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Effect of regulating expression of matrix metalloproteinase by topical application of insulin on angiogenesis of diabetic wounds

CHANG Qing-xuan, YANG Pei-lang, LIU Yan, ZHANG Xiong   

  1. Department of Burn and Plastic Surgery， Ruijin Hospital， Shanghai Jiao Tong University School of Medical, Shanghai 200025, China
  • Online:2015-09-28 Published:2015-09-30
  • Supported by:

    National Natural Science Foundation of China, 81170761， 81270909

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Abstract:

Objective  To investigate the regulation of vascular endothelial growth factor (Vegf) and matrix metalloproteinase 2/9 (Mmp-2/9) by topical application of insulin and explore the effects of Vegf and Mmp-2/9 on promoting the angiogenesis of diabetic wounds and their correlation. Methods  The diabetes of 60 Wistar rats were induced by multiple intraperitoneal injections with a low dose of streptozocin (STZ) after high-fat diet feeding. After 5 weeks, four full-thickness skin wounds with the diameter of 0.9 cm were made on the back of rats. Two wounds were treated with 20 μL saline (saline group) and insulin of 0.1 U/20 μL saline (insulin group) in diagonal form each day until complete healing. The healing speed of wounds was observed and recorded and samples were harvested on 3, 7, 13, and 21 d. The structure of skin tissues of healed wounds and angiogenesis of wounds on 7 and 13 d were observed by H-E staining. The mRNA expressions of Vegf, Vegfr-2, and Mmp-2/9 were detected by real-time PCR. Results  Compared with the saline group, the healing speed of the insulin group was faster and the difference between two groups was statistically significant (P<0.05). The number of spikes in the epidermis of insulin group was larger than that of the saline group on 21 d after wounds were healed and dermal tissues were denser. The number of angiogenic blood vessel of the insulin group was larger than that of the saline group on 7 and 13 d. The mRNA expressions of Vegf, Vegfr-2, and Mmp-2/9 of the insulin group increased progressively on 3, 7, and 13 d, reached peak on 13 d, and then decreased. The mRNA expressions of Vegf and Vegfr-2 were still higher than those of the saline group on 21 d and the  mRNA expression of Mmp-2/9 decreased. The difference between two groups was statistically significant (P<0.05). Conclusion  Topical application of insulin promotes the up-regulation of mRNA expressions of Vegf and Vegfr-2, regulates the mRNA expression of Mmp-2/9, and promotes the angiogenesis of diabetic wounds.

Key words: insulin, diabetes, angiogenesis, Vegf, Mmp-2, Mmp-9