Accurate Assessment and Tracking the Process of Liver-Specific Injury by the Residual Tissue Activity of Carboxylesterase 1 and Dipeptidyl Peptidase 4  

作　　者：Qiusha Pan Peifang Song Zhenhua Ni Xingkai Qian Anqi Wang Liwei Zou Yong Liu Ping Wang Weidong Zhang Hong Ma Ling Yang 

机构地区：[1]Center for Systems Pharmacokinetics,Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China [2]Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education,Zunyi Medical University,Zunyi 563000,China [3]Putuo Hospital,Shanghai University of Traditional Chinese Medicine,Shanghai 200062,China [4]Shanghai Institute of Acupuncture and Meridian,Shanghai 200030,China [5]School of Life and Pharmaceutical Sciences,Dalian University of Technology,Dalian 116024,China

出　　处：《Engineering》2022年第12期153-165,共13页工程（英文）

基　　金：This article is supported by the National Key Research and Development Program of China(2017YFC1702000,2020YFC0845400,and 2021YFE0200900);National Natural Science Foundation of China(81773810,81922070,and 81973393).The authors would like to thank Peter for his help in publishing the article,and the support provided by Zhaoyan(Suzhou)New Drug Research Center Co,.Ltd.

摘　　要：Accurately assessing and tracking the progression of liver-specific injury remains a major challenge in the field of biomarker research.Here,we took a retrospective validation approach built on the mutuality between serum and tissue biomarkers to characterize the liver-specific damage of bile duct cells caused by a-naphthyl isothiocyanate(ANIT).We found that carboxylesterase 1(CES1),as an intrahepatic marker,and dipeptidyl peptidase 4(DPP-IV),as an extrahepatic marker,can reflect the different pathophysiologies of liver injury.Levels of CES1 and DPP-IV can be used to identify liver damage itself and the inflammatory state,respectively.While the levels of the conventional serological biomarkers alkaline phosphatase(ALP),alanine aminotransferase(ALT),and aspartate aminotransferase(AST)were all concomitantly elevated in serum and tissues after ANIT-induced injury,the levels of bile acids decreased in bile,increased in serum,and ascended in intrahepatic tissue.Although the level of γ-glutamyl transpeptidase(γ-GT)changed in an opposite direction,the duration was much shorter than that of CES1 and was quickly restored to normal levels.Therefore,among the abovementioned biomarkers,only CES1 made it possible to specifically determine whether the liver cells were destroyed or damaged without interference from inflammation.CES1 also enabled accurate assessment of the anti-cholestasis effects of ursodeoxycholic acid(UDCA;single component)and Qing Fei Pai Du Decoction(QFPDD;multicomponent).We found that both QFPDD and UDCA attenuated ANIT-induced liver damage.UDCA was more potent in promoting bile excretion but showed relatively weaker anti-injury and antiinflammatory effects than QFPDD,whereas QFPDD was more effective in blocking liver inflammation and repairing liver damage.Our data highlights the potential of the combined use of CES1(as an intrahepatic marker of liver damage)and DPP-IV(as an extrahepatic marker of inflammation)for the accurate evaluation and tracking of liver-specific injury—an application that allows

关 键 词：Carboxylesterase 1 Dipeptidyl peptidase 4 Liver injury Validation tracking 

分 类 号：R575[医药卫生—消化系统]