摘要
目的探讨依达拉奉对急性-氧化碳（CO）中毒后脑组织损伤的神经保护作用及其作用机制。方法90只SD大鼠按随机数字表法分为正常组、中毒组和治疗组，每组30只。中毒组和治疗组大鼠应用高压氧舱法建立急性CO中毒模型并给予高压氧治疗，治疗组在此基础上给予腹腔注射依达拉奉（10mg／kg）。各组大鼠分别在中毒后1d、2d、7d应用TUNEL染色和RT-PCR法检测脑组织细胞凋亡情况及凋亡相关基因旧淋巴细胞瘤-2（Bcl-2）、Bax]mRNA表达，应用免疫组化染色和Westernblotting检测脑组织血红素加氧酶．1（HO—11和转录因子NF—E2相关因子2（NRF-2）阳性细胞及蛋白表达。结果与正常组比较，中毒组和治疗组凋亡细胞数明显增高，差异有统计学意义（p〈0．05）；与中毒组比较，治疗组凋亡细胞数相对减低，差异有统计学意义（P〈0．05）。中毒组Bcl-2mRNA和BaxmRNA表达水平较正常组明显升高．差异有统计学意义（P〈0．05）；与中毒组比较，治疗组Bcl-2mRNA表达水平明显增高，而BaxmRNA表达水平明显减低，Bcl-2mRNA／BaxmRNA的比值明显增高，差异有统计学意义（P〈0．05）。中毒组脑组织HO-1和NRF-2阳性细胞及蛋白表达水平明显高于正常组，治疗组脑组织HO-1和NRF-2阳性细胞及蛋白表达水平明显高于中毒组，差异均有统计学意义（P〈0．05）。结论依达拉奉可能通过参与NRF-2／HO-1途径激活对抗氧化应激损伤，抑制神经细胞凋亡，从而对急性CO中毒后脑损伤发挥神经保护作用。
Objective To evaluate the neuroprotective effect ofedaravone on brain tissues after acute carbon monoxide （CO） poisoning and explore its mechanism. Methods Ninety Sprague-Dawley rats were randomly selected as normal control group, poisoning group and treatment group （n=30）. Rats in the poisoning group and treatment group were established animal models of acute CO poisoning with hyperbaric chamber method and received hyperbaric oxygen therapy. The rats in the treatment group were given intraperitoneal injection ofedaravone （10 mg/kg） additionally. TUNEL and real time-PCR were used to detect the cell apoptosis and their apoptosis-related gene expressions （Bcl-2 and Bax mRNA） in brain tissues l, 2 and 7 d after CO poisoning in each group. Immunohistochemistry and Western blotting were used to observe the positive cells and protein changes of heine oxygenase-1 （HO-1） and nuclear factor erythrocyte two related factors-2 （NRF-2）. Results The apoptosis cell number in the poisoning group and the treatment group was significantly increased as compared with that in the normal control group （P〈0.05）; that in the treatment group was relatively fewer than that in the poisoning group with significant differences （P〈0.05）. As compared with those in the normal control group, the Bcl-2 and Bax mRNA expressions in the poisoning group were obviously up-regulated with significant difference （P〈0.05）; the Bcl-2 mRNA level was significantly increased, the Bax mRNA levelwas signficantly down-regulated, and the ratio of Bcl-2 mRNA/Bax mRNA was notablyly increased in the treatment group as compared with those in the poisoning group （P〈0.05）. The positive cells and HO-1 and NRF-2 proteins in the brain tissues of the poisoning group were significantly higher than those in the normal group （P〈0.05）; those in the treatment group were obviously increased as compared with those in the poisoning group （P〈0.05）. Conclusion Edaravone might be partly associated with activation of NRF-2/HO-1 pathway to counteract oxidative stress damage, inhibit neuronal apoptosis, and play a neuroprotective role in brain damage after acute CO poisoning.
出处
《中华神经医学杂志》
CAS
CSCD
北大核心
2015年第8期810-816,共7页
Chinese Journal of Neuromedicine
作者简介
通信作者：毕明俊，Email：bimingjun00@163．com
