茵苓汤对α-萘异硫氰酸酯致肝内胆汁淤积大鼠肝损伤的保护作用和机制  

Protective effects of Yin-ling soup on liver injury of ANIT-induced intrahepatic cholestatic rats and its mechanism

作　　者：刘晓敏[1] 刘广洲[1] 姚欣欣[1] 王维纲[1] 兰汝春[1] 张春华[1] LIU Xiaomin;LIU Guangzhou;YAO Xinxin;WANG Weigang;LAN Ruchun;ZHANG Chunhua(Affiliated Hospital to Jilin Medical College,Jilin 132013,China)

机构地区：[1]吉林医药学院附属医院,吉林吉林132013

出　　处：《沈阳药科大学学报》2019年第12期1113-1118,共6页Journal of Shenyang Pharmaceutical University

基　　金：吉林省中医药管理局项目(2017248).

摘　　要：目的研究茵苓汤对α-萘异硫氰酸酯(α-naphthalene isothiocyanate,ANIT)致肝内胆汁淤积大鼠肝损伤的保护作用,并初步探讨其作用机制。方法60只SD大鼠随机分为正常组、模型组、阳性对照组(熊去氧胆酸,45 mg·kg^-1)和茵苓汤高、中、低剂量组(生药77.1、38.5、19.3 g·kg^-1),每组10只。以质量浓度20 g·L-1α-萘基异硫氰酸酯(ANIT)色拉油溶液5 mL·kg^-1一次性灌胃制备大鼠肝内胆汁淤积模型,造模48 h后,给药组按公斤体重灌胃给药,一日一次,连续7 d。测定大鼠血清中总胆红素(total bilirubin,TBIL)、直接胆红素(direct bilirubin,DBIL)、谷丙转氨酶(alanine transaminase,ALT)、谷草转氨酶(aspartate aminotransferase,AST)、碱性磷酸酶(alkaline phosphatase,ALP)、总胆汁酸(total bile acid,TBA)水平,2 h胆汁流量,光镜下进行肝脏病理组织形态学观察,测定肝脏组织超氧化物歧化酶(superoxide dismutase,SOD)、丙二醛(malonic dialdehyde,MDA)、谷胱甘肽过氧化物酶(glutathione peroxidase,GSH-Px)、过氧化氢酶(catalase from micrococcus lysodeikticus,CAT)活性,实时荧光定量PCR检测大鼠肝脏组织钠离子-牛磺胆酸协同转运蛋白(sodium taurocholate cotransporting polypeptide,NTCP)、胆盐输出泵(bile salt export pump,BSEP)和多药耐药相关蛋白2(multidrug resistance protein 2,MRP2)mRNA的表达量。结果茵苓汤能降低TBIL、DBIL、ALT、AST、ALP、TBA水平,提高胆汁流量,改善肝脏形态,降低肝组织MDA活性,提高SOD、GSH-Px、CAT活性,上调肝组织NTCP、BSEP和MRP2 mRNA表达量。结论茵苓汤对ANIT致肝内胆汁淤积大鼠具有保护作用,其作用机制可能与抗氧化应激和影响胆汁酸转运体有关。Objective To study the protective effect of Yin-ling soup on liver injury of ANIT-induced intrahepatic cholestatic rats and and to explore its mechanism.Methods 60 rats were randomly divided into blank group,model group,positive control group(UDCA,45 mg·kg^-1),Yin-ling soup high,medium and low dose groups(77.1,38.5,19.3 g·kg^-1),10 rats in each group.The intrahepatic cholestatic rats model was made with 100 mg·kg^-1 ANIT only one time.After 48 h,each group was administered once a day for 7 days.The detected index include the levels of total bilirubin(TBIL),direct bilirubin(DBIL),alanine transaminase(ALT),aspartate aminotransferase(AST),alkaline phosphatase(ALP)and total bile acid(TBA)in plasma,2 h bile flow,the contents of superoxide in liver homogenate.The pathological changes of the liver tissues were observed by hematoxylin and eosin(HE)staining and the expression levels of NTCP,BSEP and MRP2 mRNA in liver tissues.Results Yin-ling soup significantly decreased the levels of TBIL,DBIL,ALT,AST,ALP,TBA,2 h bile flow and the activity of MDA in liver homogenate,improved the activity of SOD,GSH-Px and CAT in liver homogenate,ameliorate liver morphology,raised relative expression level of NTCP,BSEP and MRP mRNA in liver tissue.Conclusion Yin-ling soup has protective effects on liver injury induced by ANIT in rat.The underling mechanism is possibly related to anti-oxidative stress and affecting bile acid transporter.

关 键 词：茵苓汤 Α-萘异硫氰酸酯 肝内胆汁淤积 肝损伤 

分 类 号：R285.5[医药卫生—中药学]