Objective To evaluate the effect of chenodeoxycholic acid (CDCA) in the treatment of hepatobil-iary disease, and to prove a new targets of FXR as treatment drug for obstructive jaundice. Methods Seventy-two 4-weeks-old male Sprague-Dawley (SD) rats were enrolled in this study. Forty-eight of the rats had the common bile duct ligated above the duodenum, and then cut and sutured to establish the rat model of bile duct obstruction (the study group). The other 24 rats had the common bile duct separated and then sutured (the control group). The morphological changes of liver tissue 1 d, 3 d, 7 d, and 14 d after bile duct obstruction were observed. The alanine aminotrans-ferase (ALT), total bilirubin (TB) and total bile acid (TBA) in serum were detected. The expression of FXR in different stage of bile duct obstruction was observed by immunohistochemistry. At the same time, the role of CDCA played in the process of rat bile duct obstruction was investigated. Results After bile duct obstruction, the rats suffered intra-hepatic cholangiectasis, fibroustissue hyperplasia, which relieved 14 d later. The levels of ALT, TB and TBA in serum were significantly increased as the increase of time after obstruction, reaching the peak on the 7th day after obstruction (P<0.05). The levels were decreased significantly on the 14th day after obstruction. CDCA could reduce the level of ALT, TB and TBA in serum to varying degrees. In addition, with the extension of time after obstruction, the expression of FXR was up-regulated reached the peak on the 7th day, which indicates that CDCA could inhibit the expression of FXR obviously. Conclusion Bile duct obstruction can lead to liver injury and fibroustissue hyperplasia, the degree of which is positively correlated between the level of ALT in serum. Bile duct obstruction leads to the increase of bile acid concentration, which stimulates the expression of FXR. FXR agonist (CDCA) can relieve the liver damage after biliary obstruction.%目的 探讨应用鹅脱氧胆酸(CDCA)治疗胆汁淤积性疾病的可行性.方法 取4周龄健康雄性SD大鼠72只,随机将其中48只大鼠的胆总管在十二指肠上方双重结扎后剪断然后缝合关腹,建立胆道阻塞大鼠动物模型.另外24只大鼠仅游离胆总管但并不结扎,然后缝合关腹作为对照组.观察大鼠胆管阻塞1d、3d、7d和14 d四个时段的肝脏组织形态学改变,并检测这四个不同时段的大鼠血清丙氨酸氨基转移酶(ALT)、总胆红素(TB)和总胆汁酸(TBA)等血液生化指标；通过免疫组化方法观察大鼠胆管阻塞不同时段的法尼酯衍生物X受体(FXR)表达变化,同时利用上述方法研究CDCA在大鼠胆管阻塞进程中的作用.结果 大鼠胆管阻塞后,肝内胆管扩张,纤维组织增生,但14d后症状有所缓解；随大鼠胆管阻塞时间延长,血清中ALT、TB和TBA明显升高.第7天达到峰值,与对照组比较差异有统计学意义(P＜0.05),第14天时均明显下降；CDCA可不同程度的降低大鼠血清中ALT、TB和TBA的水平.另外,随大鼠胆管阻塞时间的延长,FXR表达上调,第7天最为明显.CDCA治疗可明显减轻大鼠胆管阻塞后所致的肝脏损伤,CDCA可抑制FXR的表达上调.结论 胆管阻塞可导致肝损伤和肝纤维化,其程度和血清中的ALT水平呈密切相关.胆道阻塞时,胆汁酸浓度的上升刺激FXR表达上调,并随阻塞时间延长,FXR蛋白表达增高相对缓慢.FXR的激动剂——CDCA可减轻胆道阻塞后大鼠肝脏损害.
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