| Hemodialysis is an important therapy for patients with end-stage renal disease, and arteriovenous fistula is the preferred vascular access in maintenance hemodialysis patients. A long-term stable vascular access are very important for The quality of life and survival time of patients with maintenance hemodialysis. From the establishment of arteriovenous fistula to have adequate blood flow used for dialysis, it need a period of time called mature period. In the process of internal fistula maturation, great changes have occurred in the blood flow dynamics of the artery and vein, and a series of pathological and physiological changes have been produced. Flow shear stress is an important factor affecting the maturation of internal fistula.PartⅠ Objective: Arteriovenous internal fistula is a non physiological product, created for hemodialysis. After the internal fistula was established, the arterial blood was mixed with venous blood flowing through the venous side to return to the heart. Because of the different of angles the blood vessel, diameter, the blood flow in the arteriovenous fistula is complex, which is often difficult to analyze and study. In this study, parallel plate flow chamber was used to simulate the lumen and blood flow. The CFD software was used to analyze the fluid type, the size and the distribution of the shear force in the parallel plate flow chamber. This is preparation of theory and practice for the analysis of complex blood flow of internal fistula. Methods: The parallel plate flow chamber was used to simulate the hemodynamic changes in the arteriovenous fistula. Using CFD software to model and analyze the distribution of fluid model and shear force in the interior of the flow chamber. results:(1) The system is drivied by pressure and pressure distribution of flow field has no big difference in X and Z direction. the pressure decreases gradually along the flow direction.(2) The whole computational domain for laminar flow, speed in a circular tube inlet after a formation parabolic distribution, and in narrow rectangular object block, fluid mixed with mixing, turbulent flow and vortex, into the bottom surface flow chamber(bottom) after fluid for stable and uniform flow. There is almost no change in velocity along the Y and X direction, but in the Z direction presented parabola distribution(typical Poiseuille flow characteristics). The biggest speed is at the middle.(3) The wall shear stress is larger at the bottom central laminar flow area are uniformly distributed. The near wall region due to the existence of vortex and vertical velocity gradient is small, so the area of wall shear stress is smaller. Between the two regions there is a region due to the existence of large velocity gradient, wall shear stress reaches the peak, but the area is very small. The effect of endothelial cell culture is relatively small.(4) The velocity gradient and the wall shear stress in the flow chamber were positively proportional to the wall shear stress. Conclusion:(1) The chamber is driven by fluid pressure and the pressure distribution decreases along the flow direction.(2) When the flow come into the bottom cavity, it become stable and uniform, and the velocity along the X and Y direction almost no change.(3) The greater the entrance flow, the larger flow and the greater wall shear stress. The shear stress and the velocity gradient is proportional to the fluid velocity in this study because of small shear force and speed changes is quite small.PartⅡ Objective: The endothelial cells, which are attached to the inner surface of the blood vessel, are the main subjects of various dynamic changes. Caveolin is distributed in the membrane of the endothelial cell surface, and is the receptors of shear stress acting on endothelial cells. This acting causing membrane surface protein expression and distribution changes. Under physiological conditions, flow shear force directly acts on vascular endothelial cells, mechanical receptors in endothelial cell surface after accepting stimulus, convert mechanical signals to biological signal which is transmitted to the nucleus. This affecting the biological function of endothelial cells. In this study, the changes of vascular endothelial cell function were studied at different time and different shear stress. So as to reveal the effect of blood flow on the function of vascular endothelial cells in arteriovenous fistula. Methods: Parallel plate flow chamber was used to simulate the venous lumen of the arteriovenous fistula. The medium was used to simulate the shear stress of blood flow, and the umbilical vein endothelial cells were used to simulate the vascular endothelial cells. Three kinds of forces was involved, stress lower than the normal level of shear stress, the physiological level of stress and the stress higher than physiologyical level. Shear stress action time was 0 hours, 6 hours, 12 hours and 24 hours. The expression of Cav-1, p-ERK, t-ERK, NF- and B were detected by blotting RT-PCR and Western in different shear stress and time. Results: Under physiological shear stress, the expression of Cav-1 in endothelial cells decreased with time, and the level of cytokine NF-κ B and p-ERK increased with time. Under the different shear stress for 12 hours, the endothelial cell expression of Cav-1 levels significantly increased with the enhancement of force and cytokine expression of NF-κ B and p-ERK expression in less than the role of physiological stress significantly more and with statistical significance, other shear expression differences had no statistical significance. Conclusion: the effect of shear stress on the expression of Cav-1 was significantly influenced by the time of action and the intensity of the shear stress. The expression of cytokine NF-κ B and p-ERK was time-dependent, and the effect of the low shear stress on the expression is larger. Therefore low shear and long-term effect influence on the function of endothelial cells larger, may be associated with fistula vascular intimal hyperplasia and thrombosis formation and local smooth muscle cell migrationPartⅢ Objective: Patients with end-stage renal disease began to appear high serum creatinine, calcium and phosphorus metabolism and metabolic acidosis and other complications in the late CKD. These factors will affect the function of vascular endothelial cells, resulting in endothelial cell injury. So the study of uremic environment, have important influence on endothelial cells of blood flow shear stress. Methods: Uremia environment is simulated by added certain concentration of uremic serum in culture medium. Shear stress below physiological level, shear stress of physiological level and stress beyond the physiological level is add on vascular endothelial cells. Shear stress action time was 0 hours, 6 hours, 12 hours and 24 hours. The expression levels of Cav-1, p-ERK, t-ERK, NF- and B were detected by blotting RT-PCR and Western in different shear stress and time. Results: Under the action of physiological shear stress, the expression of Cav-1 in endothelial cells decreased gradually with time, but the overall level of expression was lower. The level of cytokine NF-κ B and p-ERK increased with time, but the growth rate slowed down after 12 hours.Under the different shear stress for 12 hours, the endothelial cell expression of Cav-1 levels significantly increased with the enhancement of force and cytokine expression of NF-κ B and p-ERK expression in less than the role of physiological stress significantly more and with statistical significance, other shear expression differences had no statistical significance. Conclusion: In the uremic environment, the effect of strength and time both has influence on Cav-1 expression. The longer the time, the more the expression of cytokines of NF-κ B, p-ERK. Low shear force has larger effects on expression of NF-κ B, p-ERK. Therefore, in the uremic environment, low shear shear and long-term effect is effective stimulate on endothelial cell activation, which is associated with fistula vascular intimal hyperplasia, thrombus formation and the local smooth muscle cell migration. |
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