Division of Geriatrics Medicine and Gerontology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
J Invest Dermatol. 2018 Feb;138(2):434-443. doi: 10.1016/j.jid.2017.09.030. Epub 2017 Oct 24.
Chronic wounds are among the most devastating and difficult to treat consequences of diabetes. Dysregulation of the skin renin-angiotensin system is implicated in abnormal wound healing in diabetic and older adults. Given this, we sought to determine the effects of topical reformulations of the angiotensin type 1 receptor blockers losartan and valsartan and the angiotensin-converting enzyme inhibitor captopril on wound healing in diabetic and aged mice with further validation in older diabetic pigs. The application of 1% valsartan gel compared with other tested formulations and placebo facilitated and significantly accelerated closure time and increased tensile strength in mice, and was validated in the porcine model. One percent of valsartan gel-treated wounds also exhibited higher mitochondrial content, collagen deposition, phosphorylated mothers against decapentaplegic homologs 2 and 3 and common mothers against decapentaplegic homolog 4, alpha-smooth muscle actin, CD31, phospho-vascular endothelial growth factor receptor 2, and p42/44 mitogen-activated protein kinase. Knockout of the angiotensin subtype 2 receptors abolished the beneficial effects of angiotensin type 1 receptor blockers, suggesting a role for angiotensin subtype 2 receptors in chronic wound healing.
慢性伤口是糖尿病最具破坏性和最难治疗的后果之一。皮肤肾素-血管紧张素系统的失调与糖尿病和老年人的异常伤口愈合有关。有鉴于此，我们试图确定血管紧张素 1 型受体阻滞剂氯沙坦和缬沙坦以及血管紧张素转换酶抑制剂卡托普利的局部配方对糖尿病和老年小鼠伤口愈合的影响，并在老年糖尿病猪中进一步验证。与其他测试配方和安慰剂相比，1%缬沙坦凝胶的应用促进并显著加速了小鼠的闭合时间和拉伸强度，并且在猪模型中得到了验证。1%缬沙坦凝胶处理的伤口还表现出更高的线粒体含量、胶原蛋白沉积、磷酸化母亲抗 decapentaplegic 同源物 2 和 3 以及常见的母亲抗 decapentaplegic 同源物 4、α-平滑肌肌动蛋白、CD31、磷酸化血管内皮生长因子受体 2 和 p42/44 丝裂原激活蛋白激酶。血管紧张素亚型 2 受体的敲除消除了血管紧张素 1 型受体阻滞剂的有益作用，表明血管紧张素亚型 2 受体在慢性伤口愈合中起作用。
