大黄免煎颗粒对α-萘异硫氰酸酯诱导的肝内胆汁淤积大鼠氧化应激损伤的修复及核因子κB通路的调节作用研究  

Repair of Oxidative Stress Injury and Regulation of Nuclear FactorκB Pathway in Rats withα-Naphthalene Isothiocyanate-Induced Intrahepatic Cholestasis by Dahuang Granule Prescription

作　　者：张英[1] 侯伟娜 孙琦[1] 张莹[1] 李晓景 任晓华[1] 谢克让 安翠平[2] ZHANG Ying;HOU Weina;SUN Qi;ZHANG Ying;LI Xiaojing;REN Xiaohua;XIE Kerang;AN Cuiping(Dept.of Pharmacy,Shijiazhuang First Hospital,Shijiazhuang 050011,China;Dept.of Blood Transfusion,Shijiazhuang First Hospital,Shijiazhuang 050011,China)

机构地区：[1]石家庄市第一医院药剂科,石家庄050011 [2]石家庄市第一医院输血科,石家庄050011

出　　处：《中国医院用药评价与分析》2022年第6期680-683,共4页Evaluation and Analysis of Drug-use in Hospitals of China

基　　金：河北省中医药管理局科研计划项目(No.2018248)。

摘　　要：目的:研究大黄免煎颗粒对α-萘异硫氰酸酯(ANIT)诱导的肝内胆汁淤积大鼠氧化应激损伤的修复及核因子κB(NF-κB)通路的调节作用。方法:将60只大鼠随机分为对照组、模型组、大黄免煎颗粒组及阳性对照组,采用灌胃给予ANIT法建立肝内胆汁淤积大鼠模型;大黄免煎颗粒组大鼠灌胃给予大黄免煎颗粒4 g/kg,阳性对照组大鼠灌胃给予大熊去氧胆酸100 mg/kg,对照组及模型组大鼠灌胃给予等量0.9%氯化钠溶液,均为1日1次,连续给药14 d。测定大鼠血清丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、碱性磷酸酶(ALP)、谷氨酰转肽酶(GGT)、总胆红素(TBIL)和直接胆红素(DBIL)水平,肝组织超氧化物歧化酶(SOD)活性及丙二醛(MDA)、谷胱甘肽(GSH)水平,采用苏木精-伊红染色法进行肝组织病理学检查,采用蛋白质印迹法检测大鼠肝组织NF-κB p65及p-NF-κB p65蛋白水平。结果:与模型组比较,大黄免煎颗粒组大鼠血清ALT、AST、ALP、GGT、TBIL和DBIL水平,肝组织MDA、GSH水平,肝组织NF-κB p65及p-NF-κB p65水平显著降低,SOD水平显著升高,差异均有统计学意义(P<0.05);肝组织病理学改变显著改善。结论:大黄免煎颗粒能够明显修复大鼠肝功能及肝组织氧化应激损伤,改善胆汁代谢水平,其机制可能与调节NF-κB通路有关。OBJECTIVE:To study the repair of oxidative stress injury and regulation of nuclear factorκB(NF-κB)pathway in rats withα-naphthalene isothiocyanate(ANIT)-induced intrahepatic cholestasis by Dahuang granule prescription.METHODS:A total of 60 rats were randomly divided into the control group,model group,Dahuang granule prescription group and positive control group.The rat model of intrahepatic cholestasis was established by intragastric administration of ANIT.Rats in the Dahuang granule prescription group were intragastrically administered with Dahuang granule prescription 4 g/kg,rats in the positive control group were intragastrically administered with ursodeoxycholic acid 100 mg/kg,and rats in the control group and model group received the same amount of 0.9%sodium chloride solution by gavage,qd,for 14 d.The levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),alkaline phosphatase(ALP),glutyltransferase(GGT),total bilirubin(TBIL)and direct bilirubin(DBIL)in serum,the levels of superoxide dismutase(SOD),malondialdehyde(MDA)and glutathione(GSH)in liver tissue were determined.Liver histopathology was performed by Hematoxylin-Eosin staining,and protein levels of NF-κB p65 and p-NF-κB p65 were detected by western blotting.RESULTS:Compared with the model group,the levels of ALT,AST,ALP,GGT,TBIL and DBIL in serum,the levels of MDA and GSH,NF-κB p65 and p-NF-κB p65 in the liver tissue of the Dahuang granule prescription group decreased significantly,the SOD level increased significantly,the differences were statistically significant(P<0.05).The liver histopathology of rats was significantly improved.CONCLUSIONS:Dahuang granule prescription can significantly repair the liver function and oxidative stress injury of liver tissue,and improve the bile metabolism level,which may be related to the regulation of NF-κB pathway.

关 键 词：大黄免煎颗粒 肝内胆汁淤积 核因子κB通路 

分 类 号：R932[医药卫生—生药学] R96[医药卫生—药学]