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肌肽可增强 2 型糖尿病 db/db 小鼠模型的糖尿病伤口愈合。

Carnosine enhances diabetic wound healing in the db/db mouse model of type 2 diabetes.

机构信息

Department of Molecular Medicine and Surgery, Rolf Luft Centrum, Karolinska Institutet, Stockholm, Solna, Sweden.

出版信息

Amino Acids. 2012 Jul;43(1):127-34. doi: 10.1007/s00726-012-1269-z. Epub 2012 Mar 24.

DOI:10.1007/s00726-012-1269-z
PMID:22451275
Abstract

Diabetes mellitus (DM) is a progressive disorder with severe late complications. Normal wound healing involves a series of complex and well-orchestrated molecular events dictated by multiple factors. In diabetes, wound healing is grossly impaired due to defective, and dysregulated cellular and molecular events at all phases of wound healing resulting in chronic wounds that fail to heal. Carnosine, a dipeptide of alanine and histidine and an endogenous antioxidant is documented to accelerate healing of wounds and ulcers. However, not much is known about its role in wound healing in diabetes. Therefore, we studied the effect of carnosine in wound healing in db/db mice, a mice model of Type 2 DM. Six millimeter circular wounds were made in db/db mice and analyzed for wound healing every other day. Carnosine (100 mg/kg) was injected (I.P.) every day and also applied locally. Treatment with carnosine enhanced wound healing significantly, and wound tissue analysis showed increased expression of growth factors and cytokines genes involved in wound healing. In vitro studies with human dermal fibroblasts and microvascular-endothelial cells showed that carnosine increases cell viability in presence of high glucose. These effects, in addition to its known role as an antioxidant and a precursor for histamine synthesis, provide evidence for a possible therapeutic use of carnosine in diabetic wound healing.

摘要

糖尿病(DM)是一种进展性疾病,伴有严重的晚期并发症。正常的伤口愈合涉及一系列由多种因素决定的复杂且协调良好的分子事件。在糖尿病中,由于在伤口愈合的所有阶段都存在细胞和分子事件的缺陷和失调,导致伤口愈合严重受损,从而导致慢性伤口无法愈合。肌肽是一种由丙氨酸和组氨酸组成的二肽,是一种内源性抗氧化剂,已被证明可加速伤口和溃疡的愈合。然而,关于它在糖尿病伤口愈合中的作用,我们知之甚少。因此,我们研究了肌肽对 2 型糖尿病模型 db/db 小鼠伤口愈合的影响。在 db/db 小鼠身上制造了 6 毫米的圆形伤口,每隔一天分析一次伤口愈合情况。每天(IP)注射肌肽(100mg/kg)并局部应用。肌肽治疗可显著促进伤口愈合,伤口组织分析显示参与伤口愈合的生长因子和细胞因子基因的表达增加。体外研究人类真皮成纤维细胞和微血管内皮细胞表明,肌肽在高葡萄糖存在下可增加细胞活力。除了其作为抗氧化剂和组氨酸合成前体的已知作用外,这些作用为肌肽在糖尿病伤口愈合中的可能治疗用途提供了证据。

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