia. In addition, simvastatin increased PPARy activation and reinforced microglia-induced erythrocyte phagocytosis in vivo and in vitro. All above effects of simvastatin were abolished by PPARy inhibitor GW9662. In conclusion, our data suggested that simvastatin could enhance hematoma clearance and attenuate neurological deficits possibly by activating PPARy. (C) 2017 Elsevier Ltd. All rights reserved.

引用

页码：244 / 254

页数：11

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