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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 被引量:5

Investigation on the role of praziquantel against Schistosoma japonicum induced liver fibrosis and expression change of host miRNA
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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3 d进行杀虫。再以600mg/(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、milt-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。 Objective To investigate the role and mechanism of praziquantel against Schistosomajapon-icum egg induced liver fibrosis. Methods BALB/c mice were infected with Schistosomajaponicum as ex-perimental mouse model. In the experimental group, praziquantel at 250 mg/(kg.d) for consecutive 3 days asinsecticide treatment and at 600 mg/(kg .d) for 30 days of continuous administration as antifibrotic therapywhile in the control group, the mice only given praziquantel insecticide treatment. The extent of liver fibrosiswas evaluated by detection on liver hydroxyproline content and other indicators , and by detection on certainmicro RNA (microRNA, miRNA) expression levels in liver tissues with real-time quantitative PCR(real-timePCR). Test results of each group were statistically analyzed with t test. Results liver hydroxyproline con-tent of hepatic fibrosis was significantly reduced due to praziquantel treatment. Liver hydroxyproline contentin 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 theinfection group and insecticide group(t=12.86, P〈0.01 ). While some significant changes in miRNA expressionlevels of mouse liver exhibited in the treatment group compared with that in the insecticide group such as thedown-regulation of Col I by 62%, miR-223 by 38%, miR-146b by 75%, miR-142- 5p by 77%, miR-199a-Spby 40%, miR-34c by 54%, and miR-195 by 56%. Conclusion Praziquantel may have certain therapeuticeffects on schistosomiasis japonica liver fibrosis by modulating the expression of certain host miRNA expres-sion levels. [
出处 《国际医学寄生虫病杂志》 CAS 2015年第1期1-5,13,共6页 International JOurnal of Medical Parasitic Diseases
基金 国家科技重大专项(2012ZX10004220)~~
关键词 日本血吸虫 吡喹酮 肝纤维化 微小RNA Schistosomajaponicum Praziquantel Liver fibrosis MicroRNA
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