活血清解灵对胆汁淤积肝病大鼠胆汁酸代谢的影响  

Effect of Huoxue Qingjie Ling on bile acid metabolism of cholestatic liver disease rats

作　　者：李婉华 李锡晶[2] 张婷[2] 沈洪昇 张桂贤[2] 刘洪斌[2] LI Wanhua;LI Xijing;ZHANG Ting;SHEN Hongsheng;ZHANG Guixian;LIU Hongbin(Tianjin Medical University,Tianjin 300070,China;不详)

机构地区：[1]天津医科大学,天津300070 [2]天津市医药科学研究所

出　　处：《山东医药》2020年第19期21-24,共4页Shandong Medical Journal

基　　金：天津医科大学十三五综投学科建设项目中西医结合(11601502-XK0135);天津市卫生健康委、天津市中医药管理局中医、中西医结合科研课题(2019106)。

摘　　要：目的探讨活血清解灵对胆汁淤积性肝病大鼠胆汁酸代谢的影响。方法将48只大鼠随机分为6组,分别为空白组、模型组、复方甘草酸苷胶囊组、活血清解灵低、中、高剂量组。除空白组外,其余组以α-异硫氰酸萘酯(ANIT,100 mg/kg)灌胃1次,制备胆汁淤积性肝病模型。复方甘草酸苷胶囊组予0.023 g/kg复方甘草酸苷胶囊,活血清解灵低、中、高剂量组分别给予4.1、8.1、16.2 g/kg活血清解灵连续灌胃给药4 d。第5天进行胆管插管手术留取胆汁,通过LC-MS/MS测定各组大鼠胆汁中18种胆汁酸的含量,腹主动脉取血检测各组血清总胆红素和总胆汁酸含量,Western blotting法检测肝组织中牛磺胆酸钠转运蛋白(NTCP)含量。结果与空白组比,模型组胆汁中各胆汁酸成分浓度均下降(P均<0.05),仅牛磺鹅去氧胆酸(TCDCA)浓度增高(P<0.05),血清中总胆红素和总胆汁酸含量增高(P均<0.05),肝组织中NTCP含量降低(P<0.01);与模型组相比,活血清解灵高剂量组胆汁中去氧胆酸(DCA)、牛磺熊去氧胆酸(TUDCA)、牛磺猪去氧胆酸(THDCA)、甘氨胆酸(GCA)、甘氨熊去氧胆酸(GUDCA)浓度升高(P均<0.05),TCDCA浓度降低(P<0.05)。血清中总胆红素和总胆汁酸含量降低(P均<0.05),肝组织中NTCP含量增高(P<0.05)。结论活血清解灵可通过调节胆汁酸代谢有效治疗大鼠胆汁淤积性肝病。Objective To investigate the effect of Huoxue Qingjie Ling(herbs of activating the blood,clearing away heat,and releasing toxin)on bile acid metabolism in rats with cholestatic liver disease.Methods Wistar rats are randomly divided into 6 groups:blank group,model group,compound glycyrrhizin capsules group(0.023 g/kg),low-dose,medium-dose,and high-dose Huoxue Qingjie Ling groups(4.1,8.1,and 16.2 g/kg).Except for the blank control group,the rats in the other groups were given ANIT(100 mg/kg)by gavage to establish the cholestatic liver disease models;rats in the compound glycyrrhizin capsules group were intragastrically administered compound glycyrrhizin capsules for 4 d;and rats in the low-dose,medium-dose,and high-dose Huoxue Qingjie Ling groups were given 4.1,8.1,and 16.2 g/kg Huoxue Qingjie Ling for 4 d.The bile duct intubation was performed to retain bile on the fifth day,and serum was taken to test the IBI and TBA of each group.Eighteen bile acids in bile were detected by LC-MS/MS.The expression levels of NTCP proteins in the liver tissues were detected by Western blotting.Results Compared with the blank control group,the bile acids levels decreased in the model group(all P<0.05),but the concentration of TCDCA increased significantly(P<0.05),IBI and TBA in serum increased(both P<0.05),and the expression level of NTCP in the liver tissues decreased(P<0.01).Compare with the model group,the DCA,TUDCA,THDCA,GCA and GUDCA concentrations increased significantly(all P<0.05),TCDCA decreased significantly(P<0.05),IBI and TBA in serum decreased(both P<0.05),and the expression level of NTCP in the liver tissues increased in the high-dose Huoxue Qingjie Ling group(P<0.05).Conclusion Huoxue Qingjie Ling can effectively treat cholestatic liver disease in rats by regulating bile acid metabolism.

关 键 词：胆汁淤积性肝病 高效液相色谱-质谱联用法 胆汁 胆汁酸代谢 大鼠 

分 类 号：R575[医药卫生—消化系统]