作　　者： (刘天凤）; (马丽）; (李艳婷）; (韩飞）; (宋爱华）; (尹然）;

机构地区： 沈阳药科大学药学院,辽宁沈阳110016

出　　处： 《沈阳药科大学学报》 2017年第8期644-653,共10页

摘　　要： 目的筛选栀子大黄汤(Zhi-Zi-Da-Huang decoction,ZZDHD)抗肝内胆汁淤积的有效部位,分析表征有效部位的化学成分。方法采用α-萘异硫氰酸酯(α-naphthylisothiocyanate,ANIT)制备大鼠急性肝内胆汁淤积模型,通过检测大鼠血清谷丙转氨酶(alanine aminotransferase,ALT)、碱性磷酸酶(alkaline phosphatase,ALP)、总胆汁酸(total bile acid,TBA)、总胆红素(total bilirubin,TBIL)、γ-谷氨酰转肽酶(γ-glutamyltranspeptidase,γ-GT)和肝组织丙二醛(malondialdehyde,MDA)、超氧化物歧化酶(superoxide dismutase,SOD)的水平,对栀子大黄汤的5个不同溶剂萃取部位进行药效学评价,筛选出栀子大黄汤抗肝内胆汁淤积有效部位;应用超高效液相色谱-傅立叶变换离子回旋共振质谱(UHPLC-FT-ICR MS)方法,对有效部位的化学成分进行快速定性分析。结果栀子大黄汤乙酸乙酯部位能非常显著改善模型大鼠血清ALT和TBIL水平(P<0.01),并显著改善血清ALP、TBA、γ-GT和肝组织MDA、SOD水平(P<0.05);栀子大黄汤正丁醇部位对模型大鼠血清和肝组织的各项检测指标水平均具有非常显著的改善作用(P<0.01);UHPLC-FT-ICR MS分析在乙酸乙酯部位定性表征了55个化学成分,在正丁醇部位定性表征了65个化学成分。结论通过药效学评价,筛选出乙酸乙酯部位和正丁醇部位为栀子大黄汤抗肝内胆汁淤积的有效部位;通过高分辨质谱鉴定,揭示了有效部位的化学成分;为栀子大黄汤抗肝内胆汁淤积药效物质的阐明和进一步研究开发奠定了基础。 Objective To screen the effective fractions of Zhi-Zi-Da-Huang decoction （ZZDHD）against intrahepatic cholestasis, and to analyze and characterize the chemical constituents in the effective fractions. Methods The model of intrahepatic cholestasis were produced with ot-naphthylisothiocyanate（ANIT） in rats. The effective fractions of ZZDHD against the intrahepatic cholestasis were screened out by detecting the levels of alanine aminotransferase （ ALT）, alkaline phosphatase （ ALP ）, total bile acid （ TBA）, total bilirubin （ TBIL）, y-glutamyltranspeptidase （ y-GT ） in serum, and the content of malondialdehyde （ MDA）, the activity of superoxide dismutase （SOD） in livers to evaluate the pharmacodynamic effects of five different extractive fractions of ZZHDD. The chemical constituents of the effective fractions were qualitative analyzed by ultra high performance liquid chromatography coupled to Fourier transform ion cyclotron resonance mass spectrometry （UHPLC-FT-ICR MS ）method. Results The ethyl acetate layer of ZZDHD can very significantly improved the serum ALT and TBIL levels （ P 〈 0.01 ）, and significantly improved the serum ALP, TBA, y-GT levels and hepatic MDA, SOD levels （ P 〈 0.05 ） of model rats. The n-butyl alcohol layer of ZZDI-ID exhibited extremely significant improve effect to all the serum and hepatic biochemical indexes of model rats（P 〈0.01 ）. Using UHPLC-bT-ICR MS method,55 compounds from the ethyl acetate layer and 65 compounds from the n-butyl alcohol layer of ZZDHD were identified. Conclusions The ethyl acetate layer and the n-butyl alcohol layer are deemed to the effective fractions of ZZDHD against the intrahepafic cholestasis according to the pharmacodynamic evaluation. The chemical constituents of effective fractions were revealed by high resolution mass spectrometry identification. This paper can provide a basis for the effective substances and further development studies of ZZDHD on anti-intrahepatic cholestasis.

关 键 词： 栀子大黄汤 肝内胆汁淤积 有效部位 萘异硫氰酸酯 超高效液相色谱 傅立叶变换离子回旋共振质谱 化学成分