肿瘤坏死因子-α刺激基因-6蛋白对脑梗死早期炎症反应和血脑屏障的影响  

Effect of tumor necrosis factor-α stimulated gene-6 on early inflammation and blood brain barrier after ischemic stroke

作　　者：刘扬[1] 余列[1] 卜淑芳[1] 刘喜灿[1] 

机构地区：[1]郑州大学附属郑州中心医院神经内科,郑州450052

出　　处：《中华神经医学杂志》2015年第5期443-447,共5页Chinese Journal of Neuromedicine

摘　　要：目的 探讨肿瘤坏死因子-α刺激基因-6蛋白（TSG-6）对脑梗死早期炎症反应和血脑屏障的影响.方法 将90只雄性C57BL/6j小鼠按随机数字表法分为假手术组、溶剂治疗组、TSG-6治疗组,每组30只;后2组采用线栓法制备成大脑中动脉栓塞模型,造模成功后TSG-6治疗组小鼠立即通过尾静脉注射含有TSG-6（50 μg/只）PBS 200 μL,溶剂治疗组仅注射等体积PBS.脑梗死1、3d后采用改良神经功能缺损评分（mNSS）评价各组小鼠神经功能;脑梗死3d后采用氯化三苯四唑（TTC）染色评价脑梗死体积,干湿重法检测脑组织含水量,荧光分光光度法评估伊文氏蓝（EB）在梗死侧脑组织的渗出量,紫外分光光度法检测组过氧化物酶（MPO）活性,Western blotting检测基质金属蛋白酶-9（MMP-9）、高迁移率族蛋白B1（HMGB1）和Toll样受体4（TLR4）的表达量.结果 脑梗死3d后,与溶剂治疗组mNSS评分（7.923 ±2.138）、脑梗死体积[（36.883±8.553）％]、脑组织EB含量[（11.867±4.135） μg/g]、脑组织含水量[（80.467±7.045）％]、MPO活性[（112.617±26.782）mU/g]以及梗死侧脑组织HMGB1 （0.861 ±0.137）、TLR4（0.833±0.193）和MMP-9（0.910±0.156）表达量比较,TSG-6治疗组小鼠mNSS评分（5.253±1.712）、脑梗死体积[（26.100±5.640）％]、脑组织EB含量[（7.233±3.434） μg/g]、脑组织含水量[（71.667±6.518）％]、MPO活性[（70.383±17.558） mU/g]以及梗死侧脑组织HMGB1 （0.503±0.230）、TLR4（0.482±0.159）和MMP-9（0.611±0.170）表达量明显降低或减小,差异均有统计学意义（P＜0.05）.结论 TSG-6可显著减少HMGB1、TLR4的表达和中性粒细胞的浸润,进而减少MMP-9的表达发挥血脑屏障保护作用,减轻脑水肿和脑梗死体积,促进神经功能的恢复.Objective To explore the effects of tumor necrosis factor-α stimulated gene-6 （TSG-6） on early inflammation and blood brain barrier （BBB） in mice after ischemic stroke （IS）.Methods A total of 90 healthy male C57BL/6j mice were randomly divided into sham-operated group （n=30）,vehicle group （n=30） and TSG-6 treatment group （n=30）;the middle cerebral artery occlusion models （IS） in the later two groups were established with suture emboli method;50 μg TSG-6 or PBS was immediately injected into mice via tail vein after IS.Neurological function deficits were assessed by modified neurological severity scale （mNSS） one and three days after IS;infraction volume was examined by triphenyl tetrazolium chloride （TTC） staining,the changes of brain water content were examined by wet and dry weight method,evans blue （EB） extravasation was assessed by means of EB fluorescent quantitation,myeloperoxidase （MPO） activity was tested by ultraviolet specterphotometry,and Western blotting was used to detect the expressions of matrix metalloproteinase-9 （MMP-9）,high-mobility group protein box 1 （HMGB1） and toll-like receptor 4 （TLR4） three days after IS.Results Three days after IS,the mNSS scores （5.253±1.712）,infraction volume （[26.100±5.640]%）,EB extravasation （[7.233± 3.434] μg/g）,brainwater content （[71.667±6.518]%）,MPO activity （[70.383±17.558] mU/g） and HMGB1,TLR4 and MMP-9 expressions （0.503±0.230,0.482±0.159 and 0.611±0.170） in the TSG-6 treatment group were significantly lower or smaller than those in the vehicle group （[7.923±2.138],（[36.883±8.553]%）,（[11.867±4.135] μg/g）,（[80.467±7.045]%）,（[112.617±26.782] mU/g）,[0.861± 0.137],[0.833 ±0.193] and [0.910 ±0.156]） three days after IS （P〈0.05）;the expressions of MMP-9 （0.611±0.170）,HMGB1 （0.503±0.230） and TLR4 （0.482±0.159） in mice of TSG-6 treatment group were significantly down-regulated as compared with those in vehicle group those days af

关 键 词：肿瘤坏死因子-α刺激基因-6蛋白 脑梗死 炎症反应 血脑屏障 

分 类 号：R743.3[医药卫生—神经病学与精神病学]