来氟米特对四氯化碳诱导的大鼠肝纤维化的抑制作用。

Inhibitory effect of leflunomide on hepatic fibrosis induced by CCl4 in rats.

作者信息

Yao Hong-wei, Li Jun, Chen Ji-qiang, Xu Shu-yun

机构信息

Zhejiang Respiratory Drugs Research Laboratory of State Drugs Administration of China, School of Medicine, Zhejiang University, Hangzhou 310031, China.

出版信息

Acta Pharmacol Sin. 2004 Jul;25(7):915-20.

PMID:15210065

Abstract

AIM

To study the effect of leflunomide on CCl4-induced hepatic fibrosis in rats.

METHODS

Hepatic fibrosis was induced by subcutaneous injection with 50% CCl4 in Sprague-Dawley rats. The amount of CCl4 administered was 1 mg/kg. The alanine aminotransferase (ALT), aspartate aminotransferase (AST), nitric oxide (NO) levels in plasma and hydroxyproline (Hyp) contents in liver tissue were assayed by spectrophotometry. The hyaluronic acid (HA) and procollagen III (PC III) were assessed by radioimmunoassay. The transforming growth factor-beta1 (TGF-beta1) in serum was determined by ELISA. The nuclear factor-kappa B (NF-kappaB) in liver tissue was examined by immunohistochemistry. Liver samples collected after 12 weeks of CCl4 treatment were stained with hematoxylin and eosin.

RESULTS

Leflunomide (1, 3, and 9 mg/kg) significantly decreased indices of liver and spleen, the serum transaminase (AST, ALT) activities, HA and PC III levels, and Hyp contents in liver tissue in rats of hepatic fibrosis. Histopathological examination showed leflunomide had inhibitory effect on fibrogenesis and formation of pseudolobulus. Furthermore, leflunomide significantly inhibited NF-kappaB expression in liver tissue, and reduced elevated serum TGF-kappa1 and NO levels in rats of hepatic fibrosis.

CONCLUSION

Leflunomide showed inhibitory action on hepatic fibrosis induced by CCl4 in rats.

摘要

目的

研究来氟米特对四氯化碳诱导的大鼠肝纤维化的影响。

方法

采用皮下注射50%四氯化碳的方法诱导Sprague-Dawley大鼠肝纤维化。四氯化碳的给药量为1mg/kg。采用分光光度法检测血浆中丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）、一氧化氮（NO）水平以及肝组织中羟脯氨酸（Hyp）含量。采用放射免疫分析法检测透明质酸（HA）和Ⅲ型前胶原（PCⅢ）。采用酶联免疫吸附测定法测定血清中转化生长因子-β1（TGF-β1）。采用免疫组织化学法检测肝组织中核因子-κB（NF-κB）。对四氯化碳处理12周后采集的肝脏样本进行苏木精-伊红染色。

结果

来氟米特（1、3和9mg/kg）显著降低了肝纤维化大鼠的肝脏和脾脏指数、血清转氨酶（AST、ALT）活性、HA和PCⅢ水平以及肝组织中Hyp含量。组织病理学检查显示来氟米特对纤维生成和假小叶形成具有抑制作用。此外，来氟米特显著抑制肝组织中NF-κB表达，并降低肝纤维化大鼠血清中升高的TGF-κ1和NO水平。