Carnosine enhances diabetic wound healing in the db/db mouse model of type 2 diabetes
Carnosine enhances diabetic wound healing in the db/db mouse model of type 2 diabetes
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DOI：
10.1007/s00726-012-1269-z
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发表时间：
2012-07-01
期刊：
影响因子：
3.5
通讯作者：
Forsberg, Elisabete Alcantara
中科院分区：
文献类型：
--
作者：
Ansurudeen, Ishrath;Sunkari, Vivekananda Gupta;Forsberg, Elisabete Alcantara
糖尿病（DM）是一种具有严重晚期并发症的进行性疾病。正常的伤口愈合涉及由多种因素决定的一系列复杂且精心策划的分子事件。在糖尿病中，伤口愈合由于在伤口愈合的所有阶段的缺陷和失调的细胞和分子事件而严重受损，导致无法愈合的慢性伤口。肌肽是一种丙氨酸和组氨酸的二肽，是一种内源性抗氧化剂，被证明可以加速伤口和溃疡的愈合。然而，对其在糖尿病伤口愈合中的作用知之甚少。因此，我们研究了肌肽在db/db小鼠（2型DM的小鼠模型）中的伤口愈合中的作用。在db/db小鼠中制造6毫米圆形伤口，并每隔一天分析伤口愈合。将肌肽（100 mg/kg）注射（I. P.）每天，也适用于当地。用肌肽治疗显著增强伤口愈合，并且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。人皮肤成纤维细胞和微血管内皮细胞的体外研究表明，肌肽在高葡萄糖存在下增加细胞活力。这些作用，除了其作为抗氧化剂和组胺合成前体的已知作用之外，还为肌肽在糖尿病伤口愈合中的可能治疗用途提供了证据。
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.