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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 effect of low dose hydrocortisone (HC) on brain dysfunction induced by endotoxin in septic rats and the role of nuclear factor κB (NFκB) signal transduction pathway in pathogenesis. Methods Fifty-four male Wistar rats were randomly divided into three groups: control group (group A) 6, model group (group B) 24, and low-dose HC intervention group (group C) 24. The rat model of sepsis was established by intraperitoneal injection of LPS (1 mg kg). HC6 mg kg was injected into the caudal vein for intervention, and the brains were anesthetized and perfusion fixed at 2, 8, 16 and 24 hours after injection. Group B and C each group of six each. The behavior changes of rats were observed. The hippocampal histological changes were observed by Nissl staining. The expressions of NFκB and IκB in hippocampus were detected by immunohistochemical method and medical image analysis system. Results The behavior changes of rats in the model group were more obvious than those in the control group (P <0.05). The expression of NFκB was significantly up-regulated compared with the control group (P <0.05), and the expression of IκB was decreased (P <0.05), and reached the peak at 8h. In intervention group, behavioral changes and Nissl’s staining were all lighter than those in model group. The expression of NFκB in hippocampus was significantly lower than that in model group (P < 0.05). The expression of IκB in model group was significantly higher than that in model group (P <0.05). Conclusion Low-dose HC can inhibit the expression of NFκB by inducing IκB, and then regulate the histopathological changes and brain dysfunction induced by LPS in sepsis. The NFκB signal transduction pathway plays an important role in the pathogenesis of sepsis.