Singh Anoop K, Sharma Anuj, Warren James, Madhavan Subhashree, Steele Keith, RajeshKumar N V, Thangapazham Rajesh L, Sharma Shekhar C, Kulshreshtha Dinesh K, Gaddipati Jaya, Maheshwari Radha K
Center for Combat Casualty and Life Sustainment Research, Department of Pathology, Uniformed Services University of the Life Sciences, Bethesda, Maryland 20814, USA.
Planta Med. 2007 Mar;73(3):251-6. doi: 10.1055/s-2007-967119. Epub 2007 Feb 22.
Tissue repair and wound healing are complex processes that involve inflammation, granulation and tissue remodeling. Angiogenesis plays a central role in wound healing. Earlier, we have shown that picroliv, a natural product obtained from the roots of Picrorhiza kurrooa, up-regulates the expression of vascular endothelial growth factor in human umbilical vein endothelial cells and of insulin-like growth factor in rats during hypoxia. In the present study, we have investigated the effect of picroliv in an ex vivo rat aorta ring model of angiogenesis. Picroliv enhanced the sprouting and migration of endothelial cells. We also investigated punch wound healing on days 4 and 7 after wounding by histology, morphometry and collagenization. The data showed improved re-epithelialization, neovascularization and migration of various cells such as endothelial, dermal myofibroblasts and fibroblasts into the wound bed after picroliv treatment. Immunohistochemical localization showed increased VEGF and alpha smooth muscle actin staining consistent with an increased number of microvessels in granulation tissue. These findings suggest that picroliv could be developed as a therapeutic angiogenic agent for the restoration of the blood supply in diseases involving inadequate blood supply such as limb ischemia, ischemic myocardium and wound healing.
组织修复和伤口愈合是复杂的过程,涉及炎症、肉芽形成和组织重塑。血管生成在伤口愈合中起核心作用。此前,我们已经表明,胡黄连苷(一种从胡黄连根中获得的天然产物)在缺氧条件下可上调人脐静脉内皮细胞中血管内皮生长因子的表达以及大鼠体内胰岛素样生长因子的表达。在本研究中,我们研究了胡黄连苷在体外大鼠主动脉环血管生成模型中的作用。胡黄连苷增强了内皮细胞 的芽生和迁移。我们还通过组织学、形态测量学和胶原化研究了创伤后第4天和第7天的打孔伤口愈合情况。数据显示,胡黄连苷治疗后,伤口床的再上皮化、新血管形成以及内皮细胞、真皮肌成纤维细胞和成纤维细胞等各种细胞的迁移均得到改善。免疫组织化学定位显示,与肉芽组织中微血管数量增加一致,血管内皮生长因子(VEGF)和α平滑肌肌动蛋白染色增加。这些发现表明,胡黄连苷可开发成为一种治疗性血管生成剂,用于恢复诸如肢体缺血、缺血性心肌和伤口愈合等血液供应不足疾病中的血液供应。