小剂量氢化可的松对脓毒症大鼠海马组织HMGB1表达的影响及机制研究  

Effects and its mechanism of low-dose hydrocortisone on late cytokine HMGB1 expression in hippocampus of lipopolysaccharides-induced septic rats

作　　者：武志远[1] 曾建生[2] 樊寻梅[2] 

机构地区：[1]广州市儿童医院PICU,广东广州510120 [2]首都医科大学附属北京儿童医院PICU,北京100045

出　　处：《临床儿科杂志》2009年第8期776-779,共4页Journal of Clinical Pediatrics

摘　　要：目的研究小剂量氢化可的松(HC)对内毒素(LPS)诱导的脓毒症大鼠晚期炎症介质高迁移率蛋白B-1(HMGB1)表达的影响及核因子κB(NF-κB)信号转导途径在发病机制中的作用。方法实验用雄性Wistar大鼠随机分为对照组(A组)、模型组(B组)、小剂量HC干预组(C组)。B组和C组设立2、8、16、24四个时段点,分别为B2、B8、B16、B24、C2、C8、C16、C24组。腹腔注射LPS(1mg/kg)建立脓毒症大鼠模型,尾静脉注射小剂量HC(6mg/kg)作为干预。72只大鼠每组8只采集各组大鼠海马组织,进行蛋白免疫印迹分析检测HMGB1水平。54只大鼠每组6只,采用免疫组化SP法及医学图像分析系统检测大鼠海马NF-κB、IκB的表达。结果HMGB1在A组可见微量表达,B8组表达量始增加,以B16、B24组为高(P<0.05),B组HMGB1表达有持续增加趋势。C组HMGB1表达较B组呈减少趋势,以C16、C24组减少明显,差异有统计学意义(P<0.05)。B组NF-κB表达较A组显著上调,以B8组最高(P<0.05),IκB表达先降低后逐步上升,较A组也明显增加,以B24组为高(P<0.05),C组NF-κB表达较B组显著下调,以C2、C8组为著(P<0.05);IκB表达较B组明显增加,以C8、C16、C24组为著(P<0.05)。结论小剂量HC对晚期炎症介质HMGB1有明显抑制作用,NF-κB信号转导途径在其中起到重要作用。Objective To investigate the effect of low-dose hydrocortisone （HC） on late cytokine HMGB1 expression in bippocampus of lipopolysaccharide （LPS） induced septic rats, and the role of nuclear factor kappa B （NF-KB） signal transcription pathway in the pathogenesis. Methods Experimental Wistar male rats were randomly divided into 3 groups： control group （group A, n = 9）, model group （group B）, low-dose HC treatment group （group C）. Groups B and C were subdivided into 2, 8, 16, 24 hours subgroups after LPS injection, with 8 rats in each subgroup. The septic rat model was established by intraperitoneal injection of LPS （ 1 mg/kg） , as the intervention by caudal vein injection of low-dose HC （6 mg/kg）. HMGB1 contents of hippocampus tissue were analyzed by Western blotting. NF-KB, IKB expression in hippocampus were determined by immunohistochemistry in total 54 rats, with 6 rats in each subgroup. Results Expression of HMGB1 content of hippocampus tissue was less in group A, and higher in group B16 and group B24 （P 〈 0.05） , however, expression of HMGBI content decreased in group C compared with that of group B, significantly in group C16, group C24 （P 〈 0.05）. NF-κB expression of group B was up-regulated compared with that of group A, especially in B8 （P 〈 0.05）. IκB expression showed a down-regulation firstly and gradually elevated to the peak at the time point of B24 （P 〈 0.05 ）. NF-κB expression of group C was down-regulated compared with group B, particularly in group C2 and group C8 （P 〈 0.05）. IκB expression was significantly increased in group C8, C16, C24 （all P 〈 0.05 ）. Conclusions Low-dose HC inhibits the late cytokine HMGB 1 expression significantly in LPS-induced septic rats. NF-κB/IκB signal transcription pathway might play an important role in the pathogenesis.

关 键 词：高迁移率蛋白B-1 氢化可的松 内毒素 脓毒症 核因子-ΚB 大鼠 

分 类 号：R459.7[医药卫生—急诊医学]