法尼醇X受体在急性淤胆型肝炎大鼠模型中的表达及大黄素的干预作用

Effect of emodin on expression of farnesoid X receptor in rats with acute cholestatic hepatitis

摘要:

目的 研究核受体法尼醇X受体（FXR）在急性淤胆型肝炎大鼠模型中的表达及大黄素的干预作用。方法 将90只Sprague-Dawley成年大鼠随机分为正常对照组、模型组和大黄素干预组，每组30只。模型组和大黄素干预组给予α-异硫氰酸萘酯（ANIT）50 mg/kg一次灌胃，建立大鼠淤胆型肝炎动物模型，正常对照组给予等体积麻油进行替代；大黄素干预组分别于造模前连续4 d及造模后每日给予20 mg/kg大黄素灌胃，直至各组大鼠分别于造模后24、48、72 h处死，模型组和正常对照组给予等体积羧甲基纤维素钠溶液进行替代。实时荧光定量PCR法检测肝组织中FXR mRNA表达的变化；全自动生化分析仪检测血清总胆红素（TB）、直接胆红素（DB）、丙氨酸氨基转移酶（ALT）及胆汁酸（TBA）的水平。结果 造模后各时间点，模型组肝组织中FXR mRNA表达水平均低于正常对照组（均P<0.05），大黄素干预组肝组织中FXR mRNA表达水平均高于模型组（均P<0.05）；模型组大鼠血清ALT、TB、DB、TBA水平在造模后各时间点较对照组均显著增高（均P<0.05），而大黄素干预组大鼠血清ALT、TB、DB、TBA水平较模型组均显著降低（均P<0.05）。结论 大黄素可显著降低ANIT诱导的淤胆型肝炎大鼠血清中TB、DB、ALT、TBA水平，其作用机制可能与促进FXR表达有关。

Abstract:

Objective To investigate the expression of farnesoid X receptor (FXR) and the effect of emodin on FXR expression in a rat model of acute cholestatic hepatitis. Methods Ninety adult Sprague-Dawley rats were randomly divided into normal control, model, and emodin groups (n=30 each). The model and emodin groups were given alpha-naphthylisothiocyanate (ANIT) 50 mg/kg by gavage to establish an animal model of cholestatic hepatitis, while the normal control group was given an equal volume of sesame oil. The emodin group was given emodin by gavage every day from 4 days before the model was prepared until the time of sacrifice, while the model and normal control groups were given an equal volume of sodium carboxymethyl cellulose solution. At 24, 48 and 72 hours after the model was prepared, serum level of total bilirubin (TB), direct bilirubin (DB), alanine aminotransferase (ALT), and total bile acids (TBA) were measured by Aeroset automatic biochemical analyzer, and the mRNA expression of FXR in the liver tissue was measured by real-time PCR. Results At all time points FXR mRNA expression in the model group decreased, but serum levels of TB, DB, ALT and TBA increased significantly compared with the normal control group (P<0.05). The emodin group had significantly higher mRNA expression of FXR and significantly lower serum levels of TB, DB, ALT, and TBA compared with the model group (P<0.05). Conclusions Emodin can significantly reduce serum levels of TB, DB, ALT, and TBA in rats with ANIT-induced cholestatic hepatitis, probably by promoting FXR expression.