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γ干扰素治疗对日本血吸虫病肝纤维化小鼠转化生长因子β1及其受体的影响 被引量:9

Influence of Interferon γ Treatment on Expression of TGF-β1 and Its Receptors in Liver Fibrosis of Mice with Schistosomiasis japonica
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摘要 目的 γ干扰素 (IFN γ)治疗日本血吸虫病肝纤维化小鼠 ,观察小鼠肝组织转化生长因子 β1(TGF β1)及其I、II型跨膜受体 (TβRI、TβRII)表达的变化 ,同时动态观察日本血吸虫病小鼠肝纤维化形成过程中TGF β1、TβRI及TβRII的变化趋势。 方法 日本血吸虫尾蚴感染BALB/c小鼠 ,16周后随机分为模型组、吡喹酮治疗组和吡喹酮联合IFN γ治疗组 ,治疗 8周。于感染后 8、12、16周和疗程结束后进行肝组织病理学检查 ;免疫组织化学法检测TGF β1、TβRI及TβRII表达部位 ;逆转录 聚合酶链反应 (RT PCR)检测小鼠肝组织TGF β1、TβRI及TβRII转录水平。  结果 TGF β1、TβRI和TβRII在小鼠肝细胞、窦周细胞中均有表达 ,随感染时间的延长 ,表达增强 ,特别在虫卵肉芽肿周围 ;IFN γ治疗后 ,虫卵肉芽肿减少 ,TGF β1、TβRI及TβRII表达较治疗前降低 ;TGF β1mRNA在感染后 12周表达开始上调 ,模型组达高峰 (P <0 .0 5 ) ,经吡喹酮联合IFN γ治疗后降至正常水平 ;TβRIImRNA在感染后 8、16周表达下调 (P <0 .0 5 ) ,疗程结束后恢复正常 ;TβRImRNA表达水平在发病和治疗过程中均无明显变化。  结论 TGF β1表达上调和TβRIImRNA表达下调促进肝纤维化形成 ,IFN γ抑制TGF β1的分泌的机制可能是通过下调TGF ? Objective To investigate the effect of interferon -γ(IFN-γ)on the expression of TGF-β1 and its two membrane receptors - TGF-β receptor I (TβRI), TGF-β receptor II (TβRII), and observe the expression of TGF-β1, TβRI and TβRII during the development of liver fibrosis in BALB/c mice infected by Schistosoma japonicum. Methods BALB/c mice, aged 6-8 weeks, were infected with cercariae of S. japonicum. The infected mice were divided randomly into three groups 16 week after infection:model group,praziquantel group and praziquantel combined with IFN-γ group. Liver specimen were obtained at 8, 12, 16 week and at the end of treatment. Pathological examination, immunohistochemistry and RT-PCR were used to evaluate the pathological change, the expression of TGFβ1, TβRI and TβRII and the mRNA level respectively. Results The expression of TGF-β1, TβRI, and TβRII can be detected in infected mice, while the expression around egg granulomas enhanced along with the progress of the disease. With the therapy of IFN-γ, the reduction of egg granulomas, and of the expression of TGF-β1, TβRI and TβRII was observed. From the transcription level, it was found that TGF-β1 mRNA increased at 12 week and peaked at model group, then decreased to the normal level after treatment with IFN-γ combined with praziquantel. The level of TβRII mRNA reduced at 8 and 16 week and returned to normal at the end of treatment. More interestingly, TβRI mRNA remained at the normal level on the whole course both in the development of fibrogenesis and the period of treatment. Conclusion The up regulation of TGFβ1 and down regulation of TβRII mRNA may induce liver fibrogenesis and IFN-γ might suppress TGFβ1 to reverse fibrosis. The mechanism of the suppression is mediated by down regulation of expression of its two receptors at protein level but not by influencing the mRNA expression.
出处 《中国寄生虫学与寄生虫病杂志》 CAS CSCD 北大核心 2004年第6期340-343,i002,共5页 Chinese Journal of Parasitology and Parasitic Diseases
关键词 TβRⅡ 表达 治疗 TGF—β1 小鼠 鼠肝 IFN-γ 疗程 感染时间 转化 Schistosomiasis japonica Liver fibrosis Transforming growth factor-β1 Receptor Therapy
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