Role of Regulatory T cells in Atorvastatin Induced Absorption of Chronic Subdural Hematoma in Rats
Role of Regulatory T cells in Atorvastatin Induced Absorption of Chronic Subdural Hematoma in Rats
复制标题
调节性 T 细胞在阿托伐他汀诱导大鼠慢性硬膜下血肿吸收中的作用
DOI：
10.14336/ad.2018.0926
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发表时间：
2019-10-01
影响因子：
7.4
通讯作者：
Jiang, Rongcai
中科院分区：
文献类型：
--
作者：
Quan, Wei;Zhang, Zhifei;Jiang, Rongcai
慢性硬膜下血肿（CSDH）是一种复发率很高的神经系统疾病。阿托伐他汀是一种有效的治疗高脂血症的药物，并已知可改善脑出血后的神经功能结局。既往研究报道阿托伐他汀治疗可促进CSDH血肿吸收，但其机制尚不清楚。在这项研究中，我们研究了阿托伐他汀的抗炎作用是否介导CSDH的吸收。将144只雄性Wistar大鼠（6月龄）随机分为以下组：1）假手术对照组，2）治疗组：CSDH +阿托伐他汀组，3）溶剂对照组：CSDH +生理盐水组。CSDH术后每天口服阿托伐他汀或生理盐水19天。T2 WI MRI用于评估研究期间CSDH体积变化。流式细胞术和免疫组织化学染色检测调节性T细胞（Treg）的数量。ELISA法检测血肿边缘细胞因子水平。分别采用足错试验和Morris水迷宫试验评价神经功能和认知功能。阿托伐他汀治疗后14、21天T2 WI血肿体积明显减少，与生理盐水治疗组相比，阿托伐他汀治疗组血肿吸收速度明显加快（P<0.05）。阿托伐他汀治疗后3 ~ 21 d，血循环和血肿边缘Treg数量明显增加。阿托伐他汀治疗后，血肿边缘区IL-6、IL-8、TNF-α水平明显降低，IL-10水平明显升高。与溶剂处理组相比，阿托伐他汀处理还改善了神经功能和认知结果。阿托伐他汀可诱导CSDH在大鼠体内的抗炎反应，并增加循环和脑中的Treg，这可能有助于加速CSDH在大鼠体内的吸收。
Chronic subdural hematoma (CSDH) is a neurological disorder with a substantial recurrence rate. Atorvastatin is an effective drug for treating hyperlipidemia and known to improve neurological outcome after intracerebral hemorrhage. Previous studies have reported that atorvastatin treatment promotes hematoma absorption in CSDH, while the underlying mechanisms remain unclear. In this study, we investigated whether the anti-inflammatory effects of atorvastatin mediate absorption of CSDH. 144 male, Wistar rats (6 months old) were randomly divided into the following groups: 1) sham surgery control, 2) treatment: CSDH + atorvastatin, and 3) vehicle control: CSDH + saline. Atorvastatin or saline was orally administered daily for 19 days after CSDH procedure. A T2WI MRI was used to evaluate CSDH volume changes during the time course of the study. Flow cytometry and immunohistochemical staining were used to measure the number of regulatory T cells (Treg). ELISA was used to measure cytokine level in the hematoma border. Neurological function and cognitive outcome were evaluated using Foot-Fault test and Morris Water Maze test, respectively. When compared to saline treatment, atorvastatin treatment accelerated the absorption of CSDH as indicated by decreased hematoma volume in T2WI MRI data on 14th and 21st day after CSDH (P<0.05). Atorvastatin treatment significantly increased the number of Treg in circulation and hematoma border from 3rd to 21st day after CSDH. Atorvastatin treatment significantly decreased the levels of interleukins (IL-6 and IL-8) and tumor necrosis factor-α (TNF-α), but increased IL-10 level in the hematoma border. Atorvastatin treatment also improved neurological function and cognitive outcome compared to vehicle treated group. Atorvastatin induced anti-inflammatory responses and increased Treg in circulation and brain which may contribute to the accelerated CSDH absorption in rats.