Co-administration of ursodeoxycholic acid with rosuvastatin/ezetimibe in a non-alcoholic fatty liver disease model  

作　　者：Sang Hyun Seo Da Hyun Lee Yu Seol Lee Kyung Joo Cho Hye Jung Park Hye Won Lee Beom Kyung Kim Jun Yong Park Do Young Kim Sang Hoon Ahn Soo Han Bae Seung Up Kim 

机构地区：[1]Department of Internal Medicine,Graduate School of Medicine Science,Brain Korea 21 Project,Yonsei University College of Medicine,Seoul,Republic of Korea [2]Yonsei Liver Center,Severance Hospital,Seoul,Republic of Korea [3]Severance Biomedical Science Institute,Graduate School of Medical Science,Brain Korea 21 Project,Yonsei University College of Medicine,Seoul,Republic of Korea [4]Severance Biomedical Science Institute,Yonsei Biomedical Research Institute,Yonsei University College of Medicine,Seoul,Republic of Korea [5]Department of Internal Medicine,Institute of Gastroenterology,Yonsei University College of Medicine,Seoul,Republic of Korea

出　　处：《Gastroenterology Report》2022年第1期440-450,共11页胃肠病学报道（英文）

基　　金：supported by Daewoong Pharmaceutical company,and was supported by a Faculty Research Grant from the Yonsei University College of Medicine(6-2019-0068 to S.H.Bae);by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute(KHIDI);funded by the Ministry of Health&Welfare,Republic of Korea(HI17C0913 and HI16C0257 to S.H.Bae);supported by the National Research Foundation of Korea(NRF)grant funded by the Korea government(MSIT)(NRF-2022R1A2C2003438 to S.H.Bae,NRF-2021R1C1C2095694 to D.H.Lee);by Basic Science Research Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Science,ICT&Future Planning(2019R1A2C4070136 to S.U.Kim).

摘　　要：Background Ursodeoxycholic acid(UDCA),statins,and ezetimibe(EZE)have demonstrated beneficial effects against nonalcoholic fatty liver disease(NAFLD).We investigated the efficacy of the combination of UDCA and the mix of rosuvastatin(RSV)/EZE in the treatment of NAFLD.Methods NAFLD mouse models were developed by injecting thioacetamide,fasting,and high-carbohydrate refeeding,highfat diet,and choline-deficient L-amino acid-defined high-fat diet(CDAHFD).Low-dose UDCA(L-UDCA;15 mg/kg)or highdose UDCA(H-UDCA;30 mg/kg)was administered with RSV/EZE.We also employed an in vitro model of NAFLD developed using palmitic acid-treated Hepa1c1c7 cells.Results Co-administration of RSV/EZE with UDCA significantly decreased the collagen accumulation,serum alanine aminotransferase(ALT)levels,and mRNA levels of fibrosis-related markers than those observed in the vehicle group in thioacetamide-treated mice(all P<0.01).In addition,in the group fasted and refed with a high-carbohydrate diet,UDCA/RSV/EZE treatment decreased the number of apoptotic cells and serum ALT levels compared with those observed in the vehicle group(all P<0.05).Subsequently,H-UDCA/RSV/EZE treatment decreased the number of ballooned hepatocytes and stearoyl-CoA desaturase 1(SCD-1)mRNA levels(P=0.027)in the liver of high-fat diet-fed mice compared with those observed in the vehicle group.In the CDAHFD-fed mouse model,UDCA/RSV/EZE significantly attenuated collagen accumulation and fibrosis-related markers compared to those observed in the vehicle group(all P<0.05).In addition,UDCA/RSV/EZE treatment significantly restored cell survival and decreased the protein levels of apoptosis-related markers compared to RSV/EZE treatment in palmitic acid-treated Hepa1c1c7 cells(all P<0.05).Conclusion Combination therapy involving UDCA and RSV/EZE may be a novel strategy for potent inhibition of NAFLD progression.

关 键 词：non-alcoholic fatty liver disease non-alcoholic steatohepatitis ursodeoxycholic acid ROSUVASTATIN EZETIMIBE 

分 类 号：R575.5[医药卫生—消化系统]