Atorvastatin enhances angiogenesis to reduce subdural hematoma in a rat model
Atorvastatin enhances angiogenesis to reduce subdural hematoma in a rat model
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阿托伐他汀可增强血管生成，从而减少大鼠模型中的硬膜下血肿。
DOI：
10.1016/j.jns.2016.01.017
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发表时间：
2016-03-15
影响因子：
4.4
通讯作者：
Zhang, Jian Ning
中科院分区：
文献类型：
--
作者：
Wang, Dong;Li, Tuo;Zhang, Jian Ning
背景与目的：他汀类药物具有降血脂、抗炎、促进血管生成等作用。由于血管生成对硬膜下血肿(SDH)的吸收至关重要，因此我们假设阿托伐他汀促进血管生成以促进血肿的吸收。方法：成年Wistar大鼠诱导硬膜下血肿(SDH)，每天给予3 mg/kg、8 mg/kg阿托伐他汀或生理盐水，连续7d。用流式细胞仪检测大鼠外周血中CD34+/CD133+内皮祖细胞的水平，核磁共振成像(MRI)检测血肿体积，以及认知功能的变化。结果：与大剂量阿托伐他汀组和生理盐水组比较，小剂量阿托伐他汀组SDH体积显著减少，神经功能评分明显改善。与上述结果一致，小剂量阿托伐他汀可增加SDH壁结缔组织中血管生成素-1和血管内皮生长因子的表达，减少MMP9的表达，从而增加血管密度，促进血管成熟。结论：小剂量阿托伐他汀能有效降低SDH，改善神经功能障碍，主要是通过促进血管生成和血管成熟实现的。(C)2016年，由爱思唯尔出版。
Background and purpose: Statins are active in reducing plasma lipids, suppressing inflammation and promoting angiogenesis. Because angiogenesis is critical for the absorbance of subdural hematoma (SDH), we hypothesize that atorvastatin promotes angiogenesis to enhance hematoma absorption.Methods: SDH was induced in adult Wistar rats and treated with 3 mg/kg, 8 mg/kg of atorvastatin, or vehicle saline daily for 7 days. The treated rats were examined for the level of CD34+/CD133+ endothelial progenitor cells (EPCs) in the circulation by flow cytometry, hematoma volumes by magnetic resonance imaging (MRI), and changes in cognitive functions. We also examined angiogenesis in the hematoma wall by transmission electronic microscopy and immunohistochemistry for the expression of vascular endothelial growth factor (VEGF), matrix metalloprotease 9 (MMP 9) and angiopoietin.Results: SDH volume was significantly reduced and neurological deficits improved in rats receiving the low dose atorvastatin compared to those receiving either the high dose of atorvastatin or saline. Consistent with these outcome measures, the low dose atorvastatin increased the expression of angiopoient-1 and VEGF and reduced MMP9 expression in the connective tissue of the SDH wall, resulting in an increased vascular density and enhanced vascular maturation.Conclusions: The low-dose atorvastatin is effective in reducing SDH and improving neurological deficits in a rat model, primarily by promoting angiogenesis and vascular maturation. (C) 2016 Published by Elsevier B.V.