盐酸戊乙奎醚抑制JAK/STAT/NF-κB轴对急性一氧化碳中毒的脑保护作用及机制研究

Carbon monoxide (CO) poisoning is an acute occupational poisoning of the highest morbidity and mortality in China, the incidence of its most serious complication which named delayed encephalopathy after acute carbon monoxide poisoning (DEACMP). The mechanism of DEACMP has not been elucidated completely, some studies have shown that hypoxia-ischemia can cause a series of damaging effects of immune response, inflammation, oxygen free radical damage and etc. JAK/STAT/NF-κB pathway plays a key role in the immune and inflammatory response process, and is also participating in the process of cerebral ischemic injury. Our preliminary study has found that, penehyclidine hydrochloride can reduce the expression of NF-κB and TNF-α, and increased the expression of synaptophysin and IL-10 in rats of cerebral ischemia-reperfusion injury, and thus play a role of neuroprotection. Thus we speculate JAK/STAT/NF-κB pathway may play an important role in the pathogenesis of DEACMP. In our project, CO poisoning rat model, combining with morphological and molecular biology experiments are used to find out the role of JAK/STAT/NF-κB pathway and its associated inflammatory factors in DEACMP. This project will provide a new theoretical molecular mechanism of DEACMP, and potentially lead to a therapeutic breakthrough.

一氧化碳中毒是我国发病和死亡人数最多的急性职业中毒，一氧化碳中毒迟发性脑病（DEACMP）是其最严重的并发症，但其发生机制尚未彻底阐明，中毒后缺血缺氧可引起免疫反应、炎症反应、氧自由基损伤等一系列损伤效应。JAK/STAT/NF-κB轴在机体免疫与炎症反应过程中起着至关重要的作用，同时参与了脑缺血损伤所导致的炎症反应。本项目组前期研究发现，盐酸戊乙奎醚可以降低大鼠脑缺血再灌注损伤后脑组织中NF-κB、TNF-α的表达，并增加突触素和IL-10的表达，从而发挥脑保护作用。我们拟通过建立一氧化碳中毒大鼠模型，探索JAK/STAT/NF-κB轴及其相关的炎症因子在DEACMP发病中的作用，进一步研究盐酸戊乙奎醚在DEACMP发病中的脑保护作用。本课题将为DEACMP发生的分子生物学机制提供新的理论依据，有望为DEACMP提供新的治疗靶点。

一氧化碳中毒是我国发病和死亡人数最多的急性职业中毒，一氧化碳中毒迟发性脑病（DEACMP）是其最严重的并发症，中毒后缺血缺氧可引起免疫反应、炎症反应、氧自由基损伤等一系列损伤效应。JAK/STAT/NF-κB轴在机体免疫与炎症反应过程中起着至关重要的作用，同时参与了脑缺血损伤所导致的炎症反应。本项目组研究发现，JAK/STAT/NF-κB轴及其相关的炎症因子参与了DEACMP的发病，盐酸戊乙奎醚在DEACMP发病中具有脑保护作用。