吡喹酮对日本血吸虫病肝纤维化的治疗作用及宿主miRNA表达变化
Investigation on the role of praziquantel against Schistosoma japonicum induced liver fibrosis and expression change of host miRNA
陈超 1白瑞璞 1何兴 1潘卫庆1
作者信息
- 1. 200433上海,第二军医大学热卫系热带传染病病学教研室
- 折叠
摘要
目的 研究吡喹酮对日本血吸虫虫卵引起的肝纤维化的治疗作用及其可能的机制. 方法 选用BALB/c小鼠建立日本血吸虫感染小鼠模型,实验组以250 mg/(kg·d)吡喹酮连续用药3d进行杀虫,再以600 mg/(kg·d)连续给药30 d进行抗纤维化治疗;对照组仅进行吡喹酮杀虫.以肝组织羟脯氨酸含量等指标评定小鼠肝纤维化的程度,并通过实时荧光定量PCR (real-time PCR)检测各组肝组织中某些微小RNA (microRNA,miRNA)的表达水平.各组检测结果以t检验进行统计学分析.结果 经过吡喹酮治疗后,小鼠肝脏羟脯氨酸含量等肝纤维化指标明显降低,小鼠肝脏羟脯氨酸含量:感染后第75天,感染组、杀虫组、治疗组依次为(0.86±0.07)、(0.66±0.06)、(0.25±0.05) mg/g肝湿重,治疗组低于感染组和杀虫组(t=12.86,P＜0.01).同时小鼠肝脏的部分miRNA表达水平发生了明显改变,治疗组与杀虫组相比较,Col I、miR-223、miR-146b、miR-142-5p、miR-199a-5p、miR-34c*、miR-195依次下调了62％、38％、75％、77％、40％、54％和56％. 结论 吡喹酮对日本血吸虫病肝纤维化有一定的治疗作用,其作用可能与调节某些宿主miRNA的表达水平有关.
Abstract
Objective To investigate the role and mechanism of praziquantel against Schistosoma japonicum egg induced liver fibrosis.Methods BALB/c mice were infected with Schistosoma japonicum as experimental mouse model.In the experimental group,praziquantel at 250 mg/(kg·d) for consecutive 3 days as insecticide treatment and at 600 mg/(kg·d) for 30 days of continuous administration as antifibrotic therapy while in the control group,the mice only given praziquantel insecticide treatment.The extent of liver fibrosis was evaluated by detection on liver hydroxyproline content and other indicators,and by detection on certain micro RNA (microRNA,miRNA) expression levels in liver tissues with real-time quantitative PC R (real-time PCR).Test results of each group were statistically analyzed with t test.Results liver hydroxyproline content of hepatic fibrosis was significantly reduced due to praziquantel treatment.Liver hydroxyproline content in D75 infection group,insecticide group and treatment group were (0.86±0.07),(0.66±0.06) and (0.25±0.05) mg/g liver wet weight respectively,the hydroxyproline content in the treatment group is lower than that in the infection group and insecticide group(t=12.86,P＜0.01).While some significant changes in miRNA expression levels of mouse liver exhibited in the treatment group compared with that in the insecticide group such as the down-regulation of Col I by 62％,miR-223 by 38％,miR-146b by 75％,miR-142-5p by 77％,miR-199a-5p by 40％,miR-34c* by 54％,and miR-195 by 56％.Conclusion Praziquantel may have certain therapeutic effects on schistosomiasis japonica liver fibrosis by modulating the expression of certain host miRNA expression levels.
关键词
日本血吸虫/吡喹酮/肝纤维化/微小RNAKey words
Schistosoma japonicum/Praziquantel/Liver fibrosis/MicroRNA引用本文复制引用
基金项目
国家科技重大专项(2012ZX10004220)
出版年
2015
NETL
NSTL
维普
万方数据