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11 December 2019 : Laboratory Research  

Shixiang Plaster, a Traditional Chinese Medicine, Promotes Healing in a Rat Model of Diabetic Ulcer Through the receptor for Advanced Glycation End Products (RAGE)/Nuclear Factor kappa B (NF-κB) and Vascular Endothelial Growth Factor (VEGF)/Vascular Cell Adhesion Molecule-1 (VCAM-1)/Endothelial Nitric Oxide Synthase (eNOS) Signaling Pathways

Ji Fei1ABCDEF, Yi-Ming Ling2BCDF, Man-Jie Zeng1BCF, Kai-Wei Zhang1ACDEG*

DOI: 10.12659/MSM.918268

Med Sci Monit 2019; 25:9446-9457

Abstract

BACKGROUND: Shixiang plaster is a traditional Chinese medicine has been used to treat chronic ulcers, including diabetic ulcers. Aminoguanidine is a hydrazine derivative that inhibits the formation of advanced glycosylation end products (AGEs). This study aimed to investigate the effects of shixiang plaster and aminoguanidine on wound healing in the streptozotocin-induced rat model of diabetes and the molecular mechanisms involved.

MATERIAL AND METHODS: Sprague-Dawley rats treated with intraperitoneal streptozotocin and given surgical wounds were divided into the untreated chronic ulcer group (n=10), the aminoguanidine group (n=10), the shixiang plaster group (n=10), and the control group with sham surgery (n=10). Granulation tissue samples underwent light microscopy to evaluate angiogenesis and immunohistochemistry to identify AGE, vascular endothelial growth factor (VEGF), and CD34 expression. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blot measured mRNA and protein expression of receptor for advanced glycation end products (RAGE), vascular cell adhesion molecule-1 (VCAM-1), nuclear factor kappa B (NF-κB) and endothelial nitric oxide synthase (eNOS).

RESULTS: The shixiang plaster group showed a significant increase in angiogenesis in ulcer granulation tissue, significantly reduced expression of AGEs and increased expression of VEGF and CD34 expression in granulation tissue compared with the untreated chronic ulcer group (p<0.05). The shixiang plaster group showed significantly down-regulated expression of RAGE and VCAM-1 compared with the untreated chronic ulcer group (p<0.05). Shixiang plaster promoted angiogenesis by activating the NF-κB p65 associated pathway and eNOS activation.

CONCLUSIONS: Shixiang plaster promoted healing in a rat model of diabetic ulcer through the RAGE/NF-κB and VEGF/VCAM-1/eNOS signaling pathways.

Keywords: Diabetic Angiopathies, Neovascularization, Physiologic, Wound Healing, Wounds and Injuries, Diabetes Complications, Diabetes Mellitus, Experimental, Disease Models, Animal, Drugs, Chinese Herbal, Endothelium, Vascular, Glycation End Products, Advanced, Male, Medicine, Chinese Traditional, NF-kappa B, Nitric Oxide Synthase Type III, Oxidative Stress, Rats, Rats, Sprague-Dawley, Receptor for Advanced Glycation End Products, Signal Transduction, Ulcer, Vascular Cell Adhesion Molecule-1, Vascular Endothelial Growth Factor A

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Medical Science Monitor Basic Research eISSN: 2325-4416
Medical Science Monitor Basic Research eISSN: 2325-4416