丙戊酸对大鼠颅脑损伤局部炎性反应的抑制作用

Effects of valproic acid on inflammatory reaction of rats with traumatic brain injury

目的 检测丙戊酸（VPA）干预颅脑损伤大鼠后不同时间点脑组织内肿瘤坏死因子-α（TNF-α）和白细胞介素（IL）-1β蛋白表达及动态变化,探讨丙戊酸对颅脑损伤大鼠局部炎性反应的影响.方法 将健康Sprague-Dawley （SD）雄性大鼠150只随机分成正常对照组、单纯损伤组、VPA治疗组,建立大鼠闭合性颅脑损伤模型并进行干预,颅脑损伤后4h、1、2、3、4、7d应用免疫荧光技术检测各组脑组织内TNF-α和IL-1 β蛋白表达,应用酶联免疫吸附试验法测定各组不同时间点脑组织内TNF-α和IL-1β的动态变化.结果 颅脑损伤后4h单纯损伤组和VPA治疗组脑组织内TNF-α阳性细胞数分别为（16.80±2.44）、（16.56 ±2.78）个/高倍镜视野,均高于正常对照组（2.36±0.54）个/高倍镜视野,差异有统计学意义（P＜0.05）.颅脑损伤后3 d VPA治疗组脑组织内TNF-α阳性细胞数为25.37±1.28,低于单纯损伤组的（57.48±1.98）个/高倍镜视野,差异有统计学意义（P＜0.05）.颅脑损伤后4h单纯损伤组和VPA治疗组脑组织中IL-1β蛋白浓度分别为（89.23±3.76）、（88.35±3.97） μg/L,均高于正常对照组（47.35±3.76） μg/L,差异有统计学意义（P＜0.05）;颅脑损伤后3 d VPA治疗组脑组织中IL-1β蛋白浓度为（103.83 ±3.26） μg/L,低于单纯损伤组的（132.53 ±3.21） μg/L,差异有统计学意义（P＜0.05）.结论 丙戊酸钠通过下调TNF-α和IL-1β的表达抑制颅脑损伤大鼠局部炎性反应.

Objective To detect protein expression and dynamic alterations of tumor necrosis factor （TNF）-α and interleukin （IL）-1 β in brain tissue of rats with experimental traumatic brain injury after VPA intervention,To explore the roles of VPA in reducing the inflammatory response of rats with TBI.Methods One hundred and fifty healthy male Sprague-Dawley rats were randomly divided into normal control group,the simple trauma group and VPA treated group.Rat model of closed head injury was established and then interfered by VAP.Immunofluorescence was employed to detect protein expression of TNF-α and IL-1β in brain cells within each group at 4 h,1,2,3,4,7 d after brain injury.Enzyme-linked immunosorbent assay （ELISA） was performed to detect the dynamic changes of TNF-α and IL-1 β in brain tissue within each group at different time points.Results The positive cells of TNF-α in brain tissue of simple trauma group and VPA treated group which was （16.80 ± 2.44）,（16.56 ± 2.78）/HP were more than （2.36 ± 0.54）/HP of normal control group 4 hour after experimental brain injury and the differences were statistically significant （P 〈 0.05）.The positive cells of TNF-α （25.37 ± 1.28）/HP in brain tissue of VPA treated groupwas was less than （57.48 ± 1.98）/HP of simple trauma group 3 day after brain injury.The difference was statistically significant （P 〈 0.05）.Enzyme-linked immunosorbent assay test：The protein concentrations of IL-1 β in brain tissue of simple trauma group and VPA treated group which was （89.23 ±3.76）,（88.35 ±3.97） μg/L,were higher than （47.35 ±3.76） μg/L of normal control group 4 hour after experimental brain injury and the differences were statistically significant （P 〈 0.05）.The protein level of IL-1β （103.83 ± 3.26） μg/L,in brain tissue of VPA treated group was lower than （132.53 ±3.21） μg/L of simple trauma group 3 day after brain injury and the difference was statistically significant （P 〈 0.05）.Conclusion Valproic acid could inhibit inflammatory reaction in brain tissue of rats with traumatic brain injury by down regulation of the protein expression of TNF-α and IL-1 β.