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目的:通过建立梗阻性黄疸动物模型,观察胆固醇7α-羟化酶(cholesterol 7alpha-hydroxylase,CYP7A1)、类法尼醇X受体(farnesoid Xreceptor,FXR)及小异源二聚体伴侣受体(small heterodi mer partner,SHP)的表达变化,并分析CYP7A1和FXR、SHP之间的关系。方法:采用胆总管结扎术制备大鼠梗阻性黄疸模型,分别于术后1、3、14 d麻醉后放血处死。取大鼠肝脏,抽提总RNA,采用实时定量RT-PCR检测CYP7A1 mRNA表达;提取肝细胞核蛋白,采用蛋白质印迹技术检测FXR和SHP蛋白表达。结果:与假手术对照组相比,梗阻性黄疸组大鼠肝细胞CYP7A1 mRNA表达明显增强,FXR和SHP蛋白表达同步降低,差异均有统计学意义(P<0.001,P<0.05)。结论:CYP7A1表达增强可能与FXR、SHP表达减弱有关。
OBJECTIVE: To establish an animal model of obstructive jaundice to observe the effects of cholesterol 7alpha-hydroxylase (CYP7A1), farnesoid Xreceptor (FXR) and small heterodimeric chaperone receptor small heterodi mer partner (SHP), and to analyze the relationship between CYP7A1, FXR and SHP. Methods: The model of obstructive jaundice was established by bile duct ligation in rats. The model was anesthetized and then sacrificed on the 1st, 3rd, 14th day after operation. Total RNA was extracted from the liver of rats, and the expression of CYP7A1 mRNA was detected by real-time quantitative RT-PCR. The nuclear protein of hepatocytes was extracted and the protein expression of FXR and SHP was detected by Western blotting. Results: The expression of CYP7A1 mRNA in liver cells of obstructive jaundice group was significantly increased, while the expression of FXR and SHP protein decreased compared with that in sham operation group. The difference was statistically significant (P <0.001, P <0.05). Conclusion: The increased expression of CYP7A1 may be related to the weakened expression of FXR and SHP.