Topical Reformulation of Valsartan for Treatment of Chronic Diabetic Wounds
Topical Reformulation of Valsartan for Treatment of Chronic Diabetic Wounds
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DOI：
10.1016/j.jid.2017.09.030
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发表时间：
2018-02-01
影响因子：
6.5
通讯作者：
Walston, Jeremy
中科院分区：
文献类型：
--
作者：
Abadir, Peter;Hosseini, Sayed;Walston, Jeremy
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患者和老年人伤口愈合异常有关。鉴于此，我们试图确定局部重新配制的血管紧张素1型受体阻滞剂氯沙坦和缬沙坦和血管紧张素转换酶抑制剂卡托普利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。与其他受试制剂和安慰剂相比，1%缬沙坦凝胶的应用促进并显著加快了小鼠的闭合时间，并增加了抗张强度，并在猪模型中得到了验证。1%的缬沙坦凝胶治疗的伤口也表现出较高的线粒体含量，胶原沉积，磷酸化的母亲对decapentaplegic同源物2和3和共同的母亲对decapentaplegic同源物4，α-平滑肌肌动蛋白，CD 31，磷酸化血管内皮生长因子受体2，和p42/44丝裂原活化蛋白激酶。敲除血管紧张素亚型2受体消除了血管紧张素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的作用。
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.