Department of Bioartificial Organs, Institute for Frontier Medical Sciences, Kyoto University, 53 Kawahara Cho, Sakyo-ku, Kyoto 606-8507, Japan.
Surg Today. 2013 Jun;43(6):661-9. doi: 10.1007/s00595-012-0379-2. Epub 2012 Oct 17.
We describe a new rat model of biliary atresia, induced by biliary ablation with pure ethanol.
A catheter was inserted and fixed in the common bile duct of male rats. Saline or pure ethanol was injected through the catheter and the animals were monitored for 8 weeks thereafter. We measured total bilirubin (T-Bil), aspartate aminotransferase (AST), alanine transaminase (ALT), and hyaluronic acid (HA) and examined liver biopsy specimens immunohistochemically for α-smooth muscle actin staining (α-SMA) and transforming growth factor-β1 (TGF-β1).
The ethanol injection group animals were further divided into a temporary and a persistent liver dysfunction group. In the persistent group, T-Bil, AST, ALT and HA levels were significantly higher after 8 weeks in the persistent group than in the control group and the temporary group. In the ethanol injection group, α-SMA expression was prominent in the surrounding proliferative bile ducts and portal areas. The distribution of TGF-β1 was found prominently in hepatocytes in the center of nodules and in ductular epithelial cells.
This study characterizes the effects of ethanol-induced bile duct injury in rats, resulting in sclerosing cholangitis and its secondary effects. We believe that this experimental model will prove useful in the study of biliary atresia.
我们描述了一种新的胆管闭锁大鼠模型,通过纯乙醇胆管消融诱导。
将导管插入并固定在雄性大鼠的胆总管中。通过导管注入生理盐水或纯乙醇,然后对动物进行 8 周的监测。我们测量总胆红素(T-Bil)、天门冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)和透明质酸(HA),并对肝活检标本进行α-平滑肌肌动蛋白染色(α-SMA)和转化生长因子-β1(TGF-β1)免疫组化检查。
乙醇注射组动物进一步分为暂时性和持续性肝功能障碍组。在持续性组中,8 周后持续性组的 T-Bil、AST、ALT 和 HA 水平明显高于对照组和暂时性组。在乙醇注射组中,周围增生胆管和门脉区α-SMA 表达明显。TGF-β1 的分布在结节中心的肝细胞和胆管上皮细胞中明显发现。
本研究描述了乙醇诱导的胆管损伤在大鼠中的作用,导致硬化性胆管炎及其继发效应。我们相信,这种实验模型将有助于研究胆道闭锁。