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Abstract：
Cutaneous wounds, both acute and chronic, begin with loss of the integrity, and thus barrier function, of the skin. Surgery and trauma produce acute wounds. There are 22 million surgical procedures per year in the United States alone, based on data from the American College of Surgeons, resulting in a prevalence of 6.67%. Acute traumatic wounds requiring repair total 8 million per year, 2.42% or 24.2 per 1000. The cost of wound care is increasing; it approached USD 100 billion for just Medicare in 2018. This burden for wound care will continue to rise with population aging, the increase in metabolic syndrome, and more elective surgeries. To heal a wound, an orchestrated, evolutionarily conserved, and complex series of events involving cellular and molecular agents at the local and systemic levels are necessary. The principal factors of this important function include elements from the neurological, cardiovascular, immune, nutritional, and endocrine systems. The objectives of this review are to provide clinicians engaged in wound care and basic science researchers interested in wound healing with an updated synopsis from recent publications. We also present data from our primary investigations, testing the hypothesis that cannabidiol can alter cutaneous wound healing and documenting their effects in wild type (C57/BL6) and db/db mice (Type 2 Diabetes Mellitus, T2DM). The focus is on the potential roles of the endocannabinoid system, cannabidiol, and the important immune-regulatory wound cytokine IL-33, a member of the IL-1 family, and connective tissue growth factor, CTGF, due to their roles in both normal and abnormal wound healing. We found an initial delay in the rate of wound closure in B6 mice with CBD, but this difference disappeared with time. CBD decreased IL-33 + cells in B6 by 70% while nearly increasing CTGF + cells in db/db mice by two folds from 18.6% to 38.8% (p < 0.05) using a dorsal wound model. We review the current literature on normal and abnormal wound healing, and document effects of CBD in B6 and db/db dorsal cutaneous wounds. CBD may have some beneficial effects in diabetic wounds. We applied 6-mm circular punch to create standard size full-thickness dorsal wounds in B6 and db/db mice. The experimental group received CBD while the control group got only vehicle. The outcome measures were rate of wound closure, wound cells expressing IL-33 and CTGF, and ILC profiles. In B6, the initial rate of wound closure was slower but there was no delay in the time to final closure, and cells expressing IL-33 was significantly reduced. CTGF + cells were higher in db/bd wounds treated with CBD. These data support the potential use of CBD to improve diabetic cutaneous wound healing.
摘要：
皮肤伤口,急性和慢性，从完整性的丧失开始，因此屏障功能，的皮肤。手术和创伤产生急性创伤。仅在美国，每年就有2200万例外科手术，根据美国外科医生学院的数据，患病率为6.67%。每年需要修复的急性创伤总计800万件，2.42%或24.2/1000。伤口护理的成本正在增加；2018年，仅Medicare就接近1000亿美元。随着人口老龄化，伤口护理的负担将继续增加，代谢综合征的增加，和更多的选择性手术。为了治愈伤口，精心策划的，进化保守，和复杂的一系列事件涉及细胞和分子在局部和全身水平是必要的。这一重要功能的主要因素包括来自神经系统的元素，心血管,免疫，营养,和内分泌系统。这篇综述的目的是为从事伤口护理的临床医生和对伤口愈合感兴趣的基础科学研究人员提供最新出版物的最新概要。我们还提供了主要调查的数据，测试大麻二酚可以改变皮肤伤口愈合的假设，并记录其在野生型（C57/BL6）和db/db小鼠中的作用（2型糖尿病，T2DM）。重点是内源性大麻素系统的潜在作用，大麻二酚,和重要的免疫调节伤口细胞因子IL-33，IL-1家族的成员，和结缔组织生长因子，CTGF,由于它们在正常和异常伤口愈合中的作用。我们发现有CBD的B6小鼠的伤口闭合速率最初延迟，但是这种差异随着时间的推移而消失了。使用背侧创伤模型,CBD使B6中的IL-33+细胞减少70%,同时使db/db小鼠中的CTGF+细胞从18.6%增加两倍至38.8%(p<0.05)。我们回顾了目前关于正常和异常伤口愈合的文献，并记录CBD在B6和db/db背侧皮肤伤口中的作用。CBD可能对糖尿病伤口有一些有益作用。我们应用6mm圆形冲头在B6和db/db小鼠中创建标准尺寸的全厚度背侧伤口。实验组接受CBD，而对照组仅接受载体。结果指标是伤口闭合率，表达IL-33和CTGF的伤口细胞，和ILC配置文件。在B6中，伤口闭合的初始速度较慢，但最终闭合的时间没有延迟，表达IL-33的细胞显著减少。在用CBD处理的db/bd伤口中CTGF+细胞更高。这些数据支持CBD改善糖尿病皮肤伤口愈合的潜在用途。
