Effect of Cycloastragenol on Wound Healing of Diabetic Skin Ulcers in Rats Based on Wnt/β-catenin Pathway
Objective:To investigate the effect of Cycloastragenol(CAG)on wound healing and its mechanism in a rat model of diabetic skin ulcer.Methods:The rats were divided into control group,model group,CAG 20 mg/kg group,CAG 20 mg/kg+IWR-1(Wnt pathway inhibitor)8.2 μg/kg group,and CAG 20 mg/kg+STF-31(GLUT1 inhibitor)5.8 mg/kg group.Except for the control group,all other rats were injected intraperitoneally with streptozotocin to establish diabetes model,and the marked skin and subcutaneous tissue on rat back were removed to es-tablish skin ulcer model.The rats were orally administered with corresponding drugs for 14 days,and wound healing rates were measured on the 5th,10th,and 14th days.Serum contents of superoxide dismutase(SOD),malondialdehyde(MDA),and reduced glutathione(GSH)were assessed.HE staining was used to detect pathological changes in the wound granulation tissue,and immunohistochemistry was used to examine the expressions of vascular endothelial growth factor A(VEGFA)and endothelial-type nitric oxide synthase(ENOS).The effect of CAG on human umbilical vein endothelial cell(HUVEC)migration during LPS-induced inflammation was measured by cell scratch assay.Western blot was used to analyze the protein expressions of[3-catenin,glycogen synthase kinase-3β[3(GSK-3β),R-spondin3(RSPO3),G1/S-specific Cyclin-D1,Matrix Metalloproteinase-2(MMP2),and Matrix Metalloproteinase-9(MMP9)in wound granulation tissues on 10th day of administration and LPS induced HUVEC cells.Results:Compared with control group,the wound healing rate was significantly reduced on the 5th and 10th day of administration in model group(P＜O.01),the ENOS expression and serum content of SOD were significantly reduced(P＜0.05 or P＜0.01),while serum content of MDA was significantly increased(P＜0.01).On the 10th day of administration,the protein expressions of β-catenin,cyclinD1 and MMP2 were significantly down regulated(P＜0.01).Compared with model group,the wound healing rate in CAG 20mg/kg group was significantly increased on the 10th day(P＜0.01),the serum content of SOD and ENOS expression in wound granulation tissue were significantly increased on the 5th and 10th day of administration(P＜0.01),the protein expressions of β-catenin,cy-clinD1and MMP2 were significantly up regulated(P＜0.05 or P＜0.01).Compared with control group,the cell migration rate was significant-ly reduced in model group(P＜0.05 orP＜0.01),the protein expressions of cyclinD1,MMP2 and MMP9 were down regulated(P＜0.01).Compared with model group,the cell immigration rate in CAG 25 μg/mL group was increased(P＜O.05 or P＜0.01),while the protein ex-pressions of cyclinD1 and MMP9 were up regulated(P＜0.01).Conclusion:CAG can promote wound healing in diabetic skin ulcer model rats,and its mechanism may be related to the activation of the Wnt/β-catenin signaling pathway.
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