青蒿琥酯抗小鼠血吸虫性肝纤维化的作用  

Effects of artesunate on schistosomal liver fibrosis in mice

作　　者：孔庆明[1] 戴方伟[2] 丁豪杰 郑清四 卢领群[2] 卓洵辉 楼琦[2] 楼涤[1] 郑斌[1] 丁建祖[1] 褚晓峰 陆绍红[1] KONG Qing-ming;DAI Fang-wei;DING Hao-jie;ZHENG Qing-si;LU Ling-qun;ZHUO Xun-hui;LOU Qi;LOU Di;ZHENG Bin;DING Jian-zu;CHU Xiao-feng;LU Shao-hong(Institute of Parasitic Disease;Laboratory Animal Center,Zhejiang Academy of Medical Sciences,Hangzhou 310013,China;Guilin Pharmaceutical (Shanghai) Co., Ltd., Guilin, Guangxi 541004, China;Zhejiang Public Service Platform for Experimental Animals, Hangzhou 310013, China)

机构地区：[1]浙江省医学科学院寄生虫病研究所 [2]浙江省实验动物中心,浙江杭州310013 [3]桂林南药股份有限公司,广西桂林541004 [4]浙江省实验动物公共服务平台,浙江杭州310013

出　　处：《中国药理学通报》2019年第6期854-858,共5页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 31501050);浙江省医药卫生科技计划资助项目(No 2015KYA059);浙江省科技计划项目(No 2017C37184;LQY19H190002);杭州市重大科技创新项目(No 20142013A62)

摘　　要：目的研究青蒿琥酯(artesunate,ART)体内抗血吸虫性肝纤维化的作用,探讨其分子机制。方法小鼠经腹部贴片感染血吸虫尾蚴建立肝纤维化动物模型,16周开始每天给予ART灌胃治疗,连续8周。停药4周后,通过定量PCR与Western blot,检测小鼠肝组织内纤维化形成相关基因与CHI3L1/ERK信号通路基因的表达水平。结果成功建立了血吸虫性肝纤维化小鼠模型。病理学指标评分显示,ART治疗血吸虫性小鼠肝纤维化有效。给药后,小鼠肝脏基质金属蛋白酶抑制因子TIMP-1和Ⅲ型胶原蛋白Col3α1基因表达水平明显降低,壳多糖酶3样蛋白CHI3L1和ERK1/2基因表达量的降低也具有统计学意义,ERK磷酸化水平被明显抑制。结论 ART在体内对血吸虫性肝纤维化具有明显的抑制作用,其机制可能与抑制胶原蛋白合成及CHI3L1/ERK信号通路的传导有关。Aim To study the role and the molecular mechanism of artesunate in anti-schistosomal liver fibrosis in vivo . Methods Mouse model of liver fibrosis due to Schistosoma japonica infection was established by placing the coverglass with cercaria on the hairless belly. Mice were started on a 8-week regimen of artesunate (ART) daily in 16th week post infection. Mice were observed for four weeks after ART treatment course. The expression of fibrosis genes and CHI3L1/ERK pathway related genes were detected by quantitative PCR and Western blot. Results Mouse model of schistosomal liver fibrosis was established successfully. Evidence of pathological changes was found for effectiveness of artesunate in the treatment of schistosomal liver fibrosis. The expression of tissue inhibitors of metaslloproteinases 1 (TIMP1) and type Ⅲ collagen of mice in treatment group were significantly reduced compared those of model group. The CHI3L1 and ERK1/2 gene expression level of mice in treatment group decreased significantly compared to that of model group. The phosphorylation level of ERK was also significantly inhibited. Conclusions ART suppresses liver fibrosis of schistosomiasis japonica in vivo and the mechanism for the liver protective effect is related to the inhibition of collagen production and the transmission of CHI3L1/ERK pathway.

关 键 词：青蒿琥酯 血吸虫 肝纤维化 壳多糖酶3样蛋白1 胶原蛋白 细胞外调节蛋白激酶 

分 类 号：R-332[医药卫生] R284.1