【摘要】 目的　探讨吡喹酮杀虫治疗和IFN γ抗肝纤维化的分子机制。方法　以日本血吸虫尾蚴感染新西兰兔制成肝纤维化动物模型 ,感染后第 16周随机分成 3组 :感染组 ,吡喹酮治疗组和吡喹酮联合IFN γ治疗组 ,另以 10只正常兔为阴性对照组。感染后 2 8周处死 ,取肝组织进行病理学检查以及Ⅰ型胶原、Ⅲ型胶原、Ⅳ型胶原、MMP 1、MMP 9、TGFβ1和IFN γmRNA水平检测。结果　吡喹酮治疗后肝纤维化程度明显减轻 ,但仍显著高于正常组 ;Ⅰ型胶原、Ⅲ型胶原和Ⅳ型胶原mRNA水平显著下降 ,尤其Ⅲ型胶原已接近正常水平 ,而MMP 1和MMP 9mRNA水平变化不大 ;TGFβ1mRNA水平下降不明显 ,而IFN γmRNA水平显著增高 ,TGFβ1/IFN γmRNA比值明显减小 ,但仍高于正常。杀虫治疗后加IFN γ可进一步降低Ⅰ型胶原、Ⅳ型胶原mRNA水平 ,并使MMP 1和MMP 9mRNA的表达显著增加 ,TGFβ1mRNA水平明显下降。结论　杀虫治疗后抗肝纤维化仍属必要 ,IFN γ主要通过直接抑制胶原合成 ,促进胶原降解 ,抑制TGFβ1起抗肝纤维化作用。更多还原

【Abstract】 Objective To explore the molecular mechanism of praziquantel and IFN γ in the treatment of liver fibrosis. Methods New Zealand rabbits challenged by cercariae of Schistosoma japonicum were used as liver fibrotic model. Three groups were divided at sixteen weeks after the challenge: praziquantel treatment group, praziquantel combined with IFN γ treatment group and saline treatment group. Ten other rabbits were used as normal control. All rabbits were sacrificed at twenty eight weeks after the challenge. A part of liver specimen was preserved for pathological examination, and the other was frozen for detecting the mRNA level of type Ⅰ collagen, type Ⅲ collagen, type Ⅳ collagen, MMP 1, MMP 9, TGF β 1 and IFN γ. Results The degree of liver fibrosis, which was still significantly higher than the normal control decreased sharply 12 weeks after the treatment with praziquantel. TypeⅠ, Ⅲ, Ⅳ collagen mRNA level also decreased, and especially type Ⅲ collagen was almost near normal level, while MMP 1 and MMP 9, mRNA level did not show significant change. TGF β 1 mRNA level decreased slightly, while IFN γ mRNA level increased significantly, and thus led to the significant decrease of ratio of TGF β 1 and IFN γ mRNA level. When praziquantel treatment combined with IFN γ, the mRNA level of type Ⅰ, Ⅳ collagen decreased and MMP 1 and MMP 9 mRNA level increased significantly. TGF β 1 mRNA level decreased significantly. Conclusions Anti fibrotic treatment is necessary after the treatment of praziquantel. The anti fibrotic effect of IFN γ is based on reducing synthesis and enhancing degradation of collagen and inhibiting the secretion of TGF β 1.更多还原