[干扰素-α对四氯化碳诱导的大鼠肝纤维化的治疗作用]

[Curative effect of interferon-alpha on rat liver fibrosis induced by CCl4].

作者信息

Yang Hui-xiang, Yi Yan-rong

机构信息

Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha 410008, China.

出版信息

Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2008 Oct;33(10):919-25.

PMID:19001734

Abstract

OBJECTIVE

To explore the curative effect and the mechanism of interferon-alpha (IFN-alpha) on rat liver fibrosis induced by CCl4.

METHODS

Thirty-nine male SD rats were randomly divided into 3 groups. The rats in the normal control group (n=10) received subcutaneous injection of peanut oil (0.003 mL/g body weight) for 10 weeks. Rat liver fibrosis was induced in 29 rats by 0.003 mL/g subcutaneous injection of 40% CCl4 (CCl4: peanut oil = 2:3), twice weekly for 10 weeks. In the 7th week, these 29 rats were randomly divided into a liver fibrosis group without treatment (n=15) and an IFN-alpha treatment group (n=14), which received subcutaneous injection of IFN-alpha-2b at 10(6) units per rat. The rats' liver tissue was collected and HE and Masson staining were performed to observe of pathological changes, stage of liver fibrosis,and semi-quantitative scoring. Immunohistochemistry was used to detect the expression of Collagen I, alpha-smooth muscle actin (alpha-SMA),and transforming growth factor-beta1 (TGF-beta1) in the rat liver.

RESULTS

The stage of liver fibrosis, semi-quantitative scoring of Masson staining, and immunohistochemical staining of Collagen I in the liver fibrosis group were significantly higher than those of the normal controls (All P<0.01), and those in the IFN-alpha treatment group were significantly lower than those of the liver fibrosis group(P<0.05). The semi-quantitative immunohistochemical scoring of alpha-SMA and TGF-beta1 in the liver fibrosis group was significantly higher than those of the normal control (All P<0.01), and that in the IFN-alpha treatment group was significantly lower than that of the liver fibrosis group (All P<0.05).

CONCLUSION

Treatment of IFN-alpha can decrease the liver fibrogenesis induced by CCl4 in rats. The anti-fibrosis effect of IFN-alpha may be attributed to the inhibition of the hepatic stellate cells' activation to decrease TGF-beta1 expression.

摘要

目的

探讨α-干扰素（IFN-α）对四氯化碳诱导的大鼠肝纤维化的治疗效果及作用机制。

方法

将39只雄性SD大鼠随机分为3组。正常对照组（n = 10）大鼠皮下注射花生油（0.003 mL/g体重），共10周。29只大鼠皮下注射0.003 mL/g 40%四氯化碳（四氯化碳：花生油 = 2:3）诱导肝纤维化，每周2次，共10周。在第7周时，将这29只大鼠随机分为未治疗的肝纤维化组（n = 15）和IFN-α治疗组（n = 14），治疗组大鼠皮下注射10(6)单位的IFN-α-2b。收集大鼠肝脏组织，进行HE和Masson染色，观察病理变化、肝纤维化程度及半定量评分。采用免疫组化法检测大鼠肝脏中I型胶原、α-平滑肌肌动蛋白（α-SMA）和转化生长因子-β1（TGF-β1）的表达。

结果

肝纤维化组的肝纤维化程度、Masson染色半定量评分及肝脏I型胶原免疫组化染色均显著高于正常对照组（均P<0.01），而IFN-α治疗组的上述指标均显著低于肝纤维化组（P<0.05）。肝纤维化组α-SMA和TGF-β1免疫组化半定量评分均显著高于正常对照组（均P<0.01），IFN-α治疗组的上述指标显著低于肝纤维化组（均P<0.05）。