Abstract：
Liver 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.
摘要：
肝纤维化和肝硬化，是由慢性肝损伤引起的，代表了具有全球重要性的常见和棘手的临床挑战。然而,缺乏有效的治疗方法。因此,本研究探讨了多沙唑嗪对肝纤维化的影响.将四氯化碳(CCl4)注入小鼠体内,建立肝纤维化模型。每天通过管饲法施用多沙唑嗪(5和10mg/kg)。HE染色,Masson染色,天狼星红染色，扫描电子显微镜，西方印迹,实时PCR，和免疫荧光分析进行评估小鼠的肝纤维化和肝窦毛细血管化。细胞计数试剂盒-8测定，西方印迹,免疫荧光分析，管形成,并对人脐静脉内皮细胞（HUVEC）和人肝窦内皮细胞（HHSEC）进行了transwell迁移测定，以阐明多沙唑嗪的潜在机制。多沙唑嗪减轻CCl4诱导的小鼠肝纤维化和肝窦毛细血管化。在HUVEC和HHSEC中,血管生成被多沙唑嗪减弱。这项研究表明，多沙唑嗪通过减轻正弦毛细血管化和肝脏血管生成来减轻肝纤维化。
