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的影响

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。

Effects of artesunate on CD14 and toll-like receptor 4 in peritoneal macrophages of mice with heat stroke endotoxemia

OBJECTIVE: To study the effects of artesunate on CD14 and toll-like receptor 4 (TLR 4) expressions in peritoneal macrophages of mice with heat stroke endotoxemia. METHODS: Kunming mice were randomly divided 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 condition of dry bulb temperature (Tdb) 25 degrees C +/- 0.5 degrees C and relative humidity (RH) 43% +/- 5% for 2 hours, while other groups were exposed to the condition of Tdb 35 degrees C +/- 0.5 degrees C and RH 65% +/- 5%. The mRNA expressions of CD14 and TLR 4 in peritoneal macrophages and concentrations of tumor necrosis factor alpha (TNF alpha) in plasma were observed in different time points (1 hour and 2 hour). RESULTS: The mRNA 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 receptors 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-alpha in 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-alpha, which perhaps is one of the most important mechanisms that artesunate fights against endotoxemia.