Affiliation:
1. Department of Gastroenterology Shandong Provincial Hospital Cheeloo College of Medicine Shandong University Jinan Shandong 250021 China
2. Department of Gastroenterology Shandong Provincial Hospital Affiliated to Shandong First Medical University Jinan Shandong 250021 China
3. Department of Gastroenterology Changzheng Hospital Naval Medical University Shanghai 200003 China
Abstract
AbstractLiver fibrosis and cirrhosis, which are caused by chronic liver injury, represent common and intractable clinical challenges of global importance. However, effective therapeutics are lacking. Therefore, the study examines the effect of doxazosin on liver fibrosis. Carbon tetrachloride (CCl4) is injected into mice to establish a liver fibrosis model. Doxazosin (5 and 10 mg/kg) is administered daily by gavage. HE staining, Masson staining, Sirius Red staining, scanning electron microscopy, western blotting, real‐time PCR, and immunofluorescence analysis are performed to estimate liver fibrosis and sinusoidal capillarization in mice. Cell Counting Kit‐8 assays, western blotting, immunofluorescence analysis, tube formation, and transwell migration assays are performed on human umbilical vein endothelial cells (HUVECs) and human hepatic sinusoidal endothelial cells (HHSECs) to elucidate the potential mechanism of doxazosin. Doxazosin alleviates liver fibrosis and sinusoidal capillarization in CCl4‐induced mice. Angiogenesis is attenuated by doxazosin in HUVECs and HHSECs. This study demonstrates that doxazosin attenuated liver fibrosis by alleviating sinusoidal capillarization and liver angiogenesis.