摘要
[目的]探讨胆淤方对胆汁淤积模型小鼠胆管周围炎及法尼醇X受体1(FXR1)表达的影响。[方法]72只雄性C57BL/6小鼠随机分为正常组(N)8只、模型组(M)12只、奥贝胆酸组(OCA)16只、胆淤方低剂量组(DJ)18只和胆淤方高剂量组(GJ)18只。N组小鼠饲料不含DDC,M、OCA、DJ和GJ组采用0.07%DDC饲料连续喂养8周。从第3周开始,OCA组予OCA溶液0.03 g/(kg·d)^-1灌胃,DJ组予胆淤方11 g/(kg·d)^-1灌胃,GJ组予胆淤方33 g/(kg·d)^-1灌胃,对照组给予相同体积的双蒸水灌胃处理。干预6周后收集各组小鼠血清及肝组织,试剂盒检测生化指标,苏木精-伊红染色观察肝内胆管周围炎,免疫组化观察细胆管反应和FXR1蛋白表达,WB检测FXR1蛋白表达量。[结果](1)M组ALT、AST、ALP和TBA水平较N组显著升高(P<0.05);干预后,OCA、DJ和GJ组ALT、AST、ALP、TBA水平均较M组显著下降(P<0.05);与OCA组比较,GJ组的ALT、AST水平下降更加显著(P<0.05)。(2)苏木精-伊红染色示M组胆管周围大量炎性细胞浸润,OCA、DJ和GJ组胆管周围炎症较M组减轻。(3)CK19染色示M组汇管区大量细小胆管增生,OCA、DJ和GJ组胆管增生较M组减少。(4)FXR1染色和WB结果示OCA、DJ、GJ组FXR1表达量均较M组增多,以GJ组增加更显著。[结论]胆淤方具有减轻胆汁淤积模型小鼠胆管周围炎和激活FXR1表达的作用,这为研究胆淤方的药效机制提供依据。
[Objective]To investigate the effect of Danyu decoction on peribiliary inflammation and FXR1 expression in cholestasis model mice.[Methods]Seventy-two male C57 BL/6 mice were randomly divided into normal group(N,8 mice),model group(M,12 mice),obeticholic acid group(OCA,16 mice), low-dose group(DJ,18 mice)and high-dose group(GJ,18 mice)of Danyu decoction.Diet given to the N group did not contain DDC,while M,OCA,DJ and GJ groups were fed with 0.07% DDC for 8 weeks.From the third week,the OCA group was orally administered with OCA 0.03 g/(kg·d)-1,the DJ group was orally administered with Danyu decoction 11 g/(kg·d)-1,the GJ group was administered orally with Danyu decoction 33 g/(kg·d)-1,and the control groups were administered with the same volume of water.After 6 weeks of intervention,the serum and liver tissues of each group of mice were collected,the biochemical indicators were detected by the kit,the inflammatory response in the intrahepatic manifold area was observed by HE staining,the intrahepatic bile duct response was observed by immunohistochemistry,and the FXR1 protein expression was detected by immunohistochemistry and Western Bolt.[Results](1)The levels of ALT,AST,ALP,and TBA in group M were significantly higher than those in group N(P<0.05).After intervention,the levels of ALT,AST,ALP,and TBA in the OCA,DJ,and GJ groups were significantly lower than those in the M group.(P<0.05);Compared with the OCA group,the levels of ALT and AST in the GJ group decreased more significantly(P<0.05).(2)HE staining showed that a large number of inflammatory cells infiltrated around the bile duct in the M group,and the biliary duct inflammation in the OCA,DJ,and GJ groups was reduced compared with the M group.(3)CK19 staining showed a large number of small bile duct hyperplasia in the manifold area of group M, which was reduced in the OCA,DJ,and GJ groups compared to group M.(4)FXR1 staining and WB results showed that the expression of FXR1 in the OCA,DJ,and GJ groups was significantly higher than that in the M group,and the expression in the GJ group was more significant.[Conclusion]Danyu decoction can reduce the biliary tract inflammation and activate the expression of FXR1 in cholestasis model mice,which provides a basis for studying the pharmacodynamic mechanism of Danyu decoction.
作者
郝娟
黄恺
陶艳艳
刘成海
HAO Juan;HUANG Kai;TAO Yan-yan;LIU Cheng-hai(Institute of Liver Diseases,Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China;Department of Endocrinology,Shanghai Traditional Chinese Medicine-Integrated Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai 200082,China;Shanghai Key Laboratory of Clinical Chinese Medicine,Shanghai 201203,China;Key Laboratory of Liver and Kidney Diseases,Shanghai University of Traditional Chinese Medicine,Ministry of Education,Shanghai 201203,China)
出处
《中国中西医结合消化杂志》
CAS
2020年第10期776-781,共6页
Chinese Journal of Integrated Traditional and Western Medicine on Digestion
基金
国家自然科学基金青年基金项目(No:81803874)。
关键词
胆汁淤积
碱性磷酸酶
法尼醇X受体
胆淤方
健脾补肾
cholestasis
alkaline phosphatase
farnesoid X receptor
Danyu decoction
spleen and kidney
