Bingül İlknur, Başaran-Küçükgergin Canan, Aydın A Fatih, Çoban Jale, Doğan-Ekici Işın, Doğru-Abbasoğlu Semra, Uysal Müjdat
Department of Biochemistry, Istanbul Medical Faculty, Istanbul University, Çapa, Istanbul, Turkey.
Department of Biochemistry, Yeditepe University Medical Faculty, Kayışdağı, Istanbul, Turkey.
Environ Toxicol Pharmacol. 2016 Jul;45:170-8. doi: 10.1016/j.etap.2016.05.033. Epub 2016 Jun 1.
The aim of this study was to investigate the effect of betaine (BET) on alcoholic liver fibrosis in rats. Fibrosis was experimentally generated with ethanol plus carbon tetrachloride (ETH+CCl4) treatment. Rats were treated with ETH (5% v/v in drinking water) for 14 weeks. CCl4 was administered intraperitoneally (i.p.) 0.2mL/kg twice a week to rats in the last 6 weeks with/without commercial food containing BET (2% w/w). Serum hepatic damage markers, tumor necrosis factor-α, hepatic triglyceride (TG) and hydroxyproline (HYP) levels, and oxidative stress parameters were measured together with histopathologic observations. In addition, α-smooth muscle-actin (α-SMA), transforming growth factor-β1 (TGF-β1) and type I collagen (COL1A1) protein expressions were assayed immunohistochemically to evaluate stellate cell (HSC) activation. mRNA expressions of matrix metalloproteinase-2 (MMP-2) and its inhibitors (TIMP-1 and TIMP-2) were also determined. BET treatment diminished TG and HYP levels; prooxidant status and fibrotic changes; α-SMA, COL1A1 and TGF-β protein expressions; MMP-2, TIMP-1 and TIMP-2 mRNA expressions in the liver of fibrotic rats. In conclusion, these results indicate that the antifibrotic effect of BET may be related to its suppressive effects on oxidant and inflammatory processes together with HSC activation in alcoholic liver fibrosis.
本研究旨在探讨甜菜碱（BET）对大鼠酒精性肝纤维化的影响。通过乙醇加四氯化碳（ETH+CCl4）处理实验性诱导肝纤维化。大鼠用ETH（饮用水中5% v/v）处理14周。在最后6周，每周两次给大鼠腹腔注射（i.p.）0.2mL/kg CCl4，同时给予或不给予含BET（2% w/w）的市售食物。检测血清肝损伤标志物、肿瘤坏死因子-α、肝甘油三酯（TG）和羟脯氨酸（HYP）水平以及氧化应激参数，并进行组织病理学观察。此外，采用免疫组织化学方法检测α-平滑肌肌动蛋白（α-SMA）、转化生长因子-β1（TGF-β1）和I型胶原蛋白（COL1A1）蛋白表达，以评估星状细胞（HSC）激活情况。还测定了基质金属蛋白酶-2（MMP-2）及其抑制剂（TIMP-1和TIMP-2）的mRNA表达。BET处理降低了纤维化大鼠肝脏中的TG和HYP水平、促氧化状态和纤维化变化；α-SMA、COL1A1和TGF-β蛋白表达；MMP-2、TIMP-1和TIMP-2 mRNA表达。总之，这些结果表明，BET的抗纤维化作用可能与其对酒精性肝纤维化中氧化和炎症过程以及HSC激活的抑制作用有关。
