Effects of atorvastatin on the inflammation regulation and elimination of subdural hematoma in rats

Effects of atorvastatin on the inflammation regulation and elimination of subdural hematoma in rats
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阿托伐他汀对大鼠硬膜下血肿炎症调节及消除作用

DOI:
10.1016/j.jns.2014.04.009
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发表时间:
2014-06-15
影响因子:
4.4
通讯作者:
Zhang, Jianning
Zhang, Jianning
中科院分区:
医学3区
文献类型:
--
作者:
Li, Tuo;Wang, Dong;Zhang, Jianning

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背景与目的:炎症在很大程度上影响慢性硬膜下血肿(CSDH)的形成。阿托伐他汀除具有降胆固醇作用外,还具有抑制炎症、促进血管新生等多种作用。因此,阿托伐他汀可能会诱导抗炎作用,并促进治疗效果的硬膜下血肿(SDH)。方法:成年雄性Wistar大鼠进行SDH和成功建立SDH的磁共振成像(MRI)证实。SDH诱导后6小时开始治疗。治疗方法:将SDH大鼠随机分为生理盐水组(对照组,给予生理盐水,n = 29)和阿托伐他汀组(阿托伐他汀组,给予阿托伐他汀,3 mg/kg/d,n = 30)。分别于治疗前、治疗后第2天和第7天通过MRI测量病灶体积。动态观察SDH诱导前及诱导后第1、3、5、7天的行为学变化。结果:阿托伐他汀组SDH大鼠行为学恢复明显优于生理盐水组(p < 0.05),且与对照组比较,差异有显著性(p < 0.05)。通过MRI扫描,发现阿托伐他汀比生理盐水更快地消除SDH体积。新生膜显微镜下观察,阿托伐他汀组CD 31+新生血管密度明显高于生理盐水组,嗜中性粒细胞数量明显少于生理盐水组。与生理盐水组相比,阿托伐他汀组IL-10的表达和分泌无明显变化,但显著降低TNF-α和IL-6的水平及VEGF基因的表达。结论:阿托伐他汀可能通过抗炎作用消除SDH,改善神经功能。提示他汀类药物诱导的炎症调节可能在大鼠SDH清除和功能恢复中起重要作用。(C)2014作者由爱思唯尔公司出版
Background and purpose: It is well known that inflammation influence chronic subdural hematoma (CSDH) formation to a large extent. Atorvastatin has pleiotropic effects on restraining inflammation and promoting angiogenesis besides its cholesterol-lowering function. Hence, atorvastatin may induce anti-inflammation effects and facilitate therapeutic effects for subdural hematoma (SDH).Methods: Adult male Wistar rats were subjected to SDH and successful establishment of SDH was confirmed by magnetic resonance imaging (MRI). The treatment was initiated 6 hours after SDH induction. For the treatment rats suffering SDH were randomly divided into saline group (the control group, rats were treated by saline, n = 29) and atorvastatin group (rats were treated by atorvastatin, 3 mg/kg/day, n = 30). The volume of lesion before treatment as well as on day 2 and day 7 after initial treatment was measured by MRI, respectively. The behaviors before SDH induction and on the days 1, 3, 5 and 7 after the initial treatment were dynamically evaluated. Gene expression, cytokine secretion and the number of neutrophilic granulocyte and vascular density were measured in both neomembrane and SDH lesion on the day 2 and day 7 after the initial treatment.Results: It was found that the SDH rats treated by atorvastatin had a better behavior recovery compared to the ones treated by saline (p < 0.05). By virtue of MRI scanning, it was revealed that SDH volumes were eliminated at a high speed by administration of atorvastatin than that of saline. With the help of the microscopic examination in the neomembrane, it was detected that the density of CD31 + neovasculars in the atorvastatin group was significantly higher than that in the saline group and the number of neutrophilic granulocyte in the atorvastatin group is less than that in the saline group. In comparison with saline treatment the atorvastatin treatment did not change IL-10 expression and secretion, but it significantly decreased TNF-alpha and IL-6 level as well as VEGF gene expression.Conclusions: Atorvastatin treatment may eliminate SDH and improve the neural function of the rats through its anti-inflammatory effects. Hence, it indicated that statin induced inflammatory modulation might play a significant role in rats' SDH elimination and the functional recovery. (C) 2014 The Authors. Published by Elsevier B.V.