齐墩果酸对大鼠急性胆汁淤积肝损伤的保护作用

The Protective effect of oleanolic acid on acute cholestatic liver injury in rats

目的构建胆道结扎的胆汁淤积大鼠模型，研究齐墩果酸对急性胆汁淤积时胆酸排泌泵和核受体的影响。方法30只大鼠利用随机数字表法分为3组（每组10只）：假手术组（sham组）、胆道结扎组（BDL组，bile duct ligated组）和胆道结扎并灌胃齐墩果酸组（BDL＋OA组，bile duct ligated＋oleanolic acid组），连续处理7d后，处死大鼠，取其肝脏组织，提取RNA和总蛋白，分别在mRNA水平和蛋白水平对胆酸排泌泵和核受体进行研究。结果通过在mRNA水平的研究发现：胆道结扎后，大鼠肝脏胆酸排泌泵Mrp4和Oatp1表达均增高，与sham组相比，Mrp4在BDL组表达增高1．8倍，在BDL＋OA组表达增高2．3倍，差异有统计学意义；AhR在BDL组表达增高1．7倍，在BDL＋OA组表达增高2．8倍，差异具有统计学意义；Nrf2在BDL组表达增高1．5倍，在BDL＋OA组表达增高2．1倍，差异有统计学意义；而Oatp1在BDL组表达增高1．1倍，在BDL＋OA组表达增高1．3倍，差异不具有统计学意义。蛋白水平的研究结果显示：BDL组，Mrp4表达增高1．3倍，Oatp1表达增高1．5倍，AhR表达增高1．3倍，Nrf2表达增高1．4倍；BDL＋OA组，Mrp4表达增高1．8倍，AhR表达增高1．9倍，Nrf2表达增高1．8倍，各组差异有统计学意义，Oatp1表达增高1．4倍，与BDL组相比较差异无统计学意义。结论齐墩果酸能够促进急性阻塞性胆汁淤积大鼠肝脏胆酸排泌泵Mrp4、核受体AhR、Nrf2的表达上调。

Objective The protective effect of oleanolic acid on acute cholestatic liver injury in rats. Methods Thirty male SD rats were randomly divided into 3 groups （ n= 10 per group）： sham group, bile duct ligated （BDL） group, and bile duct ligated with oleanolic acid （BDL＋OA） group. After 7 days, liver samples in all rats were collected. Expressions of bile acids pump and nuclear receptors at mRNA and protein levels were detected by RT- qPCR and Western blotting. Results At mRNA level, the expression of Mrp4 and Oatpl expression in the BDL and BDL＋OA groups were increased as compared with that in the sham group. The expression of Mrp4 increased 1.8 times in the BDL group and increased 2.3 times in the BDL＋OA group （P〈0.05）, but the expression of Oatpl was not statistically significant; AhR was increased 1.7-fold in the BDL group and 2.8 times in the BDL＋OA group, Nrf2 was increased 1.5-fold in the BDL group and 2.1 times in the BDL＋OA group with statistically significant difference. At the protein level, in the BDL group, Mrp4 expression increased 1.3 times, Oatpl expression increased 1.5 times, AhR expression increased 1.3 times, Nrf2 expression increased 1.4 fold; in the BDL^OA group, Mrp4 expression increased 1.8 fold, AhR expression increased 1.9 fold, with statistical significance between the two groups. Oatpl expression increased 1.4-fold in the BDL＋OA group as compared with the BDL group showing no statistical significance. Conclusions Oleanolic acid stimulates the hepatic expression of bile acids pump Mrp4 associated with the activation of nuclear receptors AhR and Nrf2 in acute bile ductligated rats.