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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。
Objective To investigate the effect of artesunate on the expression of CD14 and Toll-like receptor 4 (TLR4) in peritoneal macrophages of mice with heat stroke endotoxemia. Methods Kunming mice were randomly divided into two groups: normal temperature group, high temperature group, normal saline group, and artesunate group (all 60 mg/kg consecutively for 5 d intraperitoneally). The normal temperature group was at a dry bulb temperature of 25°C±0.5°C. , Exposure to relative humidity of 43% ± 5% for 2 hours, other groups exposed to dry bulb at 35°C ± 0.5°C, relative humidity 65% ± 5%, observed at different time points (1, 2) h) Expression of CD14 and TLR4 mRNA in mouse peritoneal macrophages and plasma tumor necrosis factor alpha (TNF-α) content. Results The expression of CD14 and TLR4 mRNA in the normothermia group was 0.34%±0.047% and 0.31%±0.062%, respectively; in the high temperature 1 h group, they were 0.53%±0.085% and 0.45 respectively. %±0.049%, and the difference between the normal temperature group and the normal temperature group were statistically significant (P<0.01), and showed a tendency to continue to increase at 2 h; the expression of CD14 and TLR4 was increased in the normal saline group for 1 h, but There was a slight decrease at 2 h; the expression of CD14 and TLR4 in artesunate 1 h group was 0.26%±0.051% and 0.25%±0.084%, respectively, and there was slight at 2 h. decline. The changes of TNF-α content in each group showed a trend consistent with the changes of CD14 and TLR4. Conclusion Artesunate can significantly reduce the expression of CD14 and TLR4 on the endotoxin signal transduction pathway and reduce the production of TNF-α, which may be one of the mechanisms of its resistance to heat stroke endotoxemia.