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2022, Vol. 26 ›› Issue (5): 724-729Deep seawater promotes wound healing in diabetic mice by activating PI3K/Akt pathwayLi Weiming, Xu Qingwen, Li Yijun, Sun Yanbo, Cui Jin, Xu Pengyuan
Abstract: BACKGROUND: Preliminary studies have confirmed that deep seawater not only affects the tolerance and immunity of mice, but also has an important regulatory effect on wound repair. OBJECTIVE: To explore the effect of deep seawater on the PI3K/Akt pathway in the process of wound repair in diabetic mice. METHODS: Forty-eight Kunming mice were enrolled to establish a diabetes model. A 1 cm2 wound was made on the back after successful modeling, and all the mouse models were randomized into four groups for corresponding treatments, including drinking purified water (control), tap water, deep seawater and deep seawater+LY294002, with 12 rats in each group. On the 3rd, 7th, and 10th days after wound modeling, the wound healing was observed, and western blot was used to detect the expression levels of vascular endothelial growth factor, basic fibroblast growth factor, hypoxia-inducible factor 1α, p-PI3K, p-Akt, PI3K and Akt in the wound tissue. qRT-PCR and western blot were used to detect the expression levels of collagen type I, collagen type III, interleukin-1β, tumor necrosis factor-α and transforming growth factor-β1 mRNA. On the 3rd and 10th days after wound modeling, hematoxylin-eosin staining was used to observe the morphological changes of the wound. The study protocol was approved by the Animal Ethic Committee of Kunming Institute of Zoology, Chinese Academy of Science with an approval No. KPRC-2017091. RESULTS AND CONCLUSION: The wound healing rate of the deep seawater group was higher than that of the control group and the tap water group (P < 0.01), while there was no significant difference in the wound healing rate between the tap water group and deep seawater+LY294002 group (P > 0.05). Hematoxylin-eosin staining showed that there were a large number of inflammatory cells infiltrated and a few fibroblasts on the wound surface in the control group, tap water group, and deep seawater+LY294002 group on the 3rd day, and granulation tissue, capillaries and fibroblasts were visible on the 10th day. In the deep seawater group, fibroblasts, capillaries and a few inflammatory cells were seen on the 3rd day, and new granulation tissue, more collagen fibers and a few capillaries were seen on the 10th day. Western blot analysis showed that the expressions of vascular endothelial growth factor, basic fibroblast growth factor, hypoxia-inducible factor 1α, p-PI3K and p-Akt in the deep seawater group were higher than those in the control group and the tap water group on each observational time point (P < 0.01). qRT-PCR and western blot results showed that the expressions of collagen type I, collagen type III and transforming growth factor-β1 in the deep seawater group were higher than those in the control group and deep seawater+LY294002 group on each observational time point (P < 0.05 or P < 0.01), while the expression levels of interleukin-1β and tumor necrosis factor-α were lower than those in the control group and deep seawater+LY294002 group (P < 0.05 or P < 0.01). To conclude, deep seawater can promote wound healing in diabetic mice via activating the PI3K/Akt pathway. Key words:diabetics mellitus, PI3K/Akt pathway, deep seawater, wound healing, experimental animal |