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Effect Of Oscillatory Flow On Endothelial Cells In Arteriovenous Fistula

Posted on:2018-05-14Degree:MasterType:Thesis
Country:ChinaCandidate:J YangFull Text:PDF
GTID:2334330536986658Subject:Internal medicine Kidney disease
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Objective: Arteriovenous fistula is the lifeline of dialysis patients.The venous stenosis at the anastomotic site is the main cause of the dysfunction of the internal fistula.The pathological mechanism is intimal hyperplasia.Studies have shown that the turbulent shear force produced by the turbulence can promote the proliferation of endothelial cells.The inflammatory mediators in dialysis patients are closely related to oxidative stress,which can damage the vascular endothelial cells.Caveolin-1(caveolin-1,Cav-1)was found in vascular endothelial cells.It is a mechanical receptor located on the surface of vascular endothelium.It may be involved in the regulation of multiple signaling pathways in cells.The expression and distribution of cell surface proteins changed when the endothelial cells were subjected to shear stress.Transforming growth factor-β1(transforming growth factor-β1,TGF-β1)has the biological functions of inducing cell proliferation and migration,as well as promoting the accumulation of extracellular matrix.The aim of this study was to investigate the expression of Cav-1 and TGF-β1 1 in vascular endothelial cells under different modes of shear stress,in vitro.Methods: Application of in vitro oscillatory flow model to simulate the in vivo turbulent state,the peristaltic pump to control the flow rate,Injection pump manufacturing oscillatory flow,serum containing medium to simulate blood,umbilical vein endothelial cells simulating vein endothelial cells.The serum of uremic patients was added to the medium in proportion to simulate the uremic environment.Oscillatory flow effects of different time(0 hours,2 hours,6 hours and 12 hours)on endothelial cells were recorded.And below the physiological level of shear stress(6 dynes/cm2),physiological levels of shear stress(12 dynes/cm2)and super physiological shear stress(20 dynes/cm2)and the oscillatory shear stress(0±5 dynes/cm2)respectively for vein endothelial cells 12 h,the control group is not affected by the shear stress,and compare the effects of different shear stress on vascular endothelial cells.The expression levels of Cav-1 and TGF-β1 were detected by Western blotting and immunofluorescence technique at different shear stress and time.Results: The Cav-1 was gradually decreased with the extension of time,and the distribution was transferred from the plasma membrane to the cytoplasm.However,the expression level of TGF-β1 is on the contrary.Compared with the shear stress and the laminar shear stress of 12 h with different sizes,it is found that the expression of Cav-1 was decreased under oscillatory flow and low laminar shear stress.The expression of Cav-1 was increased at the physiological level and the control group.The expression of TGF-β1 was increased under oscillatory flow and low laminar shear stress.The expression was lower than that under physiological shear stress.In uremic environment,the activity of endothelial cells was lower than that of normal serum.The differences were statistically significant.Conclusion: Different forms of shear stress can affect the expression of cytokines.The changes of the structure and function of endothelial cells were caused by oscillatory shear stress,low shear stress and prolonged action time.It plays a key role in the failure of arteriovenous fistula.Uremic environment affects the expression of cytokines in vascular endothelial cells.
Keywords/Search Tags:Oscillatory flow, Disturbed wall shear stress, Hemodynamics, Arteriovenous fistula, endothelial cells, Uremia
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