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OBJECTIVE To explore the effects of pterostilbene （PTE） on wound healing in diabetic skin ulcer model rats and its mechanism. METHODS Ten SD rats were grouped into control group； after diabetic skin ulcer model of other rats was induced by giving high-fat and high-sugar diet+intraperitoneal injection of streptozotocin+cutting off the skin and subcutaneous tissue in the marked area of the back， model rats were randomly divided into model group， PTE low-dose group （40 mg/kg）， PTE high-dose group （80 mg/kg）， PTE high-dose+PP2 group （80 mg/kg PTE+2 mg/kg SRC inhibitor PP2）， with 10 rats in each group. On the second day after modeling， the rats in each drug group were intraperitoneally injected with corresponding drug solutions， while the rats in control group and model group were intraperitoneally injected with normal saline， once a day， for 14 consecutive days. The wound healing rate of rats in each group was measured on the 7th and 14th day of administration； the contents of interleukin-1β （IL-1β）， IL-6， tumor necrosis factor-α （TNF-α） and vascular endothelial growth factor （VEGF） in the serum of rats were detected； the pathological changes of wound granulation tissue were observed， and the expressions of SRC/mitogen-activated protein kinase kinase （MEK）/extracellular signal-regulated kinase （ERK） signaling pathway-related proteins in wound granulation tissue were detected. RESULTS Compared with control group， the wound healing rate， serum content of VEGF， the phosphorylation levels of SRC， MEK1/2 and ERK1/2 were decreased significantly （P＜0.05）， while serum contents of IL- 1β， IL-6 and TNF-α were increased significantly （P＜0.05）； there was obvious infiltration of inflammatory cells in the wound granulation tissue， and the number of new blood vessels decreased. Compared with model group， above indexes of PTE low-dose and high-dose groups were improved significantly （P＜0.05）， and the pathological injury of granulation tissue in wound was improved. PP2 significantly reversed the improvement effects of PTE on the above indexes （P＜0.05）. CONCLUSIONS PTE can promote the wound healing of diabetic skin ulcer model rats， the mechanism of which may be related to activating SRC/MEK/ERK signaling pathway.
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Objective:To study the effect of graphene oxide (GO) on adipose-derived mesenchymal stem cells (Ad-MSCs) to promote diabetic skin wound healing.Methods:Ad-MSCs were cultured with GO at concentration of 100, 200, and 400 μg/mL and with 25 mmol/L of glucose for 48 h. The apoptosis of Ad-MSCs was detected by flow cytometry and Western blotting. Eighteen BALB/c thymus free female nude mice were selected to establish the skin defect model of diabetic nude mice. Then phosphate-buffered saline, Ad-MSCs, and GO+ Ad-MSCs were injected into the damaged skin of nude mice by intradermal injection for treatment, thereby created the control group, Ad-MSCs group, and GO+ Ad-MSCs group, 6 mice each group. The survival of wound cells and skin healing of mice were observed after surgery, and the wound healing was determined by HE staining and Masson staining.The level of epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), tumor necrosis factor-α (TNF-α), and interleukin 6 (IL-6) were determined by enzyme-linked immunosorbent assay (ELISA).Results:Compared with the high glucose group without GO(control group), the apoptosis rate of Ad-MSCs co-culture with GO was significantly reduced( P<0.05), and the apoptosis rate decreased with the increase of GO concentration. The expression level of Bax protein decreased, and the expression level of Bcl-2 protein increased ( P<0.05). Diabetic skin defect model showed that the survival rate of Ad-MSCs and wound healing degree in GO+ Ad-MSCs group were significantly increased ( P<0.05), and the degree of epithelialization and thickness of collagen regeneration were better than those in other groups. ELISA results showed that the expressions of EGF and VEGF were significantly increased in GO+ Ad-MSCs group ( P<0.05), while the expressions of TNF-α and IL-6 were significantly decreased ( P<0.05). Conclusion:GO can inhibit the apoptosis of Ad-MSCs in vitro. In vivo, Ad-MSCs treated with GO have higher survival rate, faster wound healing, and better effect than Ad-MSCs treated alone.
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Objective To investigate the protective effect of geniposide against diabetic rats with skin ulcer and the mechanism.Methods Rats were divided into a normal group,model group,and geniposide subgroups(Gen(L):200 mg/kg;Gen(H):500 mg/kg).Diabetic rats were treated with normal saline or geniposide by intragastric administration(n=6).Treatments were administered once a day,and the wound healing and inflammation of each group were recorded every day.After 7 days of treatment for diabetic skin ulcers,the wound area,tissue sections,TUNEL staining and Western blot were used to quantitatively analyze changes in wound healing,apoptosis,and related regulatory protein expression.Results Compared with the model group,the group receiving orally administered geniposide(200 and 500 mg/kg)showed significantly improved wound healing and increased contraction of the injured area.In terms of skin wound apoptosis in diabetic rats,TUNEL-positive cells were significantly reduced in geniposide subgroups(P<0.05).Geniposide significantly inhibited skin inflammation and promoted wound repair,which may be related to promotion of PI3K and Akt phosphorylation.Conclusions Geniposide promoted skin wound repair in diabetic rats by inhibiting inflammatory responses and apoptosis.
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BACKGROUND: Diabetes is characterized by chronic hyperglycemia, and hyperglycemia can increase reactive oxygen species (ROS) production from the mitochondrial electron transport chain. The formation of ROS in cells induces oxidative stress and activates oxidative damage-inducing genes. There is no research on the protein levels of oxidative damage-related genes AKR1C3 in human diabetic skin. We explored the expression of AKR1C3 in diabetic skin compared with normal skin tissue. OBJECTIVE: To compare the expression of AKR1C3 in normal skin versus diabetic skin. METHODS: AKR1C3 expression was evaluated by western blotting in 6 diabetic skin tissue samples and 6 normal skin samples. Immunohistochemical staining was carried out to analyze AKR1C3 expression in the 6 diabetic skin tissue samples (July 2009 to December 2011; Department of Plastic and Reconstructive Surgery at Soonchunhyang University Seoul Hospital, Seoul, Korea). RESULTS: The western blotting showed a significant reduction in AKR1C3 protein expression in diabetic skin tissue compared to normal tissue. Immunohistochemical examination of AKR1C3 showed that it was weakly expressed in all diabetic skin samples. CONCLUSION: We believe that AKR1C3 is related to diabetic skin in altered metabolic states which elevate ROS production.