丁苯酞对急性一氧化碳中毒大鼠脑组织Nogo／NgR表达的调节作用

N-Butylphthalide downregulates Nogo/NgR expressions in rat brain tissues after carbon monoxide poisoning

目的探讨轴突生长抑制蛋白（Nogo）、髓磷脂相关糖蛋白（MAG）及其共受体Nogo受体1（NgR1）在急性一氧化碳（CO）中毒大鼠脑组织中的表达，以及丁苯酞（NBP）对CO中毒的神经保护作用。方法60只SD大鼠按随机数字表法分为正常对照组、CO中毒组和NBP治疗组．每组各20只。CO中毒组和NBP治疗组大鼠用高压氧舱法建立急性CO中毒模型并给予高压氧治疗，NBP治疗组大鼠在此基础上给予NBP（6mg／100g）灌胃。分别在中毒后1d、3d、1周、4周（每组每时间点取5只大鼠），应用免疫组化染色及免疫荧光染色双标法观察各组大鼠脑组织Nogo、MAG及NgR1的表达变化。结果随着中毒后病程的延长，CO中毒组大鼠脑组织Nogo、MAG及NgR1表达亦逐渐增加，在中毒后4周仍可观察到。给予NBP治疗能明显降低大鼠脑组织Nogo及NgR1蛋白的表达，其水平与CO中毒组相应时间点比较差异均有统计学意义（P〈0．05）；NBP治疗组大鼠脑组织MAG表达水平较CO中毒组相应时间点略有升高，但差异无统计学意义（P〉0．05）。结论CO中毒后脑损伤及脑组织脱髓鞘改变可能与CO诱导Nogo、MAG及NgR1蛋白表达改变有关。NBP能明显下调Nogo及NgR1（而不是MAG）的表达水平，从而对CO中毒后脑损伤有积极的保护作用。

Objective To investigate the expressions of neurite outgrowth inhibitor （Nogo）, myelin-associated glycoprotein （MAG） and Nogo receptor-1 （NgR1）, and neuro-protective effect of N-Butylphthalide （NBP） in rat brain tissues following acute CO poisoning. Methods Sixty Sprague-Dawley rats were randomly divided into normal group, CO poisoning group and NBP treatment group （n=20）. Rats in CO poisoning group and NBP treatment group were induced acute CO poisoning in hyperbaric chamber and received hyperbaric oxygen therapy. Meanwhile, rats in the NBP treatment group were subjected to oral NBP 6 mg/100 g twice a day additionally. The expressions of Nogo, MAG and NgR1 were investigated in rat brain tissues by immunohistochemistry and double immunofluorescence staining 1 day, 3 days, 1 week and 4 weeks after CO exposure. Results With the prolongation of CO poisoning, the levels ofNogo, MAG and NgR1 in brain tissues of the CO poisoning group were gradually increased, and their expressions could still be detected at 4 weeks after CO poisoning. NBP treatment group had significantly reduced Nogo and NgR1 protein levels, and statistical differences were noted as compared with those in the CO poisoning group at each time point （P〈0.05）. The level of MAG in NBP treatment group was slightly lower than that in CO poisoning group without statistical difference （P〉 0.05）. Conclusions The levels ofNogo, MAG and NGR1 proteins may be associated with brain injury and demyelination induced by CO poisoning. NBP can downregulate the levels of Nogo and NgR1 proteins （but not MAG）, and may play a neuro-protective role in brain damage after acute CO poisoning.