Soylu Ali-Riza, Aydogdu Nurettin, Basaran Umit-Nusret, Altaner Semsi, Tarcin Orhan, Gedik Nursal, Umit Hasan, Tezel Ahmet, Dokmeci Gulbin, Baloglu Huseyin, Ture Mevlut, Kutlu Kemal, Kaymak Kadir
Division of Gatroenterology, Trakya University, Turkey.
World J Gastroenterol. 2006 Nov 14;12(42):6835-41. doi: 10.3748/wjg.v12.i42.6835.
To investigate whether antioxidants vitamin E and C can retard development of hepatic fibrosis in the biliary-obstructed rats.
Fifty Wistar albino rats were randomly assigned to 5 groups (10 rats in each). Bile duct was ligated in 40 rats and they were treated as follows: group vitC, vitamin C 10 mg/kg sc daily; group vitE, vitamin E 15 mg/kg sc daily; group vitEC, both of the vitamins; bile duct-ligated (BDL, control) group, physiological saline sc. The fifth group was assigned to sham operation. At the end of fourth week, the rats were decapitated, and hepatic tissue biochemical collagen content and collagen surface area were measured. Hepatic tissue specimens were histopathologically evaluated according to Scheuer system. Serum hyaluronate levels were measured by ELISA method.
Despite being higher than sham group, hepatic collagen level was significantly decreased in each of the vitC, vitE and vitEC groups (32.7 +/- 1.2, 33.8 +/- 2.9, 36.7 +/- 0.5 mug collagen/mg protein, respectively) compared to BDL (48.3 +/- 0.6 mg collagen/g protein) (P < 0.001 for each vitamin group). Each isolated vitamin C, isolated vitamin E and combined vitamin E/C supplementation prevented the increase in hepatic collagen surface density (7.0% +/- 1.1%, 6.2% +/- 1.7%, 12.3% +/- 2.0%, respectively) compared to BDL (17.4% +/- 5.6%) (P < 0.05 for each). The same beneficial effect of vitamin C, vitamin E and combined vitamin E/C treatment was also observed on the decrease of serum hyaluronate levels compared to BDL group (P < 0.001). The relative liver and spleen weights, serum transaminases, cholestatic enzymes, bilirubins and histopathological inflammation scores were not different between the antioxidant treatment groups and the control. However, fibrosis staging scores were obviously reduced only in the vitamin E/C combination group (vit EC: 2.4 +/- 0.8 vs BDL: 3.1 +/- 0.7; P < 0.05).
Each antioxidant vitamin E, vitamin C and their combination retard hepatic fibrosis in biliary-obstructed rats. Oxidative stress may play a role in the pathogenesis of hepatic fibrosis in secondary biliary cirrhosis.
研究抗氧化剂维生素E和维生素C是否能延缓胆管梗阻大鼠肝纤维化的发展。
50只Wistar白化大鼠随机分为5组(每组10只)。40只大鼠行胆管结扎术,并按以下方式处理:维生素C组,每日皮下注射维生素C 10 mg/kg;维生素E组,每日皮下注射维生素E 15 mg/kg;维生素E/C组,两种维生素均用;胆管结扎(BDL,对照)组,皮下注射生理盐水。第五组行假手术。在第四周结束时,将大鼠断头,测量肝组织生化胶原含量和胶原表面积。肝组织标本根据Scheuer系统进行组织病理学评估。采用ELISA法测定血清透明质酸水平。
尽管维生素C组、维生素E组和维生素E/C组的肝胶原水平均高于假手术组,但与BDL组(48.3±0.6 mg胶原/g蛋白)相比,各治疗组的肝胶原水平均显著降低(分别为32.7±1.2、33.8±2.9、36.7±0.5 μg胶原/mg蛋白)(各维生素组P<0.001)。与BDL组(17.4%±5.6%)相比,单独补充维生素C、单独补充维生素E以及联合补充维生素E/C均可防止肝胶原表面密度增加(分别为7.0%±1.1%、6.2%±1.7%、12.3%±2.0%)(各P<0.05)。与BDL组相比,维生素C、维生素E以及联合应用维生素E/C治疗在降低血清透明质酸水平方面也有相同的有益作用(P<0.001)。抗氧化剂治疗组与对照组之间的相对肝脾重量、血清转氨酶、胆汁淤积酶、胆红素及组织病理学炎症评分无差异。然而,仅维生素E/C联合治疗组的纤维化分期评分明显降低(维生素E/C组:2.4±0.8 vs BDL组:3.1±0.7;P<0.05)。
抗氧化剂维生素E、维生素C及其联合应用可延缓胆管梗阻大鼠的肝纤维化。氧化应激可能在继发性胆汁性肝硬化肝纤维化的发病机制中起作用。