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检索：刘金淑 河南省濮阳市油田总医院
翻译：孔晓明 江苏省溧阳市人民医院
审核：刘金淑 河南省濮阳市油田总医院
陈志锦 广东省东莞市厚街医院
最新的研究显示，用维生素D来加载纳米纤维缝合线可诱导产生抗菌肽。这一发现可能代表了预防手术部位感染的一项重要进展，仅在美国每年就有数十亿美元的需求。
包括俄勒冈州立大学莱纳斯·鲍林研究所的Adrian Gombart在内等合作者使用了同轴静电沉积和轧制工艺，制造成含有25-羟基维生素D3和pam3CSK4肽的缝合线。
肽是由链连接的两个或更多个氨基酸组成的化合物；pam3CSK4的功能是激活细胞toll样受体，继而引发免疫反应，这其中维生素D起关键作用。
研究显示缝合线会持续4周释放25D3，25D3是测试患者维生素D水平时其血液中测量到的形式相似的维生素。缝合线通过初始爆裂释放pam3CSK4，然后持续释放4周。
Gombart表示：“当toll样受体被激活时，会诱导一种特定的酶将25D3转化为其生物活性形式，称为1,25-二羟基维生素D3，由其激活维生素D受体。当活性增加时，维生素D受体靶基因的表达增加，其中一种产生LL-37肽，这种肽能通过破坏微生物膜来杀死微生物。这就是说，如果你受感染了，缝线会激活toll样受体，并开始增加从缝线释放的25D3来产生1,25D3 ，所以在出现局部感染的同时，抗菌肽的产生也增加了”。
该研究的相关作者，内布拉斯加大学医学中心谢经伟(音译)指出，目前使用的抗感染缝合线含有三氯生，即一种在各种消费品中也可以找到的抗细菌真菌剂。他表示：“然而，三氯生的频繁使用会导致细菌的耐药性，它还表现出广泛的健康风险，包括内分泌紊乱、肌肉功能受损、肝脏损伤和癌性肿瘤的发展。与目前可用的产品和治疗方案相比，我们开发的抗感染缝线可以规避多重耐药性选择和其他与健康相关的缺点。新型缝合线也是高度可配置的，可以提供多种生物活性化合物以减少感染风险、优化愈合和减少疤痕。目前没有一种在用的缝合线达到这种功能级别。”
Gombart补充道：“由缝线递送的维生素D也可以影响涉及免疫应答的其他基因以及LL-37。所以像维生素D这样的化合物不仅可以通过抗菌肽靶向细菌，还可以调节其他免疫反应来帮助抵抗感染。针对多个战线有助于减少耐药性的机会”。
这些发现最近在《纳米医学》上发表。
来源：俄勒冈州立大学
原文：
Nanofiber Sutures Promote Production of Infection-Thwarting Peptide
Loading nanofiber sutures with vitamin D induces the production of an infection-fighting peptide, new research shows. The discovery could represent an important advance in the prevention of surgical site infections, a multibillion-dollar challenge each year in the United States alone.
A collaboration that included Adrian Gombart of the Linus Pauling Institute at Oregon State University used coaxial electrospinning deposition and rolling to fabricate sutures that contained 25-hydroxyvitamin D3 and the pam3CSK4 peptide.
A peptide is a compound consisting of two or more amino acids linked in a chain; pam3CSK4's function is to activate a cell's toll-like receptor, which in turn triggers immune responses, in which vitamin D plays a key role.
The research showed the sutures released 25D3 - the same form of the vitamin that's measured in the blood when a patient's vitamin D levels are tested - on a sustained basis over four weeks. The sutures released pam3CSK4 via an initial burst followed by a four-week prolonged release.
"When the toll-like receptor is activated, you induce a particular enzyme to convert 25D3 to its bioactive form, known as 1,25-dihydroxy vitamin D3, that activates the vitamin D receptor," Gombart said. "When activity increases, that increases expression of vitamin D receptor target genes, one of which produces the LL-37 peptide, which kills microbes by disrupting their membranes.
"The idea is, if you were to have an infection, the sutures would activate the toll-like receptors and start increasing production of 1,25D3 from the 25D3 that's being released from sutures - so you get both local induction and an increase in the production of the antimicrobial peptide."
The study's corresponding author, Jingwei Xie of the University of Nebraska Medical Center, notes that the anti-infective sutures currently in use contain triclosan, an antibacterial and antifungal agent also found in a variety of consumer products.
"However, the frequent use has resulted in bacterial resistance," Xie said. "Triclosan also shows a wide range of health risks including endocrine disruption, impaired muscle function, liver damage and the development of cancerous tumors. Compared to the currently available products and treatment options, the anti-infective sutures we develop could circumvent the selection for multidrug resistance and other health-associated shortcomings. The new sutures are also highly configurable and can deliver a variety of bioactive compounds to minimize infection risk, optimize healing and minimize scarring. None of the currently available sutures has this level of function."
Gombart adds that the vitamin D delivered by the sutures could also affect additional genes involved in the immune response as well as LL-37.
"So a compound like vitamin D not only targets bacteria via the antimicrobial peptide, but other immune responses can also be modulated to help combat infection," he said. "Targeting on multiple fronts helps minimize the chance of resistance."
The University of Nebraska Medical Center, the National Institutes of Health, and the Otis Glebe Medical Research Foundation supported this research.
Also involved in the collaboration were researchers from the Joan C. Edwards School of Medicine at Marshall University in Huntington, West Virginia, and the Chongqing Academy of Animal Sciences & Key Laboratory of Pig Industry Sciences in Chongqing, China.
These findings were recently published in Nanomedicine.
Source: Oregon State University
图文：春虾
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发表于 2018-1-17 19:48:51