基于p38信号通路的井穴放血法对急性一氧化碳中毒的脑保护作用机制研究

Acute carbon monoxide poisoning (ACOP) ranks the top from the aspects of both the rates of occurrence and mortality of poisoning. The urgent problem is to explore an approach, which is efficient, effective and economical, for the treatment at early stage. The pathogenesis of ACOP mainly includes that of hypoxia and that of post-hypoxia inflammatory reaction. When the triggering factor in inflammation -blood hypoxia is removed, inflammation still exists. Besides, the degree of inflammatory reaction at the early stage corresponds with the severity of brain damage. The p38 signaling pathway is an important signal pathway to regulate inflammatory media. Bloodletting at Jing-points is a traditional measure of Chinese medicine for first aid.Based on the effectiveness which was tested by the clinical treatment of ACOP with the aid of bloodletting on Jing-points. This study ,taking the p38 signaling pathway in the inflammatory reaction as the starting point ,will establish the ACOP rat model to observe the effects of bloodletting at Jing-points on the downstream signaling molecules of the p38 signaling pathway in the ACOP rat models,explore the mechanism of bloodletting at Jing-pointson on the effect of brain protection and provide the experimental foundation to interpret this medical treatment by the means of integrated techniques and ways of Immunology and Molecular Biology and so on.

急性一氧化碳中毒（ACOP）是当今发生率和死亡率最高的中毒。寻求及时、有效、经济的早期治疗方法是急待解决的问题。ACOP发病机制主要包括缺氧机制和缺氧后的炎症反应机制，而在炎症的始动因素--血液性缺氧被解除后，炎症继续存在，且早期炎症反应程度与脑损伤程度相关，p38信号通路是调节炎症介质的重要信号通路。井穴放血法为中医传统的急救措施，在我们前期临床配合应用井穴放血干预ACOP有效的基础上，本研究通过建立ACOP大鼠模型，以炎性反应中的p38信号通路为切入点，综合运用免疫学、分子生物学等技术方法观察井穴放血法对ACOP大鼠模型p38信号通路下游信号分子的影响，探索井穴放血法的脑保护机制，为该法作用机理的阐释提供实验依据。

急性一氧化碳中毒（ACOP）机制复杂，由此引起的迟发性脑病机制尚不完全明确。近年来关于炎症机制在 CO 中毒中作用的研究日益增多，本研究从调节炎症介质的信号转导通路入手，以井穴刺络放血法对p38MAPK信号传导通路的调节为切入点，开展了井穴放血法对ACOP的脑保护作用机制研究。. 在大鼠ACOP模型成功建立的基础上，给予井穴刺络放血处理后，从行为学角度直接证明了井穴放血法可以减轻CO中毒所致的大鼠学习和记忆能力下降，从形态学角度证明了井穴放血法可以降低CO中毒大鼠脑组织海马CA1区神经元损伤，初步建立了井穴放血治疗ACOP大鼠实验研究平台，初步肯定了井穴放血法对ACOP大鼠的脑保护作用。. 以此平台为基础开展研究，发现了井穴放血法可显著抑制p38MAPK 信号通路下游转录因子的活化，下调促炎因子的表达，证明了井穴放血对 ACOP 大鼠脑组织 p38MAPK 信号通路下游转录因子及促炎细胞因子表达的影响；发现了井穴放血法可显著抑制（p-p38MAPK /p38MAPK）磷酸化水平表达，证明了井穴放血法对 ACOP 大鼠脑组织p38MAPK磷酸化水平表达的影响。结合前期大量研究成果，证明了井穴放血法对ACOP大鼠脑组织炎症反应的信号调控通路p38MAPK的调节作用，初步阐释了井穴放血法对ACOP大鼠的脑保护作用的部分机理，为中医针灸疗法应用于 ACOP 的救治提供可靠实验依据。