小剂量氢化可的松对脓毒症大鼠脑功能障碍的影响及机制  

Effects and mechanisms of low-dose hydrocortisone on brain dysfunction in LPS- induced sepsis in rats

作　　者：武志远[1] 曾建生[1] 樊寻梅[1] 

机构地区：[1]首都医科大学附属北京儿童医院ICU,北京100045

出　　处：《中华急诊医学杂志》2006年第6期489-493,共5页Chinese Journal of Emergency Medicine

摘　　要：目的研究小剂量氢化可的松(HC)对内毒素诱导的脓毒症大鼠脑功能障碍的影响及核因子κB(NFκB)信号转导途径在发病机制中的作用。方法54只雄性Wistar大鼠随机分为三组:对照组(A组)6只、模型组(B组)24只、小剂量HC干预组(C组)24只。腹腔注射LPS(1mg kg)建立脓毒症大鼠模型,尾静脉注射HC6mg kg作为干预,分别于注射后2、8、16、24h麻醉并灌注固定取脑。B组和C组每时段各6只。观察大鼠行为学改变;尼氏染色观察大鼠海马组织学变化;采用免疫组化方法及医学图像分析系统检测大鼠海马NFκB,IκB的表达。结果模型组大鼠行为学改变较明显,表现嗜睡、拒食、呼吸增快、竖毛、体重下降;尼氏染色病理变化明显;NFκB表达较对照组显著上调(P<0.05),IκB表达先降低后逐渐上升,较对照组也明显增加(P<0.05),8h时段最高;干预组:大鼠行为学改变、尼氏染色结果均较模型组轻;海马NFκB表达较模型组显著下调(P<0.05);IκB表达较模型组明显增加(P<0.05)。结论小剂量HC可通过诱生IκB抑制NFκB的表达,进而调控LPS诱导的脓毒症脑组织学改变和脑功能障碍,NFκB信号转导途径在其发病机制中起重要作用。Objective To investigate the effects of low-dose hydrocortisone on brain dysfunction in LPS-induced sepsis rats and the role of nuclear factor kappa B （NF-κB） signal transcription pathway in the pathogenesis. Methods Fifty-four rats were randomly divided into 3 groups： control group （A group, n = 6）, model group （B group, n = 24）, low-dese HC treatment group （C group, n = 24）. The septic rat model was established by intra-peritoneal injection of LPS （ 1 mg/kg）, the intervention was by caudal vein injection of low-dose HC （6 mg/kg）, each of B and C group was subdivided into 2, 8, 16, 24 hours after LPS injection （ n = 6）. At serial time points, the animals in each group were sacrificed , brain tissue samples were harvested to determine NF-κB, IκB expression in hippocarnpus by immunohistochemistry. Also, the changes of behaviors were observed and the histopathological changes were investigated by Nissl stain. Results In model group （B group） ： lethargy, anorexia, tachypnea, piloerection, loss of body weight were all more obvious than control groups. Nissl stain showed significant histopathological changes; NF-κB expression was up regulated compared with control group （P〈0.05）, IκBexpression showed a down regulation firstly and escalated gradually before the peak of 8 hours time point peak （ P〈0.05）. Low-dose HC treatment group （C group） ： the changes of behaviors, Nissl histopathological changes showed improvements compared with model group. NF-κB expression was down regulated compared with model group （ P〈0.05） whilst IκB expression was prominently enhaned （ P 〈 0.05）. Conclusion Low-dose HC inhibited the NF-IκB expression by inducing the IκB expression, and then causing brain dysfunction in the septic rats. The NF-κB/IκB signal transcription pathway may have very important role in the pathogencsis of brain dysfunction in sepsis.

关 键 词：核因子-ΚB 氢化可的松 内毒素 脓毒症 海马 

分 类 号：R965[医药卫生—药理学]