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.
出处
《临床儿科杂志》
CAS
CSCD
北大核心
2009年第8期776-779,共4页
Journal of Clinical Pediatrics