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吡喹酮与γ-干扰素对肝纤维化小鼠Smads转录水平的影响

Studies on Smads at transcription level in liver fibrosis of mice with schistosomiasis japonica after treatment with praziquantel and interferon-gamma
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摘要 [目的]研究吡喹酮杀虫治疗和γ-干扰素(IFN-γ)抗肝纤维化治疗对日本血吸虫性肝纤维化小鼠体内Smads分子的影响。[方法]日本血吸虫尾蚴感染BALB/c小鼠16周后形成肝纤维化动物模型,随机分成3组:0.85%氯化钠组、吡喹酮组和吡喹酮联合IFN-γ(联合)组,并以10只正常BALB/c小鼠作为正常对照。治疗8周后取小鼠肝组织,进行肝组织病理学检查,观察肝纤维化程度;应用RT-PCR法检测肝组织中Smad2、Smad3、Smad4、Smad7和IFN-γmRNA水平。[结果]吡喹酮组治疗后,肝纤维化程度、Smad2 mRNA水平与0.85%氯化钠组比较差异无统计学意义,Smad3 mRNA水平下降到正常,IFN-γmRNA水平明显增高。联合组治疗后,肝纤维化程度明显减轻,但尚未达到正常水平,Smad2 mRNA水平仍低于正常水平,Smad3和Smad7 mRNA水平上调,IFN-γmRNA处于正常水平。[结论]吡喹酮联合IFN-γ抗纤维化的机制是促进Smad7的表达,但Smad2 mRNA的下调,Smad3 mRNA的上调可能导致联合治疗未能使肝纤维化完全逆转。 [Objective]To study the Smads involved in TGF-βlsignaling transduction at the transcription level during the development of liver fibrosis and after treatment with praziquantel and interferon-gamma(IFN-γ)in the BALB/c mice infected by schistosoma japoncium. [Methods] BALB/c mice infected with cercariae of Schistosoma japonicum were used as liver fibrosis model. The infected mice were divided randomly into three groups at 16 week after saline :solution group,praziquantel group and praziquantel combined with IFN-γ group. Liver specimen were got at 8week post-infection. A part of liver specimen were preserved for pathologic examination and the other was frozen for the detection of the mRNA level of Smad2, Smad3, Smad4, Smad7 and IFN-γ. [Results] The degree of liver fibrosis did not improve after chemotherapy with praziquantel compared with the saline group. There was no difference of Smad2 mRNA between the group treated with praziquantel and the model group while the mRNA level of Smad3, Smad4 and Smad7 remained consistent with the normal. The level of IFN-γ mRNA increased after treatment with praziquantel. When praziquantel combined with IFN-γ,the degree of liver fibrosis improved significantly though it still remained higher compared with the normal mice. Smad2 mRNA was still in lower level. It was worth seeing that SmadTmRNA and Smad3 mRNA increased significantly. The mRNA level of Smad4 and IFN-Tremained consistent with the control group. [Conclusion ]The mechanism of anti-fibrosis of praziquantel combined with IFN-γ may increase the level of Smad7 while the reduction of smad2 mRNA and the increase of Smad3 mRNA may cause liver fibrosis not to resolve fully.
出处 《中国中西医结合消化杂志》 CAS 2008年第5期295-298,共4页 Chinese Journal of Integrated Traditional and Western Medicine on Digestion
关键词 日本血吸虫病 肝纤维化 吡喹酮 Γ-干扰素 SMAD Schistosomiasis japonica Liver fibrosis Praziquantel Interferon-γ Smad
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