摘要
目的评价右美托咪定对脓毒症小鼠脑损伤的影响,并初步探讨其可能机制。方法雄性ICR(institute of cancer research)小鼠180只,6-8周龄,重20-25 g,采用随机数字表法分为4组:假手术组(S组)、假手术组+右美托咪定组(S+D组)脓毒症组(CLP组)、脓毒症+右美托咪定组(CLP+D组)。S+D组和CLP+D组于术后0,3,6 h腹腔注射右美托咪定20μg/kg。于CLP或假手术后6,12,24 h时,取脑组织采用伊文氏蓝染色和检测脑组织含水量来观察各组小鼠血脑屏障的破坏情况,并检测脑组织中肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)和高迁移率族蛋白B1(high mobility group box 1,HMGB1)的水平。于CLP或假手术后24 h时,取脑组织,采用Western blot法检测各组小鼠脑组织紧密连接蛋白ZO-1和Claudin-5表达的改变,并行HE染色观察脑组织病理学改变。结果 S组和S+D组各项指标差异无统计学意义(P>0.05)。与S组比较,CLP组于CLP后6,12和24 h时EB含量和脑组织含水量升高,脑组织中TNF-α和HMGB1的水平升高(P<0.05);于CLP后24 h时,脑组织紧密连接蛋白ZO-1和Claudin-5表达下调(P<0.05),海马CA1区神经元排列紊乱、胞质深染,核固缩,结构不清晰。与CLP组相比,CLP+D组于CLP后6,12,24 h EB含量和脑组织含水量降低,脑组织中TNF-α和HMGB1的水平降低(P<0.05);于CLP后24 h时,脑组织紧密连接蛋白ZO-1和Claudin-5表达上调(P<0.05),海马CA1区神经元排列尚规整,受损神经元减少。结论右美托咪定可通过减轻脓毒症小鼠血脑屏障的破坏来改善脑损伤,其机制与抑制炎症反应有关。
Objective To investigate the effect of dexmedetomidine on brain injury in septic mice. Methods One hundred and eighty 6 - 8-week-old ICR （ institute of cancer research ） mice, weighing 20 - 25 g, were randomly divided into 4 groups ： sham （ S ） group, sham ＋ dexmedetomidine group （S ＋ D）, cecal ligation and puncture （CLP）group and cecal ligation and puncture ＋ dexmedetom-idine （ CLP ＋ D）group. Sepsis was produced by cecal ligation and puncture （CLP）. The mice were intraperitoneally injected with dexmc- detomidine 20 μg/kg at 0,3 and 6 h after CLP or sham operation,respectively. At 6,12 and 24 h after CLP or sham operation, brain tissues were removed to detect the exudation of evans blue（EB） and water contents, and the concentration of TNF-α and HMGB1. At 24 h after CLP or sham operation, the expression of ZO-1 and Claudin-5 in brain tissues was detected by Western blot and the histopatho- logic changes were observed by hematoxylin-eosin staining. Results There was no statistical difference in all aspects between S group and S ＋ D group（ P 〉 0.05 ）. Compared with S group ,the contents of EB and water and the concentrations of TNF-α and HMGB1 in brain tissues were significantly increased in CLP group at 6,12 and 24 h after CLP operation（P 〈0.05 ） ,while the expression of ZO-1 and Claudin-5 in brain tissues was significantly decreased at 24 h after CLP operation （ P 〈 0. 05）. The loosen arrangement, dark cytoplasm and nuclear pyknosis were observed in the hippocampal CA1 region in CLP group at 24 h after CLP operation. Compared with CLP group, the contents of EB and water and the concentrations of TNF-α and HMGB1 in brain tissues were significantly decreased in CLP ＋ D group at 6,12 and 24 h after CLP operation（ P 〈 0.05 ） ,while the expression of ZO-1 and Claudin-5 in brain tissues was significantly increased at 24 h after CLP operation（P 〈 0.05）. The arrangement of neurons was nearly regular and the damaged neurons were decreased in the hi
出处
《山西医科大学学报》
CAS
2015年第2期143-147,192,共6页
Journal of Shanxi Medical University
关键词
右美托咪定
脓毒症
血脑屏障
炎症
dexmedetomidine
sepsis
blood-brain barrier
inflammation
