沙棘经PXR/NF-κB通路减缓免疫性肝损伤小鼠肝脏CYP2C下调  

Sea-buckthorn slows down-regulation of CYP 2C in mice with liver injury by BCG-induced via PXR/NF-κB pathway

作　　者：郝佩佩 曹盈莹 邹慧琼 丁瑞峰[3] 白雪峰[4] 薛永志[1,2] HAO Pei-pei;CAO Ying-ying;ZOU Hui-qiong;DING Rui-feng;BAI Xue-feng;XUE Yong-zhi(Inner Mongolia University of Science and Technology Baotou Medical College,Baotou Inner Mongolia 014060,China;School of Basic Medicine and Forensic Medicine,Inner Mongolia University of Science and Technology Baotou Medical College,Baotou Inner Mongolia 014060,China;First Affiliated Hospital of Inner Mongolia University of Science and Technology Baotou Medical College,Baotou Inner Mongolia 014060,China;Baotou Cancer Hospital,Baotou Inner Mongolia 014060,China)

机构地区：[1]内蒙古科技大学包头医学院,内蒙古包头014060 [2]内蒙古科技大学包头医学院基础医学与法医学院,内蒙古包头014060 [3]内蒙古科技大学包头医学院第一附属医院,内蒙古包头014060 [4]包头市肿瘤医院,内蒙古包头014060

出　　处：《中国药理学通报》2023年第12期2320-2324,共5页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81460567,82160709);内蒙古自然科学基金资助项目(No 2009MS1104,2014MS0813,2019MS08198,2023MS08066)。

摘　　要：目的探讨沙棘(sea-buckthorn)是否通过PXR/NF-κB通路,减缓卡介苗(BCG)诱导的免疫性肝损伤小鼠肝脏细胞色素P4502C(CYP2C)下调。方法采用单次尾静脉注射BCG 125 mg·kg-1复制免疫性肝损伤小鼠模型用于乙型肝炎相关研究,将小鼠随机分为control组、BCG组、BCG+沙棘颗粒(sea-buckthorn granule,SG)(分别灌胃50、100、200 mg·kg-1,每日2次)组和BCG+PCN(腹腔注射100 mg·kg-1,每日1次)组。ELISA法检测血清转氨酶和肝组织中TNF-α、IL-1β的表达,Western blot检测肝脏NF-κB p65核蛋白和孕烷X受体(pregnane X receptor,PXR)、CYP2C总蛋白表达,HE染色观察小鼠肝脏的病理变化。结果沙棘抑制TNF-α、IL-1β、NF-κB p65的过表达,且缓解CYP2C、PXR蛋白表达下调,肝脏病理和血清转氨酶均有所改善,且呈剂量依赖性;用PXR的小鼠特异性激动剂PCN干预后与SG高剂量组相似。结论沙棘可以经PXR/NF-κB通路,减缓免疫性肝损伤小鼠CYP2C的下调。Aim To explore whether sea-buckthorn slows down-regulation of hepatic cytochrome P4502C(CYP 2C)in mice with liver injury by BCG vaccine(BCG)-induced via PXR/NF-κB pathway.Methods The mouse model of liver injury was induced by a single tail vein injection of BCG 125 mg·kg-1 for hepatitis B research,and the mice were randomly divided into control group,BCG group,BCG+sea-buckthorn granules(SG)group(gavage 50,100,200 mg·kg-1,twice a day),BCG+PCN group(intraperitoneal injection 100 mg·kg-1,once a day).The levels of serum transaminase and TNF-αand IL-1βin liver tissue were detected by ELISA.The nuclear protein expression NF-κB p65 and the total protein expression of pregnane X receptor(PXR),CYP2C in liver were detected by Western blot.Liver pathological changes were observed by HE staining.Results Sea-buckthorn inhibited overexpression of TNF-α,IL-1βand NF-κB p65,alleviated the down-regulation of CYP2C and PXR protein expression,and improved liver pathology and serum transaminase in a dose-dependent manner.After intervention with PCN,a mouse specific agonist of PXR,it was similar to the high dose group of SG.Conclusion Sea-buckthorn slows down-regulation of CYP2C in mice with liver injury by BCG-induced via PXR/NF-κB pathway.

关 键 词：卡介苗 沙棘 NF-ΚB PXR CYP2C 乙型肝炎 

分 类 号：R-332[医药卫生] R186.2R282.71R345.99R392.11R512.62