Li Yanyan, Yang Huixiang
Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha 410008, China.
Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2011 Mar;36(3):243-8. doi: 10.3969/j.issn.1672-7347.2011.03.009.
To explore the curative effect and the underlying mechanism of interferon-α (IFN-α) on rat liver fibrosis induced by CCl(4).
Forty-five Wistar male rats were randomly divided into 3 groups: a normal control group (n=15), a liver fibrosis group (n=15) and a IFN-α treatment group (n=15). The rats of the control group and the liver fibrosis group received peanut oil (0.2 mL/100 g body weight), twice a week for 8 weeks. The rats of the liver fibrosis group and the IFN-α treatment group were received intraperitoneal injection of 50% CCl(4) (CCl(4):peanut oil=1:1, 0.2 mL/100 g body weight, ip) or IFN-α (CCl(4):peanut oil=1:1, 0.2 mL/100 g body weight, ip), twice a week for 8 weeks. In the 9th week, the rats of IFN-α treatment group were switch to receive IFN-α at 100 000 units (s.c.) per day for 3 weeks. The rats were all sacrificed in the 11th week. Pathological changes of liver, semi-quantitative scoring of rat liver was observed. Tissue hydroxyproline, the mRNA expression of Collagen I, Collagen III, transforming growth factor-beta 1 (TGF-β1), connective tissue growth factor (CTGF), a-smooth muscle actin (α-SMA), matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) of rat liver was detected. The protein expression of MMP-9 and TIMP-1 also was detected.
Semi-quantitative scoring of inflammation,semi-quantitative scoring of liver fibrosis, hydroxyproline and collagen in the IFN-α treatment group were significantly lower than those in the liver fibrosis group (all P<0.05). The mRNA expression of TGF-β1, CTGF, α-SMA and TIMP-1, and the protein expression of TIMP-1 in the IFN-α treatment group were significantly lower than those in the liver fibrosis group (all P<0.05). But there was no significant difference in MMP-9 between the IFN-α treatment group and the liver fibrosis group.
IFN-α can decrease the liver fibrogenesis induced by CCl(4) in rats and reduce liver inflammation response. The anti-fibrosis effect of IFN-α may be related to decrease in TGF-β1, CTGF and TIMP-1 expression and to inhibiting of the hepatic satellite cells' activation and extracellular matrix synthesis.
探讨干扰素-α（IFN-α）对四氯化碳（CCl₄）诱导的大鼠肝纤维化的治疗效果及潜在机制。
45只雄性Wistar大鼠随机分为3组：正常对照组（n = 15）、肝纤维化组（n = 15）和IFN-α治疗组（n = 15）。对照组和肝纤维化组大鼠每周两次给予花生油（0.2 mL/100 g体重），共8周。肝纤维化组和IFN-α治疗组大鼠每周两次腹腔注射50% CCl₄（CCl₄∶花生油 = 1∶1，0.2 mL/100 g体重，腹腔注射）或IFN-α（CCl₄∶花生油 = 1∶1，0.2 mL/100 g体重，腹腔注射），共8周。在第9周，IFN-α治疗组大鼠改为每天皮下注射100 000单位IFN-α，共3周。所有大鼠在第11周处死。观察肝脏病理变化，对大鼠肝脏进行半定量评分。检测大鼠肝脏组织羟脯氨酸、Ⅰ型胶原、Ⅲ型胶原、转化生长因子-β1（TGF-β1）、结缔组织生长因子（CTGF）、α-平滑肌肌动蛋白（α-SMA）、基质金属蛋白酶-⑨（MMP-9）和金属蛋白酶组织抑制剂-1（TIMP-1）的mRNA表达。同时检测MMP-9和TIMP-1的蛋白表达。
IFN-α治疗组的炎症半定量评分、肝纤维化半定量评分、羟脯氨酸和胶原含量均显著低于肝纤维化组（均P < 0.05）。IFN-α治疗组TGF-β1、CTGF、α-SMA和TIMP-1的mRNA表达以及TIMP-1的蛋白表达均显著低于肝纤维化组（均P < 0.05）。但IFN-α治疗组与肝纤维化组MMP-9无显著差异。
IFN-α可减轻CCl₄诱导的大鼠肝纤维化，降低肝脏炎症反应。IFN-α的抗纤维化作用可能与降低TGF-β1、CTGF和TIMP-1表达，抑制肝星状细胞活化及细胞外基质合成有关。
