2022, Vol. 26 ›› Issue (20): 3196-3201

Shixiang Paste interferes with the expression of advanced glycation endproducts and its receptors and endothelial nitric oxide synthase in wound tissue of diabetic ulcer rats

Fei Ji1, Zhang Kaiwei1, Zhou Yifu2, Ling Yiming2   

Abstract: BACKGROUND: Diabetic ulcer, as one of the common complications of diabetes, has caused serious harm to human health due to its low healing rate and high amputation rate. Although traditional Chinese medicine has been proved to improve wound healing, the molecular mechanism of this effect has not been clarified.
OBJECTIVE: To investigate the possible mechanism of Shixiang Paste in treating diabetic ulcers.
METHODS: Forty clean male Sprague-Dawley rats were randomly divided into four groups (n=10 per group): a normal control group, a diabetic ulcer group, a cell growth factor group and a Shixiang Paste group. Except for the normal control group, a diabetic rat model was established in the other three groups. After 1 week, an ulcer wound model was established in four groups by using the full-thickness skin defect method. One week after successful modeling, rats in the Shixiang Paste and cell growth factor groups were treated with external Shixiang Paste and cell growth factor, respectively. Wounds in the diabetic ulcer and normal control groups were only covered and fixed with double sterile dry gauze. The granulation tissue samples were taken from the wound on the back of rats on the 7th and 14th days after intervention. Western blot was used to detect the protein expression of receptors of advanced glycation endproducts and endothelial nitric oxide synthase in the granulation tissue from the back wound of rats. Hematoxylin-eosin staining was used to detect pathological changes in rat back wound samples. Immunohistochemical staining was used to detect the expression of advanced glycation endproducts in the granulation tissue from the wound on the back of rats.
RESULTS AND CONCLUSION: The results of hematoxylin-eosin staining showed that large areas of unrepaired tissue were seen under the microscope in the normal control group and the diabetic ulcer group on the 7th and 14th days after intervention, while in the Shixiang Paste and cell growth factor groups, the wounds healed well on the 7th and 14th days after intervention. Western blot results showed that, compared with the normal control group, the expression of receptors of advanced glycation endproducts was decreased in the diabetic ulcer group was increased, and the expression of endothelial nitric oxide synthase (P < 0.05). In addition, the expression of receptors of advanced glycation endproducts was relatively decreased, and the expression of endothelial nitric oxide synthase was relatively increased in the Shixiang Paste group and cell growth factor group (P < 0.05). Compared with the diabetic ulcer group, the expression of receptors of advanced glycation endproducts was relatively decreased, and the expression of endothelial nitric oxide synthase was relatively increased in the Shixiang Paste group and the cell growth factor group (P < 0.05). Compared with the cell growth factor group, the expression of receptors of advanced glycation endproducts was relatively decreased, and the expression of endothelial nitric oxide synthase was relatively increased in the Shixiang Paste group (P < 0.05). The results of immunohistochemical staining showed that, compared with the normal control group, the expression of advanced glycation endproducts was increased in the diabetic ulcer group and the cell growth factor group, and the expression of advanced glycation endproducts was decreased in the Shixiang Paste group (P < 0.05). Compared with the diabetic ulcer group, the expression of advanced glycation endproducts was increased in the other groups (P < 0.05). Compared with the Shixiang Paste group, the expression level of advanced glycation endproducts was decreased in the cell growth factor group (P < 0.05). To conclude, Shixiang Paste can promote the repair of diabetic ulcer wound. Inhibiting the expression of advanced glycation endproducts and receptors and enhancing the expression of endothelial nitric oxide synthase in wound tissue may be one of the mechanisms.
Key words: Shixiang Paste, diabetic ulcer, advanced glycation endproduct, receptor of advanced glycation endproduct, endothelial nitric oxide synthase