青蒿素对全身炎症反应综合征小鼠的保护作用  

Protective Effect of Artemisinin on Mice with Systemic Inflammatory Response Syndrome

作　　者：张红 杨庆[1] 孙立冬[1] 蔡维艳 李玉洁[1] 杨紫玉[1] 冉庆森 刘丽[1] 翁小刚[1] 李琦[1] 王娅杰[1] 朱晓新[1] 陈颖[1] ZHANG Hong;YANG Qing;SUN Li-dong;CAI Wei-yan;LI Yu-jie;YANG Zi-yu;RAN Qing-sen;LIU li;WENG Xiao-gang;LI Qi;WANG Ya-jie;ZHU Xiao-xin;CHEN Ying(Instinule of Chinese Materia Medica China Aeademy of Chinese Medical Sciences,Beijing 100700,China;Anhui University of Chinese Medicine.Hefei 230038,China)

机构地区：[1]中国中医科学院中药研究所,北京100700 [2]安徽中医药大学,合肥230038

出　　处：《中国实验方剂学杂志》2020年第15期20-25,共6页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家“重大新药创制”科技重大专项(2017ZX09101002-002-008,2017ZX09101002-002-002,2017ZX09101002-001-001-3);中国中医科学院十三五重点领域课题项目(2017ZZ10-024);载人航天工程航天医学实验领域项目(HYZHXM05003)。

摘　　要：目的:采用内毒素(LPS)所致全身炎症反应综合征(SIRS)小鼠模型,研究青蒿素对SIRS小鼠的保护作用及机制。方法:将5~7周龄的雄性BALB/c小鼠随机分为正常组,LPS模型组,青蒿素低、中、高剂量(25,50,100 mg·kg-1)组、布洛芬组(39 mg·kg-1),预防给药7 d后腹腔注射LPS(10 mg·kg-1)。根据SIRS临床诊断标准,检测小鼠的呼吸频率、肛温、白细胞分类、白细胞计数、血小板计数、肺指数、脾指数、糖脂代谢、脑组织炎症因子,以及肺组织炎症相关蛋白磷酸化情况。结果:与正常组比较,模型组腹腔注射LPS可使小鼠的呼吸频率明显降低(P<0.05),体温显著下降(P<0.01),脾指数显著升高(P<0.01),外周血中性粒细胞百分比明显增加(P<0.05),单核细胞百分比显著降低(P<0.01),血小板显著减少(P<0.01),血小板比积显著降低(P<0.01),血浆中总胆固醇含量显著降低(P<0.01),血浆葡萄糖含量显著降低(P<0.01),脑组织海马和皮层中白细胞介素-1β(IL-1β)分泌显著增多(P<0.01),脑组织海马、皮层中肿瘤坏死因子-α(TNF-α)分泌显著增多(P<0.01),肺组织磷酸化蛋白STAT1表达显著升高(P<0.01),磷酸化蛋白c-Jun表达显著升高(P<0.01);与模型组比较,青蒿素给药后,可显著升高LPS所致小鼠的体温和呼吸频率的降低,减轻LPS诱导的各脏器病理改变,可显著升高LPS所致的小鼠低血糖,可显著降低海马和皮层中炎性因子的水平,降低肺组织中磷酸化蛋白STAT1和c-Jun的表达(P<0.05,P<0.01)。结论:青蒿素可降低炎性因子TNF-α和IL-1β水平,对腹腔注射LPS致SIRS小鼠具有显著的保护作用。Objective:To study the protective effect and mechanism of artemisinin on systemic inflammatory response syndrome(SIRS)mice using endotoxin(LPS)-induced SIRS mouse model.Method:Male BALB/c mice aged 5-7 weeks were randomly divided into normal group,LPS model group,low,medium and high-dose artemisinin groups(25,50,100 mg·kg-1)and ibuprofen group(39 mg·kg-1).LPS(10 mg·kg-1)was intraperitoneally injected at the 7 thday after the prophylaxis.According to the SIRS clinical diagnostic criteria,the respiratory rate,rectal temperature,lung index,spleen index,glycolipid metabolism,brain tissue inflammatory factors,and phosphorylation of lung tissue inflammation-related proteins were measured.Result:Intraperitoneal injection of LPS significantly reduced the respiratory rate of mice(P<0.05),body temperature decreased significantly(P<0.01),spleen index increased significantly(P<0.01),peripheral blood neutrophil percentage increased significantly(P<0.05),percentage of monocytes decreased significantly(P<0.01),thrombocyte decreased(P<0.01),platelet specific ratio decreased(P<0.01),total cholesterol content in plasma decreased(P<0.01),plasma glucose content decreased(P<0.01).The expression of interleukin-1βincreased in hippocampus and cortex of brain tissue(P<0.01),and the secretion of tumor necrosis factor-αincreased in hippocampus and cortex of brain tissue(P<0.01).The expression of phosphorylated protein STAT1 was increased(P<0.01),and the expression of phosphorylated protein c-Jun was increased(P<0.01).After the administration of artemisinin,the body temperature and the respiratory rate of mice induced by LPS were significantly increased,the pathological changes of various organs induced by LPS were alleviated,the hypoglycemia induced by LPS was significantly increased(P<0.05),the levels of inflammatory factors in hippocampus and cortex was significantly reduced,and the expressions of phosphorylated proteins STAT1 and c-Jun in lung tissue were significantly reduced(P<0.05,P<0.01).Conclusion:Artemisinin has a significant

关 键 词：青蒿素 全身炎症反应综合征 炎性因子 

分 类 号：R2-0[医药卫生—中医学] R22