目的 探究清热卡森颗粒对α-萘异硫氰酸酯（ANIT）诱导的肝内胆汁淤积性肝损伤模型大鼠的保护作用及机制。方法 将SPF级雄性SD大鼠36只随机分为正常对照组，模型对照组，清热卡森颗粒低、中、高剂量组（1 g·kg^-1，2 g·kg^-1，和4g·kg^-1）以及阳性对照组（熊去氧胆酸，UDCA，60 mg·kg^-1），每组6只。清热卡森颗粒各治疗组和阳性对照组分别预防性灌胃给药，连续5天，实验第3天采用ANIT（60 mg·kg^-1）灌胃构建急性肝内胆汁淤积模型，正常对照组给予等量橄榄油。实验第6天，大鼠腹主动脉取血，检测血浆中天门冬氨酸氨基转移酶（AST）、丙氨酸氨基转移酶（ALT）、碱性磷酸酶（ALP）、胆汁酸（TBA）、还原型谷胱甘肽（GSH）、丙二醛（MDA）、超氧化物歧化酶（SOD）；收集胆汁，计算胆汁流量；取肝脏，称肝重，计算肝重比；观察肝脏组织病理学变化；Western blot法检测肝脏核受体法尼醇X受体（FXR）和胆汁酸合成酶、转运体以及氧化应激通路核因子E2相关因子2（Nrf2）及下游调控蛋白表达的变化。结果 清热卡森颗粒能改善胆汁淤积大鼠的肝重比、胆汁流量水平和病理损伤情况，恢复血浆中AST，ALT，ALP，TBA，MDA的含量水平（P<0.05）；上调FXR，BSEP，MRP2，NRF2，GCLM，HO-1蛋白表达（P<0.05），下调NTCP，CYP7A1，CYP8B1蛋白表达（P<0.05）。结论 清热卡森颗粒可以缓解ANIT诱导的肝内胆汁淤积性肝损伤，其作用机制可能与调控FXR信号通路介导的胆汁酸平衡以及NRF2信号通路介导的抗氧化应激作用有关。

Objective: The aim of this paper was to explore the protective effect and mechanism of Qingrekasen granules on α-naphthalene isothiocyanate (ANIT)-induced intrahepatic cholestasis liver injury in rats. Methods: Thirty-six male SPF SD rats were randomly divided into normal control group, model control group, low, medium and high dose groups of Qingrekasen granules (1 g·kg-1, 2 g·kg-1 and 4 g·kg-1) and positive control group (ursodeoxycholic acid, UDCA, 60 mg·kg-1). The Qingrekasen granules and UDCA group were given preventive intragastric administration for 5 consecutive days. On the third day, the acute intrahepatic cholestasis model was builded with ANIT. The normal control group was given equivalent volume of olive oil. Blood was taken from the abdominal aorta of the rats on the sixth day, then separated plasma and detected aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), bile acid (TBA)，Glutathione (GSH), malondialdehyde (MDA), superoxide dismutase (SOD). Next, collecting bile and liver were to calculate bile flow and liver weight ratio. Besides observing liver histopathological changes. Finally, Western blot was used to detect changes in the expression of liver nuclear receptor FXR, bile acid synthetase, transporters, and oxidative stress genes Nrf2. Results: The research results showed Qingrekasen granules can improve liver weight ratio, bile flow level and pathological injury in cholestasis rats, also recover the serum levels of ALT, AST, ALP, TBA and MDA ( P < 0.05). What’s more, it can up-regulate the protein expression of FXR, BSEP, MRP2, NRF2, GCLM, and HO-1 ( P <0.05), and down-regulate the protein expression of NTCP, CYP7A1, and CYP8B1 ( P < 0.05). Conclusion: The finding suggested that Qingrekasen granules can alleviate the intrahepatic cholestasis liver injury induced by ANIT. Its mechanism may be related to the regulation of bile acid balance mediated by FXR signaling pathway and the anti-oxidative stress mediated by NRF2 signaling pathway.

R285.5

武汉市科学技术局知识专项课题（2022020801010441）：基于miRNA的毛菊苣治疗妊娠期胆汁淤积的作用机制研究，负责人：刘东。