褪黑素抑制脑创伤后炎症反应的机制研究  

Melatonin inhibits inflammatory reaction following traumatic brain injury: a mechanism study

作　　者：丁可[1] 李桃[1] 文立利[1] 王汉东[1] 

机构地区：[1]南京军区南京总医院神经外科,江苏南京210002

出　　处：《中华神经外科疾病研究杂志》2015年第6期501-504,共4页Chinese Journal of Neurosurgical Disease Research

基　　金：国家自然科学基金资助项目(81371357);南京军区南京总医院资助项目(2014040)

摘　　要：目的观察褪黑素在创伤性脑损伤(TBI)后炎症反应中的作用。方法雄性印记控制区(ICR)小鼠,随机分为假手术组(sham)、TBI组、TBI加盐水组(saline)和褪黑素处理组(Mel)(每组24只)。通过自由落体模型使小鼠致伤,于术后24 h分别检测小鼠脑组织含水量、伊文氏蓝含量的变化,并使用酶联免疫吸附法、冰冻切片免疫荧光分别检测促炎细胞因子(白细胞介素-1和肿瘤坏死因子α)和离子钙接头分子-1(IBA-1)的表达。结果 TBI后24 h小鼠脑组织含水量、血脑屏障通透性显著升高;挫伤灶周围皮层促炎细胞因子含量显著升高;挫伤灶周围皮层小胶质细胞活化明显增强;使用褪黑素后,小鼠脑组织含水量、血脑屏障通透性均显著减少,同时褪黑素能够减少TBI后的促炎细胞因子表达、抑制小胶质细胞的活化。结论褪黑素可以缓解TBI后的炎症反应,可能与其抑制小胶质细胞的活化相关。Objective The present study is conducted to evaluate the anti-inflammation of melatonin in an experimental model of traumatic brain injury （TBI）. Methods Imprinting control region （ICR） mice were divided into four groups ： sham group, TBI group, TBI ＋ saline group and TBI ＋ Melatonin group （ n = 24 per group）. A weight-drop model was employed to induce TBI. Brain edema and Evans blue extravasation were measured at 24 h post TBI. Enzyme-linked immunosorbent assay （ELISA） was employed to evaluate pminflammatory cytokine levelsinterleukin-lbeta （IL-Iβ）, tumor necrosis factor-alpha （TNF-α）. Immunofluorescence was designed to investigate the microglial activation. Results The brain edema and blood-brain barrier permeability were significantly aggravated at 24 h after TBI. In addition, the contents of IL-1β and TNF-α were significantly increased and the microglial activation was markedly enhanced at 24 h after TBI. However, melatonin administration was associated with less brain edema and BBB disruption, decreased release of proinllammatory cytokines and markedly restrained microglial activation. Conclusion Melatonin can alleviate the neuroinflammation post-TBI, which may be associated with the inhibition of microglial activation.

关 键 词：创伤性脑损伤 褪黑素 炎症反应 小胶质细胞活化 

分 类 号：R651.15[医药卫生—外科学]