自由基在幼年鼠内毒素性脑水肿发病机理中的作用及地塞米松、IVIG对其影响的研究

Role of free radicals in brain edema induced by endotoxin in infant rats and the therapeutic effect of dexamethasone and IVIG

目的 探讨总巯基 (TSH)、非蛋白巯基 (NPSH)及丙二醛 (MDA)等自由基在幼年鼠内毒素性脑水肿发病机理中的作用以及地塞米松 (DEX)、IVIG对其干预作用。方法 Wistar鼠 1 2 0只 ,对照组 :2 4只 ,1mg/kg生理盐水腹腔注射 ;单纯内毒素 (LPS)组 :36只 ,1 0mg/kgLPS腹腔注射 ;地塞米松治疗组 (DEX组 ) :36只 ,LPS 1 0mg/kg腹腔注射后 ,立即从尾静脉给予DEX 1 0mg/kg;免疫球蛋白治疗组 (IVIG组 ) :共 2 4只 ,LPS 1 0mg/kg腹腔注射后 ,立即从尾静脉给予IVIG 40 0mg/kg。于不同时间用常规生化方法测定脑组织匀浆中MDA、TSH、NPSH和伊文思蓝 (EB)含量。用干湿法测定脑组织含水量。结果 LPS组脑含水量、EB含量及MDA含量均明显高于对照组 ,而TSH和NPSH含量明显低于对照组 (P <0 0 5或P <0 0 1 ) ;DEX组和IVIG组脑含水量、EB含量及MDA含量与LPS组相比则有明显降低 ,以 6h更明显 (P <0 0 5或P <0 0 1 ) ,而TSH和NPSH含量分别在各时间点上比LPS组明显增高 ,但IVIG对NPSH含量影响与LPS组相比差异无显著性 (P >0 0 5)。结论 自由基参与了幼年鼠内毒素性脑水肿的发生发展 ,初步证实地塞米松和静注免疫球蛋白通过影响自由基 。

Objective Glucocorticoid is considered as an effective drug for prevention and treatment of brain edema and reducing the blood brain barrier (BBB) permeability Intravenous immunoglobulin (IVIG) is frequently used to treat neurological diseases with immune abnormality, its function and potential mechanism on brain edema have not been reported In this study, the roles of the total hydrosulfide group (TSH), non protein hydrosulfide group (NPSH) and malondialdehyde (MDA) in etiology of the endotoxin brain edema in infant rats and the interfering effects of dexamethasone (DEX) and IVIG were investigated Methods In 35 infant rats, 10 mg/kg lipopolysaccharide (LPS) was intraperitoneally injected The same volume of normal saline was injected to 24 control rats Ten mg/kg DEX and 400 mg/kg IVIG were intravenously injected respectively to 36 and 24 infant rats instantly following LPS injection The TSH, NPSH and MDA concentrations and the brain Evans blue contents were detected at different time in the brain tissue The brain water content was measured by drying method Results The brain water, EB and MDA contents after endotoxin injection were significantly higher than those of control group, while the brain TSH, NPSH content were significantly lower than those of control group ( P <0 05 or P <0 01); After treatment with DEX or IVIG, the brain EB, MDA and water content significantly decreased with the peak at 6 h ( P <0 05 or P <0 01), TSH and NPSH significantly increased compared with LPS group However, the NPSH content in IVIG treatment group did not change significantly ( P >0 05) Conclusion Free radicals play a role in the brain edema induced by LPS in infant rats The primary results suggested that DEX and IVIG have therapeutic effect for the endotoxin induced brain edema by affecting the free radicals