Li Tuo, Wang Dong, Tian Ye, Yu Huijie, Wang Yi, Quan Wei, Cui Weiyun, Zhou Lei, Chen Jieli, Jiang Rongcai, Zhang Jianning
Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052, China; Tianjin Neurological Institute, Tianjin 300052, China; Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin 300052, China; Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin 300052, China.
Tianjin Neurological Institute, Tianjin 300052, China.
J Neurol Sci. 2014 Jun 15;341(1-2):88-96. doi: 10.1016/j.jns.2014.04.009. Epub 2014 Apr 13.
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).
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, 3mg/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.
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-α and IL-6 level as well as VEGF gene expression.
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.
众所周知,炎症在很大程度上影响慢性硬膜下血肿(CSDH)的形成。阿托伐他汀除了具有降胆固醇功能外,还具有抑制炎症和促进血管生成的多种作用。因此,阿托伐他汀可能诱导抗炎作用并促进硬膜下血肿(SDH)的治疗效果。
成年雄性Wistar大鼠接受SDH手术,并通过磁共振成像(MRI)确认成功建立SDH模型。在SDH诱导后6小时开始治疗。对于治疗,将患有SDH的大鼠随机分为生理盐水组(对照组,大鼠接受生理盐水治疗,n = 29)和阿托伐他汀组(大鼠接受阿托伐他汀治疗,3mg/kg/天,n = 30)。分别通过MRI测量治疗前以及初始治疗后第2天和第7天的病变体积。动态评估SDH诱导前以及初始治疗后第1、3、5和7天的行为。在初始治疗后第2天和第7天,测量新生膜和SDH病变中的基因表达、细胞因子分泌以及中性粒细胞数量和血管密度。
发现与接受生理盐水治疗的大鼠相比,接受阿托伐他汀治疗的SDH大鼠行为恢复更好(p<0.05)。通过MRI扫描发现,与生理盐水相比,阿托伐他汀给药可使SDH体积更快消除。借助新生膜的显微镜检查,发现阿托伐他汀组中CD31 +新生血管的密度明显高于生理盐水组,且阿托伐他汀组中的中性粒细胞数量少于生理盐水组。与生理盐水治疗相比,阿托伐他汀治疗未改变IL-10的表达和分泌,但它显著降低了TNF-α和IL-6水平以及VEGF基因表达。
阿托伐他汀治疗可能通过其抗炎作用消除SDH并改善大鼠的神经功能。因此,表明他汀类药物诱导的炎症调节可能在大鼠SDH消除和功能恢复中起重要作用。