【摘要】 目的探讨青蒿琥酯对中暑内毒素血症小鼠腹腔巨噬细胞内CD14和Toll样受体4 (TLR4)表达的影响。方法昆明种小鼠随机分为常温组、高温组、生理盐水组和青蒿琥酯组(均按60 mg/kg连续5 d腹腔注射),常温组在干球温度25℃±0．5℃、相对湿度43%±5%的条件下暴露2 h,其他组在干球温度35℃±0．5℃、相对湿度65%±5%的条件下热暴露,观察不同时间点(1、2 h)小鼠腹腔巨噬细胞内CD14和TLR 4 mRNA的表达及血浆中肿瘤坏死因子α(TNF-α)的含量。结果常温组CD14和TLR 4 mRNA表达分别为0．34%±0．047%和0．31%±0．062%；高温1 h组分别为0．53%±0．085%和0．45%±0．049%,与常温组的差异均有统计学意义(P＜0．01),并在2 h时呈现继续升高的趋势；生理盐水1 h组CD14和TLR4表达升高,但在2h时有轻度下降；青蒿琥酯1 h组CD14和TLR4的表达则分别为0．26%±0．051%和0．25%±0．084%,并在2 h有轻微的下降。各组TNF-α含量的变化呈现出与CD14、TLR 4变化基本一致的趋势。结论青蒿琥酯能明显降低内毒素信号转导通路上CD14和TLR 4的表达,减少TNF-α的产生,这可能是其抗中暑内毒素血症的机制之一。更多还原

【Abstract】 Objective To study the effects of artesunate on CD14 and toll-like receptor 4(TLR 4)expres- sions in peritoneal macrophages of mice with heat stroke endotoxemia.Methods Kunming mice were randomly di- vided into the normal temperature group,the hyperthermia group,the normal saline(NS) group and the artesunate group(both i.p.60 mg/kg daily for consecutive five days).The normal temperature group was exposed to the con- dition of dry btttb temperature(Tdb)25℃±0.5℃and relative humidity(RH)43%±5% for 2 hours,while oth- er groups were exposed to the condition of Tdb 35℃±0.5℃and RH 65%±5%.The mRNA expressions of CD14 and TLR 4 in peritoneal macrophages and concentrations of tumor necrosis factorα(TNFα)in plasma were observed in different time points(1 hour and 2 hour).Results The rnRNA expressions of CD14 and TLR 4 in the normal temperature group were 0.34%±0.047% and 0.31%±0.062% respectively.The expressions of two re- ceptors at 1 hour in the hyperthermia group were significantly increased to 0.53%±0.085% and 0.45%±0.049% compared with the normal group and kept increased at 2 hour(P＜0.01).The mRNA expressions at 1 hour in the NS group were significantly increased but a little bit decreased at 2 hour.The mRNA expressions of CD14 and TLR 4 at 1 hour in the artesunate group were 0.26%±0.051% and 0.25%±0.084% respectively and a little bit decreased at 2 hour.The change of TNF-αin each group was almost consistent with the changes of CD14 and TLR 4.Conclusion Artesunate can reduce significantly the expressions of CD14 and TLR 4 in LPS signal transduction pathway and the concentration of TNF-α,which perhaps is one of the most important mechanisms that artesunate fights against endotoxemia.更多还原