Dual neovascular targets of vascular endothelial growth factor receptors and platelet-derived growth factor receptor ameliorate thioacetamide induced liver fibrosis in rats  

作　　者：Bin Xiong Yaowei Bai Jiacheng Liu Tongqiang Li Yingliang Wang Chen Zhou 

机构地区：[1]Department of Interventional Radiology,The First Affiliated Hospital of Guangzhou Medical University,Guangzhou,Guangdong,China [2]Department of Radiology,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,Hubei,China [3]Hubei Province Key Laboratory of Molecular Imaging,Wuhan,Hubei,China

出　　处：《Portal Hypertension & Cirrhosis》2024年第1期1-13,共13页门静脉高压与肝硬化（英文）

基　　金：National Natural Science Foundation of China,Grant/Award Number:81873917。

摘　　要：Aims:Neovascularization plays a crucial role in liver fibrosis(LF),and blocking vascular endothelial growth factor receptors(VEGFR)has been shown to improve fibrosis.The aim of our study was to investigate the role of dual neovascularization targets,VEGFR,and platelet-derived growth factor receptor(PDGFR),in ameliorating fibrosis.Methods:In vitro,we observed the effects of apatinib(APA)(a VEGFR inhibitor)and donafenib(DON)(a VEGFR and PDGFR inhibitor)on the activation,proliferation,and apoptosis of hepatic stellate cells(HSCs)from rats and humans.In vivo,we established a thioacetamide(TAA)-induced liver fibrosis rat model to explore the antifibrosis effect of APA and DON.We used the method of random table to randomly divide the rats into 4 groups.We detected the expression of angiogenesis-related proteins using Western blot and immunohistochemistry.Results:APA and DON inhibited the proliferation and activation of HSCs,promoted apoptosis of HSCs,and arrested the S phase of the cell cycle in vitro.We also found that DON had a stronger inhibitory effect on HSCs.In vivo,APA and DON ameliorated liver fibrosis,reduced collagen deposition andα-SMA expression in rats,and DON had a stronger improvement effect.APA and DON downregulated the expression of VEGFR2 while inhibiting the phosphorylation of Akt and ERK1/2.DON can act through both VEGF and PDGF pathways,whereas APA can only act through the VEGF pathway.Conclusion:Antiangiogenesis is a promising approach for the treatment of fibrosis.Compared with a single-target drug(APA),the dual-target drug(DON)can achieve better therapeutic effects.

关 键 词：ANTIANGIOGENESIS apatinib donafenib FIBROSIS 

分 类 号：R575.2[医药卫生—消化系统]