Granulocyte colony-stimulating factor reduces biliary fibrosis and ductular reaction in a mouse model of chronic cholestasis  

作　　者：Trinh Van Le Thanh Minh Dang Huy Quang Do Ai-Xuan Le Holterman Hong-Thuy Phan-Thi Thong Tan Tran Nhung Hai Truong 

机构地区：[1]Laboratory of Stem Cell Research and Application,University of Science-VNUHCM,Ho Chi Minh City,Vietnam [2]Vietnam National University,Ho Chi Minh City,Vietnam [3]Department of Pediatrics and Surgery,University of Illinois College of Medicine,Chicago,IL,USA [4]Faculty of Biology and Biotechnology,University of Science-VNUHCM,Ho Chi Minh City,Vietnam

出　　处：《Liver Research》2023年第1期90-98,共9页肝脏研究（英文）

基　　金：funded by the Prometheus USA(www.prometheususa.org)and Vietnam National Foundation for Science&Technology Development(NAFOSTED)under grant number 108.05e2017.30.

摘　　要：Background:Biliary atresia is a rare congenital bile duct disease that is the leading cause of liver fibrosis in neonates.Granulocyte colony-stimulating factor(GCSF)is a potential therapy for hepatocellular diseases,but data on GCSF for cholestatic conditions remain limited.Materials and methods:The current study examines the role of GCSF in improving bile duct obstruction in mice.Two doses were administered:10.0 mg/kg/day and 61.5 mg/kg/day,which is the animal equivalent dose of 5.0 mg/kg in humans.Seven days(D7)after bile duct ligation(BDL),Swiss mice were treated with phosphate buffered saline or GCSF for 5 days.The intrahepatic adaptive response of BDL mice was evaluated on postsurgical days D12,D19,and D26.Results:Treatment with 61.5 mg/kg of GCSF resulted in a significant increase in circulating leukocytes and neutrophils on D12.Amelioration of liver injury,as shown by reduced aspartate aminotransferase levels,increased albumin levels and survival rate,as well as reduced intrahepatic inflammation and hepatic myeloperoxidase expression,downregulated ductular proliferation,periportal fibroblast activation,and fibrosis,enhanced expressions of hepatocyte growth factor,peroxisome proliferator-activated receptoralpha,and ki67,and suppressed expression of cleaved caspase-3 protein,was noted after treatment with 61.5 mg/kg of GCSF.Additionally,GCSF treatment was associated with an increased number of intrahepatic cd3-Sca1tc-Kitt bone marrow cells.

关 键 词：Bile duct ligation(BDL) Biliary fibrosis Ductular reaction Granulocyte colony-stimulating factor(GCSF) Hepatic stellate cell(HSC) 

分 类 号：R575.7[医药卫生—消化系统]