吡非尼酮对实验性大鼠肝纤维化的作用

山东大学学报(医学版) ›› 2009, Vol. 47 ›› Issue (11): 50-54.

吡非尼酮对实验性大鼠肝纤维化的作用

杜磊，王昌源，张立华，谭炳芹

山东大学医学院济南市传染病医院，济南 250021

收稿日期:2008-12-21 发布日期:2009-11-16
通讯作者: 王昌源（1961- ），男，博士，教授，主要从事肝脏病研究。Email: wangcy5440@163.com
作者简介:杜磊（1982- ），女，硕士研究生，主要从事肝脏病研究。

Effects of pirfenidone on liver fibrosis in rats

DU Lei, WANG Changyuan, ZHANG Lihua, TAN Bingqin

Jinan Infectious Disease Hospital, School of Medicine, Shandong University, Jinan 250021, China

Received:2008-12-21 Published:2009-11-16

摘要/Abstract

摘要：

目的研究吡非尼酮（PFD）对实验性大鼠的抗肝纤维化作用。方法45只雄性Wistar大鼠随机均分为3组。模型组腹腔注射1%二甲基亚硝胺（DMN）10?mg/(kg·d)，每周连续3d，共4周，制作肝纤维化模型；干预组除应用DMN外，同时给予PFD 500?mg/(kg·d)灌胃，1次/d，共4周；模型组及正常组以等体积生理盐水灌胃作对照。4周试验结束时进行组织学检查、电镜观察、血清肝纤维化指标、肝功能及转化生长因子β1（TGFβ1）检测。结果与模型组相比，干预组大鼠体质量下降较少(P＜0.05)、肝脾肿大较轻（P＜0.05），血清透明质酸、层粘连蛋白和Ⅳ型胶原浓度均明显低于模型组（P＜0.05）；干预组血清谷丙转氨酶、谷草转氨酶、总胆红素及TGFβ1含量与模型组相比明显降低（P＜0.001）；MASSON染色显示，干预组肝脏纤维化及炎症反应明显减轻，无明显假小叶；透射电镜观察证实干预组大鼠肝细胞损伤明显减轻，肝窦及Disse腔内胶原纤维沉积明显减少。结论PFD对实验性大鼠肝纤维化模型具有明显的抗肝纤维化作用，其机制可能与抑制TGFβ1的产生有关，PFD有可能用于肝脏疾病的抗纤维化治疗。

关键词: 吡非尼酮；纤维化，肝；大鼠，Wistar；转化生长因子β1

Abstract:

To investigate the effects of pirfenidone (PFD) on liver fibrosis in experimental rats. MethodsFortyfive male Wistar rats were randomly divided into three groups. The model group was intraperitoneally injected with 1% dimethylnitrosamine (DMN) 10?mg/kg per day for the first three days of each week for 4 weeks. The intervention group was orally given PFD 500?mg/kg every day for 4 weeks starting on the day of the first injection of DMN. The control group was given normal sodium. Rats were killed at the end of the 4th week, and the livers and spleens were removed. Blood samples were obtained immediately before rats were killed. Liver histological and ultramicroscopic changes were observed, serum indices of liver fibrosis and liver function were examined, and the level of transforming growth factor β1 (TGFβ1) was determined. ResultsCompared with the model group, the intervention group had a higher bodyweight(P＜0.05) but splenohepatomegalia was less(P＜0.05). Serum levels of hyaluronic acid, laminin and type Ⅳ collagen of the intervention group were significantly lower than those of the model group(P＜0.05), however serum levels of alanine aminotransferase(ALT), aspartate aminotransferase (AST), total bilirubin（TBIL） and TGFβ1 were significantly higher than those of the model group(P＜0.001). Masson trichrome staining showed that the intervention group had mild bridging fibrosis and less lymphocyte infiltration. No typical pseudolobule was found. Transmission electron microscopy demonstrated that hepatic cell injury in the intervention group was significantly less than that in the model group and slight collagen fibers were observed in the sinus hepaticus and Disse space. ConclusionsPFD has a significant antifibrosis effect in experimental rats, which was presumably caused by inhibiting the production of TGFβ1.

Key words: Pirfenidone; Fibrosis, liver; Wistar rats; transforming growth factor β1

中图分类号:

R575.2

杜磊，王昌源，张立华，谭炳芹. 吡非尼酮对实验性大鼠肝纤维化的作用[J]. 山东大学学报(医学版), 2009, 47(11): 50-54.

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