Department of Special Treatment, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China ; Department of Hepatobiliary Surgery, Shuguang Hospital, Shanghai, China.
PLoS One. 2013 Aug 30;8(8):e73492. doi: 10.1371/journal.pone.0073492. eCollection 2013.
Angiogenesis is a fundamental part of the response to tissue injury, which is involved in the development of hepatic fibrosis. Vascular endothelial growth factor plays an important role in angiogenesis. The expression of VEGF is increased during hepatic fibrogenesis and correlates with the micro-vessel density. In this study, we investigated the effects of bevacizumab, an anti-angiogenetic drug, on the formation of hepatic fibrosis. We found that bevacizumab could attenuate the development of hepatic fibrosis and contribute to the protection of liver function. Bevacizumab was also found to downregulate the expression α-SMA and TGF-β1, which have been reported to be profibrogenic genes in vivo. We also observed that the expression of VEGF increased significantly during the development of hepatic fibrosis and CCl4 was found to induce hepatocytes to secrete VEGF, which led to the activation and proliferation of HSCs. Bevacizumab was also found to block the effects of the hepatocytes on the activation and proliferation of HSCs. Our results suggest that bevacizumab might alleviate liver fibrosis by blocking the effect of VEGF on HSCs. Bevacizumab might be suitable as a potential agent for hepatic fibrosis therapy.
血管生成是组织损伤反应的一个基本部分，它参与肝纤维化的发展。血管内皮生长因子在血管生成中起重要作用。VEGF 的表达在肝纤维化过程中增加，并与微血管密度相关。在这项研究中，我们研究了抗血管生成药物贝伐珠单抗对肝纤维化形成的影响。我们发现贝伐珠单抗可以减轻肝纤维化的发展，并有助于保护肝功能。贝伐珠单抗还被发现下调了 α-SMA 和 TGF-β1 的表达，这两种基因在体内被报道具有促纤维化作用。我们还观察到 VEGF 的表达在肝纤维化的发展过程中显著增加，CCl4 被发现诱导肝细胞分泌 VEGF，导致 HSCs 的激活和增殖。贝伐珠单抗还被发现阻断了肝细胞对 HSCs 的激活和增殖的影响。我们的结果表明，贝伐珠单抗可能通过阻断 VEGF 对 HSCs 的作用来缓解肝纤维化。贝伐珠单抗可能适合作为肝纤维化治疗的潜在药物。
