Effect Of Transverse Tibial Bone Transport On HIF-1α/VEGF Pathway In Diabetic Foot

Objective:Transverse tibial bone transport(TTT)was carried out in Wanger 3/4 diabetic foot(DF)patients.To observe the clinical efficacy after TTT,and explore the expression of vascular endothelial growth factor(VEGF)and hypoxia-inducible factor 1-alpha(HIF-1α)in gene and protein levels during TTT.And the effect of TTT on Microvessel density(MVD)of DF wound.Further,the effect of TTT on HIF-1α/VEGF signaling pathway and the mechanism of HIF-1α/VEGF signaling pathway in TTT repair of ulcer wounds were clarified,in order to provide effective treatment plan for long-term treatment of DF.Methods:Thirty DF patients who underwent surgery in our department from October 2019to October 2021 were included and randomly divided into two groups,with 15 patients in each group.The experimental group received TTT in addition to conventional treatment and the control group received conventional treatment.Granulation tissue was collected from ulcer 1 day before surgery and 4 and 7 weeks after surgery for each patient in the experimental group,with a size of 8x8x3 mm.In the control group,wound samples were taken at the same time point.The postoperative skin temperature,ABI,VAS and healing days were compared between the two groups.The expression levels of HIF-1α and VEGF were quantitatively analyzed by q RT-PCR and WB,and the MVD in DF wound tissue was evaluated by immunohistochemistry.Results:1.TTT treatment of Wagner3/4 grade DF was better than conventional treatment in improving VAS,ABI,skin temperature and accelerating wound healing,and the differences were statistically significant,P values were all less than 0.05.Ulcer wounds healed after treatment in both groups,with 68.27±7.75 days in the experimental group and82.27±7.60 days in the control group.2.HIF-1α m RNA and VEGF m RNA were expressed in both DF wound tissues,and the expression levels of HIF-1α m RNA and VEGF m RNA in both groups showed a trend of first increasing and then decreasing.Comparing HIF-1αm RNA and VEGF m RNA at the same sampling time point between the two groups,the results showed that the P value of sampling 1 day before surgery was greater than 0.05,no significant difference,and the P value of sampling 4 weeks and 7 weeks after surgery was less than 0.01,significant difference;the comparison of HIF-1α m RNA and VEGF m RNA in the two groups at different sampling time points showed that the P value was less than 0.01,and the difference was statistically significant.3.The expression levels of HIF-1α protein and VEGF protein in DF wound tissue of experimental group and control group showed a trend of increasing to decreasing.The comparison of HIF-1α protein and VEGF protein between the two groups at the same sampling time point showed that the P value of the two groups was greater than 0.05 1 day before surgery,and no significant difference,while the P value of the two groups was less than 0.01 4 weeks and 7 weeks after surgery,significant difference;the comparison of HIF-1α protein and VEGF protein in the two groups at different sampling time points showed that P values were all less than 0.01,indicating statistical differences.4.The staining count of vascular endothelial cells in both the experimental group and the control group increased first and then decreased.The comparison of MVD count between the two groups at the same sampling time point showed that P value was greater than 0.05 in the 1 day before surgery,but P value was less than 0.01 in the 4 and7 weeks after surgery,indicating a statistical difference;the comparison of MVD counts in the two groups at different sampling time points showed that P values were all less than 0.01,indicating statistical differences.Conclusion: 1.Both TTT technology and debridement and dressing therapy can stimulate the regeneration of distal ischemic necrotic tissue of DF patients and promote the repair of diabetic foot ulcers(DFU),but TTT technology has better performance in improving skin temperature,relieving pain,improving blood flow and accelerating wound healing.2.TTT technology may promote angiogenesis,rebuild local microcirculation,and repair refractory ulcers by increasing gene and protein expression levels of HIF-1α and VEGF.3.HIF-1α/VEGF signaling pathway is activated during bone transport,and its mediated repair and regeneration is crucial for the treatment of DF.