青蒿琥酯对热灭活金黄色葡萄球菌攻击小鼠的保护作用

目的明确青蒿琥酯（artesunate，AS）对热灭活金黄色葡萄球菌（staphylococcus aureus，SA）攻击小鼠的保护作用，以及对亚致死剂量热灭活SA攻击小鼠血清释放细胞因子TNF-α的影响。方法尾静脉注射LD。剂量的热灭活SA攻击小鼠，于注射热灭活SA后0、4、24、48h重复肌肉注射AS，观察给药后7d内小鼠的死亡率；尾静脉注射亚致死剂量热灭活SA，肌肉注射AS，4h后眼眶取血，离心取上清，观察AS对亚致死剂量热灭活SA攻击小鼠血清释放TNF-α的影响。结果AS可明显推迟热灭活SA攻击小鼠的死亡时间，并降低小鼠死亡率，死亡率由80％降低至40％（P〈0．01）；AS能明显抑制亚致死剂量热灭活SA攻击小鼠血清释放细胞因子TNF—α，并呈明显量效关系（P〈0．01）。结论AS对热灭活SA攻击小鼠具有显著保护作用，该保护作用可能与其明显抑制促炎细胞因子释放有关。

The Protective Effect of Artesunate on Mice Challenged with Heat-killed Staphylococcus Aureus

Aim To observe the protective effect of artesunate （AS） on mice challenged with heat-killed Staphylococcus aureus （SA） and its inhibition on the release of cytokines induced by heat-killed SA. Methods A total of 120 mice of Kunming were randomly divided into six groups. The AS group received heat-killed SA only at 1.6 × 10^12CFU/kg. The AS group received artesunate at 30mg·kg^-1 by intramuscular injection. AS plus SA groups first received AS （7.5,15,30mg·kg^-1 ）, then heat-killed SA at the same dose. AS was repeated injected intramuscully at the 0,4,24h and 48h after heat-killed SA challenge, and the control group received only saline（NS） . The mortality was observed within seven days after injection via the caudal vein. At 4h after injection, blood samples were collected from 10 mice in each group for cytokine assay. The cytokine TNF-α level was assayed using mouse ELISA kits. Results Artesunate delayed the toll time and decreased the death number of mice challenged with heat-killed SA, and the mortality decreased from 80% to 40% （ P 〈 0. 01 ）. AS could significantly inhibit the release of TNF- α in mice challenged with heat-killed SA at a sublethal dose in a dose-dependent manner. （ P 〈 0.01）. Conclusion Artesunate coned well protect mice challenged by heat-killed SA, and remarkably inhibit the release of cytokines induced by heat-killed SA, suggesting that artesunate might be an effective drug for sepsis.