| Background and purposeArteriovenous fistula(AVF)is the primary hemodialysis vascular access for patients with chronic kidney disease,and its infection rate,thrombosis rate and health care costs are lower than other types of hemodialysis access.After AVF angioplasty,anastomotic vein is in an arterial environment of high pressure and high blood flow.In the process of adaptive remodeling of anastomotic veins,excessive venous hyperplasia and lumen stenosis are caused by hemodynamic factors or other biological factors,and finally AVF fails to mature.This greatly increases the re-hospitalization rate and mortality rate of uremia patients,bringing heavy burden to the social economy.Therefore,exploring the pathophysiological mechanism,prevention and treatment of AVF intima hyperplasia is an important issue that needs to be solved clinically.In this study,the expression of Eph-B4-Cav-1 axis and MMP-9 in AVF intima hyperplasia in uremia patients were investigated by observing the pathological and morphological changes of venous vascular tissues,and the influence of the above proteins on the maturation process of AVF was studied.MethodsAmong the maintenance hemodialysis patients in our hospital,20 patients who underwent AVF angioplasty were selected as the AVF plasty group,and the normal vein tissue was discarded when ligating the vein.Patients with AVF reconstruction caused by AVF stenosis were selected as AVF hypertrophic vein group.According to the use time of internal fistula,AVF hypertrophic vein group was divided into three subgroups:0-6 months group,6-12 months group and>12 months group.10 cases of abandoned hypertrophic vein tissue near fistula were collected in each subgroup,and30 cases were collected in AVF hypertrophic vein group.Clinical information of enrolled patients was collected,the histomorphological changes of vascular tissue were observed after HE staining,Masson staining and reticular fiber staining,and the intima and media thickness of vascular tissue were measured and compared.The expression levels of Eph-B4,Cav-1,MMP-9 andα-SMA in venous tissues were detected by immunohistochemical staining.Apply Image J software to analyze and process images,IBM SPSS 25.0 statistical software to analyze data.Results1.The level of C-reactive protein in hypertrophic vein group was higher than that in AVF angioplasty group(9.64mg/L±6.23mg/L,13.65mg/L±5.48mg/L,P<0.05).There was no significant difference in WBC level(6.25×10~9/L±1.21×10~9/L,6.32×10~9/L±1.22×10~9/L,P>0.05).2.Compared with AVF angioplasty group,the intima and media thickness of hypertrophic vein in AVF group were increased,and intima thickening was the main one.The average intimal thickness(27.56μm±5.31μm,186.56μm±79.22μm,P<0.001),average media thickness(83.46μm±24.15μm,129.43μm±38.93μm,P<0.001),average intima/media ratio(0.35±0.08,1.47±0.54,P<0.001).There was significant difference in mean intimal thickness and mean intima/media ratio among the three subgroups of AVF hypertrophic vein group(P<0.001),but there was no significant difference in average media thickness(P>0.05).3.There was a significant difference in venous vascular structure between the two groups after HE staining.In the AVF angioplasty group,there were clear layers and boundaries of intima,media and adventitia.In the AVF hypertrophic vein group,the boundary between the endometrium and the endometrium was blurred,and there were a large number of irregular smooth muscle cells in the endometrium,and the number of cells in the endometrium and the middle membrane was significantly increased.A large number of chronic inflammatory cells were found in the endometrium,and the extracellular matrix showed myxoid degeneration.4.The results of Masson staining and reticular fiber staining showed that there were a large number of disordered collagen fibers and reticular fibers in the thickened intima of the veins in the two groups.There was a significant difference in the volume fraction of venous collagen between the two groups(32.92%±3.64%,50.61%±5.79%,P<0.001).5.Immunohistochemical staining results showed that the number and staining intensity of Eph-B4 and Cav-1 protein in endothelial cells of AVF hypertrophic vein group were significantly lower than that of AVF angioplasty group.In each subgroup of AVF hypertrophic vein,when the use time of internal fistula was gradually prolonged,the intima thickness also gradually increased,while the expressions of Eph-B4 and Cav-1 gradually decreased,and the hyperplasia degree was serious,even the expressions of Eph-B4 and Cav-1 were lower in almost occluded venous endothelium,and the expression of MMP-9 was significantly increased in the thickened vein tissue.The number of MMP-9 positive cells in AVF hypertrophic vein group were 30.0(4.07)cell/10~4μm~2,and that in AVF angioplasty group were12.5(7.67)cell/10~4μm~2.There was statistical difference in MMP-9 expression between the two groups(P<0.001).The expression ofα-SMA in thickened vein tissue was significantly increased.The number ofα-SMA positive cells in AVF angioplasty group and AVF hypertrophic vein group were(3.39±1.24)cell/10~4μm~2and(30.37±6.83)cell/10~4μm~2,respectively.There was statistical difference in the expression ofα-SMA between the two groups(P<0.001).Conclusions1.The hyperplasia of AVF veins is mainly characterized by intima thickening,and the migration and proliferation of vascula smooth muscle cells are involved in this process.2.It was preliminarily confirmed in clinical trials that decreased expression of EPH-B4-CAV-1 axis and increased expression of MMP-9 could promote hyperplasia of AVF intima... |
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