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Effect Of Transverse Tibial Bone Transport On Colony Forming Of Hematopoietic Stem Celland PI3K/AKT Signaling Pathway In Diabetic Foot

Posted on:2019-11-04Degree:MasterType:Thesis
Country:ChinaCandidate:J XiangFull Text:PDF
GTID:2394330545980480Subject:Endocrine
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Background Diabetic foot is one of the serious chronic complications of diabetic patients.It is characterized by high incidence,huge cost,difficult treatment and poor curative effect.Severe cases usually need amputation.At present,the treatment of diabetic foot includes debridement,anti infection and revascularization,among which the reconstruction of lower limb blood is essential.The existing internal medicine,surgical intervention,arterial bypass grafting and stem cell transplantation can improve the blood supply of the lower limbs,but each has its limitations.Some patients still end up with amputation.Therefore,a new safer and more effective means of revascularization is needed clinically.The transverse tibial bone transport is based on the principle of tension stress,which makes the biological tissue stimulate regeneration and repair by sustained slow traction.A large number of studies have confirmed that bone removal can improve the microcirculation of the traction area significantly,the blood supply is obviously increased,and the effect of blood transport reconstruction is good.Our team has applied the technique of lateral tibial bone transfer to treat diabetic foot above Wagner3 level in 181 cases,and achieved satisfactory ulcer healing and limb salvage.It was found that there was a distance between the moving part and the wound of diabetic foot,and the healing of bilateral limb ulcers after unilateral bone removal in some patients showed that it might be related to mobilizing the bone marrow stem cells to migrate to the wound to promote the healing.Bone marrow stem cells include mesenchymal stem cells,hematopoietic stem cells,endothelial progenitor cells,etc.In semisolid culture medium,single progenitor cells,also known as colony forming cells,can count and evaluate hematopoietic stem cells and other bone marrow stem cells by colony forming cell detection.A large number of studies indicate that SDF-1/CXCR4 axis can promote the survival and migration of stem cells to damaged tissues and regeneration,and downstream signaling pathway PI3K/AKT plays a key role in regulating stem cells homing to wound tissues.At present,the treatment of tibia transversal bone removal is a major clinical report,and its internal mechanism is less reported.It is very worthy of further study.Objectives To observe hematopoietic stem cell colony formation of diabetic foot patients before and after transverse tibial bone transport.Using real-time fluorescence quantitative PCR detection of relative expression of PI3K/AKT signal pathway of diabetic foot patients before and after transverse tibial bone transport.Discusse the mechanism of mobilization of stem cells in the repair of diabetic foot bone transport.MethodsFrom 2016 to 2017 in 20 cases of diabetic foot patients in the First Affiliated Hospital of Guangxi Medical University joint surgery for the treatment of transverse tibial bone transport(Wagner3-4),not using immunosuppressive drugs,corticosteroids and other drugs.Peripheral venous blood was collected from patients before and after bone removal.Separate peripheral blood mononuclear cells by density gradient centrifugation,observe the changes of the colony formation of hematopoietic stem cells,and the relative expression of PI3K/AKT signaling pathway change detection by real-time fluorescence quantitative PCR technology.SPSS 22.0 was used for statistical analysis and OriginPro 8.5 was used for plotting.Mean±standard deviation(~—x±s)was described,and paired t test was used for mean comparison.P<0.05 was statistically significant.ResultsThe number of Hematopoietic stem cell colony formation was significantly increased after transverse tibial bone transport one month compared with preoperative,burst forming unit-erythroid count:(74.95±9.63)vs(46.20±7.43),t=10.568,P=0.000.Granulocyte and macrophage colony forming unit count:(10.60±2.16)vs(5.55±1.54),t=8.512,P=0.000.The results of real time fluorescence quantitative PCR:the relative expression of PI3K was higher than that before operation.The relative expression of PI3K after operation was2.19±0.51 times compared with preoperative,t=10.365,P=0.000.AKT relative expression was higher than that of preoperative,and the relative expression of AKT was 2.27±0.59 times compared with preoperative,t=9.840,P=0.000.ConclusionsTransverse tibial bone transport therapy is a new effective treatment for diabetic foot.The possible mechanisms of treatment include two points:firstly,it can mobilize bone marrow stem cells(hematopoietic stem cells,mesenchymal stem cells,endothelial progenitor cells,etc.)to promote their proliferation,survival and migration to the site of diabetic foot ulcers for repair.Secondly,it can activate the SDF-1/CXCR4 axis and PI3K/AKT signaling pathway which involved in regulating the migration,differentiation and survival of bone marrow stem cells and promoting the healing of diabetic foot ulcers.
Keywords/Search Tags:transverse tibial bone transport, diabetic foot, hematopoietic stem cell, colony forming, PI3K/AKT signal pathway
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