Abstract
in English, Chinese Objective: To investigate the role of farnesoid X receptor (FXR) and its downstream molecules small heterodimer partner (SHP), UDP-glucuronosyltransferase 2B4 (UGT2B4), and bile salt export pump (BSEP) in rats with acute cholestatic hepatitis. Methods: A total of 20 Sprague-Dawley rats were randomly divided into normal control group and model group, with 10 rats in each group. The rats in the model group were given a single dose (50 mg/kg) ofα-naphthyl isothiocyanate by gavage to establish the animal model of acute cholestatic hepatitis. Quantitative real-time PCR was used to measure the mRNA expression of FXR, UGT2B4, and BSEP in liver tissue at 48 hours after gavage. An automatic biochemical analyzer was used to measure the serum levels of total bilirubin, direct bilirubin, alanine aminotransferase, total bile acid, aspartate aminotransferase, alkaline phosphatase, andγ-glutamyl transferase. The independent samples t-test was used for comparison of means between groups. Results: The model group had significantly lower mRNA expression of FXR, SHP, UGT2B4, and BSEP in liver tissue than the normal control group (0.152±0.088/0.559±0.194/0.177±0.039/0.561±0.123 vs 1.137±0.215/1.512±0.309/2.394±0.462/1.631±0.376, t = 13.408, 8.260, 15.121, and 8.553, all P < 0.05). The model group had significantly higher liver function parameters than the normal control group (all P < 0.01). Conclusion: FXR, SHP, UGT2B4, and BSEP are involved in the development of acute cholestatic hepatitis. Reduced expression of FXR may cause reduced expression of downstream SHP, UGT2B4, and BSEP, increase the synthesis of bile acid, weaken detoxicating and transporting functions, and thus mediate the development of cholestatic hepatitis. 目的: 探讨核受体法尼醇X受体（FXR）及其相关下游分子小异源二聚体伴侣受体（SHP）、尿苷二磷酸葡萄糖苷酸转移酶2B4（UGT2B4）、胆盐输出泵（BSEP）在大鼠急性淤胆型肝炎中的作用。 方法: 将20只Sprague-Dawley（SD）大鼠随机分为正常对照组和模型组，每组10只。模型组给予α-异硫氰酸萘酯50 mg/kg一次灌胃建立急性淤胆型肝炎的动物模型，实时荧光定量PCR检测灌胃后48 h肝组织中FXR、SHP、UGT2B4、BSEP mRNA表达量。全自动生物化学分析仪检测血清总胆红素、直接胆红素、丙氨酸氨基转移酶、总胆汁酸、天冬氨酸氨基转移酶、碱性磷酸酶、γ-谷氨酰转移酶的水平。组间均数差异性比较采用两个独立样本的t检验。 结果: 模型组肝组织FXR、SHP、UGT2B4、BSEP mRNA的相对表达量分别为0.152±0.088、0.559±0.194、0.177±0.039、0.561±0.123，均低于正常对照组（分别为1.137±0.215、1.512±0.309、2.394±0.462、1.631±0.376，t值分别为13.408，8.260，15.121，8.553，P值均<0.05）；而肝功能各指标水平明显高于正常对照组（P值均<0.01）。 结论: FXR和SHP、UGT2B4、BSEP参与了急性淤胆型肝炎的发生，其中FXR的表达降低可能在急性淤胆型肝炎中作为始动环节引起其下游的SHP、UGT2B4、BSEP表达降低，导致胆汁酸合成增加，解毒及转运功能减弱，从而介导了胆汁淤积性肝炎的发生。