青蒿琥酯抗中暑内毒素血症的机制研究

Study on mechanism of artesunate against endotoxemia of heat stroke

目的探讨青蒿衍生物青蒿琥酯抗中暑内毒素血症的作用机制,为该类药物应用于重症中暑的治疗提供依据。方法在干球温度(34.5±0.5)℃,相对湿度(60±5)%的条件下建立小鼠中暑内毒素血症模型,将32只小鼠随机分为青蒿琥酯组、高温对照组、生理盐水组和正常对照组。用ELISA法检测血浆肿瘤坏死因子-a(TNF-a)含量变化,RT-PCR检测腹腔巨噬细胞Toll样受体4(TLR4)mRNA表达情况。结果青蒿琥酯组TNF-a的含量和TLR4mRNA表达低于高温对照组和生理盐水组(P<0.05),与正常对照组相近。结论下调内毒素信号转导通路中TLR4mRNA表达,减少TNF-a的含量,应是青蒿琥酯拮抗中暑内毒素血症的重要机制之一。

Objective To investigate the mechanism that artesunate against endotoxemia of heat stroke and provide experimental evidence for application of this kind of medicine in the treatment of heat stroke. Methods Establishing the heat stroke model under circum stances of dry bulb temperature （34.5 ± 0.5） %3 and （60 ± 5） % relative humidity, 32 mice were randomly divide into four groups including artesnate group, heat stroke group, shengliyanshui group and normal group, tumor necrosis factor （TNF-a） of blood using reagent case and TLR4 mRNA ofperitoneal macrophage using RT-PCR in mice wee observed. Results The quantity of TNF-a and the expression of TLR4 mRNA of artesunate group were lower significantly （P 〈 0.05） than those of heat stroke group and shengliyanshui group but similar to normal group. Conclusion One of the most important mechanism that artesunate against endotoxemia of heat stroke is decrease the quantity of TNF-a by downing regulation the expression of TLR4, which is the essential factor of lipopolysaccharide （LPS） signal transduction pathway.