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抗衰老小分子二甲双胍促进慢性皮肤愈合
来源: | 作者:赵盼 | 时间 :2018-04-09 | 1124 次浏览 | 分享到:

皮肤愈合困难在衰老个体中尤其常见,我们发现局部使用二甲双胍能够促进皮肤愈合,包括年轻和年老的皮肤,我们希望二甲双胍的这种效应能够应用到临床,解决更多由于衰老引起的皮肤愈合问题

皮肤是人体最大的组织器官,一旦受到伤害要经历漫长的愈合周期,慢性愈合问题甚至会导致皮肤的结构和功能受损。衰老所引起的是皮肤慢性愈合最为常见,但是目前为止没有很好地治疗手段。卡路里限制是临床上所能实施的最好办法,很多小分子化合物发挥作用的药理就是依靠卡路里限制,其中二甲双胍、白藜芦醇、雷帕霉素是最为常见的,所以我们以这三种小分子作为研究对象。虽然三种小分子都具有限制卡路里的作用,但是我们发现只有二甲双胍能够在皮肤愈合方便发挥显着的疗效,由于考虑到系统用药可能产生的副作用,我们局部用药的方式,既避免了副作用的产生又方便易操作,很适用于临床的应用。

题目:Anti-aging pharmacology in cutaneous wound healing: effects of metformin, resveratrol, and rapamycin by local application

作者:Pan Zhao, ? Bing-Dong Sui, ? Nu Liu, ? Ya-Jie Lv, Chen-Xi Zheng, Yong-Bo Lu, Wen-Tao Huang, Cui-Hong Zhou, Ji Chen, Dan-Lin Pang, Dong-Dong Fei, Kun Xuan, Cheng-Hu Hu*?and?Yan Jin*

单位:1.State Key Laboratory of Military Stomatology & National Clinical Research?Center for Oral Diseases & Shaanxi International Joint Research Center for?Oral Diseases, Center for Tissue Engineering, School of Stomatology, Fourth?Military Medical University, Xi’an, Shaanxi 710032, China

2 Xi’an Institute of Tissue Engineering and Regenerative Medicine, Xi’an,?Shaanxi 710032, China

3 Research and Development Center for Tissue Engineering, Fourth Military?Medical University, Xi’an, Shaanxi 710032, China

4 Department of Periodontology, Stomatological Hospital, Zunyi Medical?College, Zunyi, Guizhou 563003, China

5 Department of Dermatology, Tangdu Hospital, Fourth Military Medical?University, Xi’an, Shaanxi 710069, China

摘要:Cutaneous wounds are among the most common soft tissue?injuries and are particularly hard to heal in aging. Caloric?restriction (CR) is well documented to extend longevity; pharmacologically, profound rejuvenative effects of CR mimetics have?been uncovered, especially metformin (MET), resveratrol (RSV),?and rapamycin (RAPA). However, locally applied impacts and?functional differences of these agents on wound healing remain?to be established. Here, we discovered that chronic topical?administration of MET and RSV, but not RAPA, accelerated?wound healing with improved epidermis, hair follicles, and?collagen deposition in young rodents, and MET exerted more?profound effects. Furthermore, locally applied MET and RSV?improved vascularization of the wound beds, which were?attributed to stimulation of adenosine monophosphate-activated?protein kinase (AMPK) pathway, the key mediator of wound?healing. Notably, in aged skin, AMPK pathway was inhibited,?correlated with impaired vasculature and reduced healing ability.?As therapeutic approaches, local treatments of MET and RSV?prevented age-related AMPK suppression and angiogenic inhibition in wound beds. Moreover, in aged rats, rejuvenative effects?of topically applied MET and RSV on cell viability of wound beds

were confirmed, of which MET showed more prominent anti-aging effects. We further verified that only MET promoted?wound healing and cutaneous integrity in aged skin. These?findings clarified differential effects of CR-based anti-aging?pharmacology in wound healing, identified critical angiogenic?and rejuvenative mechanisms through AMPK pathway in both?young and aged skin, and unraveled chronic local application of?MET as the optimal and promising regenerative agent in treating?cutaneous wound defects.

文章链接:PMID: 28677234

??????????https://www.ncbi.nlm.nih.gov/pubmed/28677234


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