乌司他丁对心肺复苏后兔脑组织氧化应激损伤的影响

Effects of UTI on oxidative stress damage in rabbit brain tissues after cardiopulmonary resuscitation

目的:观察乌司他丁(ulinastatin,UTI)对心肺复苏(cardiopulmonary resuscitation,CPR)后新西兰兔脑组织氧化应激损伤的影响。方法:(1)建立新西兰兔心脏停搏(cardiac arrest,CA)模型,自主循环恢复(return ofspontaneous circulation,ROSC)后24 h内连续采血监测血浆丙二醛(malondialdehyde,MDA)和还原型谷胱甘肽(glu-tathione,GSH)的水平;(2)48只新西兰兔建立CA模型,ROSC后随机分为模型组(model组)和UTI治疗组,观察UTI对大脑皮层和海马内MDA、GSH含量和神经元凋亡的影响,观察UTI对大脑皮层核因子E2相关因子2(nucle-ar factor E2-related factor 2,Nrf2)表达的影响。结果:ROSC后2 h血浆MDA达高峰,GSH降低到较低水平;UTI显著抑制ROSC后大脑皮层和海马MDA水平的升高,提高GSH含量。UTI促进了ROSC后脑组织Nrf2的表达。Model组大脑皮层及海马CA1～CA3区的凋亡神经元数明显多于UTI组。结论:UTI可升高ROSC后兔脑组织GSH水平,降低MDA含量,增加Nrf2的表达,减少神经元的凋亡。

AIM： To investigate the effects of ulinastatin （UTI） on oxidative stress damage in rabbit brain tissues after cardiopulmonary resuscitation （CPR）. METHODS ： The model of cardiac arrest （CA） in adult male New Zealand rabbits was established and the levels of malondialdehyde （MDA） and glutathione （GSH） in plasma 24 h after restoration of spontaneous circulation （ROSC） were detected. In another experiment, 48 CA New Zealand rabbits were used. After ROSC, the animals were randomly divided into model group and UTI treatment group. The effects of UTI on MDA, GSH and the apoptosis of neurons in the cortex and hippocampus were observed. The effect of UTI on the expression of nuclear factor E2 - related factor 2 （Nrf2） was also analyzed. RESULTS： The concentration of MDA in plasma in- creased rapidly after CA and peaked at 2 h after ROSC, whereas the content of GSH dropped to a lower level. UTI restrained the rise of MDA in the cortex and hippocampus and increased the level of GSH. UTI also accelerated the activation of Nrf2. In the cortex and hippocampus CA1 - CA3 areas, the number of apoptotic neurons in model group was more than that in UTI group. CONCLUSION： UTI evidently increases the expression of Nrf2 in rabbit brain tissues, elevates the level of GSH and decreases the concentration of MDA to protect cortical and hippocampal neurons.