Study On The Mechanism Of Cell Proliferation And Apoptosis In Autologous Arteriovenous Fistula

Objective: Hemodialysis is an indispensable treatment for patients with end-stage renal disease.Good function of vascular access is an important guarantee for adequate dialysis.Autogenous Arteriovenous Fistula(AVF)is the preferred vascular access for hemodialysis in patients with end-stage renal disease.However,one year patency rate of AVF is usually only in the range of 60-65%.Stenosis is known to be the most common complication of AVF.Studies have found that the incidence of stenosis is as high as 90% in AVF complications,and that the incidence of proximal anastomotic stenosis,reaching 71%,is the highest.Stenosis of AVF is mainly caused by intimal hyperplasia.In terms of the mechanism of intimal hyperplasia,the currently accepted theory is the proliferation and migration of vascular smooth muscle cells(VSMCs),inflammatory cell infiltration,extracellular matrix deposition and neovascularization in the adventitia and intima.Yukihiro Hayakawa et al.showed that there is an imbalance between cell proliferation and apoptosis in AVF brachial artery intimal hyperplasia,while little is known about apoptosis in AVF venous intimal hyperplasia.The purpose of this study was to further investigate the relationship between cell proliferation and apoptosis and the mechanism of AVF stenosis by detecting the expression of PCNA,bcl-2 and bax that are related to apoptosis and proliferation of autologous arteriovenous stenosis to provide theoretical evidence for the prevention and treatment of AVF stenosis.Method: Abandoned venous vascular tissues were collected during the surgery of AVF angioplasty or reconstruction for the end-stage renal disease patients in the Third Hospital of Hebei Medical University from November 2016 to November 2017.The stenosis and non-stenotic vascular tissues of patients who underwent AVF reconstruction were set as experimental group A(n=10)and experimental group B(n=10)respectively.The distal vascular tissue of the vein to be ligated during the first AVF angioplasty was set as the control group(n=10).Morphological changes of vascular tissue were observed by hematoxylin-eosin staining(HE)method.The expressions of PCNA,bcl-2 and bax in the vascular wall of each group were detected by immunohistochemical staining.The experimental data was analyzed by SPSS 21.0 statistical software.The results were expressed by mean +standard deviation(x+s).“P<0.05” indicated that there was significant difference.Results: There was no significant difference in age and sex among groups(P > 0.05).1.HE staining.The intima and tunicae media of the experimental group A and the experimental group B were observed to be thickened to different extent.Thickening of the intima is more pronounced than that of the tunicae media,and thickening of the intima was more obvious in experimental group A than in experimental group B.Moreover,the intima of the experimental group A was unevenly thickened,some convexing toward the lumen which was narrowed.In the experimental group B,the degree of intimal thickening was relatively small,no obvious protruding to lumen which was not narrow was observed.There was no obvious thickening of the intima of the control group.2.immunohistochemical staining.Image profession plus 6.0 image analysis software was used to analyze image optical density.Expression of PCNA was showed so strong positive that the difference was significant(P<0.01)in experimental group A(58.37 ± 20.76),compared with experimental group B(32.78±8.65)and control group(10.94±2.30);when we compared the expression of PCNA between experimental group B and the control group,the difference was also significant(P<0.01).Expression of Bcl-2 was strongly positive in experimental group A(64.52±21.16),compared with experimental group B(42.83±10.84)and control group(11.09±2.91),so that the difference was significant(P<0.01);when we compared the expression of Bcl-2 between experimental group B and the control group,the difference was also significant(P<0.01).Expression of Bax was positive in the experimental group,but there was no significant difference between the experimental group A(43.70±14.31)and the experimental group B(44.02±9.58)(P>0.05).Bax was weakly positively expressed in the control group(10.06±2.20),and the difference between the experimental group and the control group was significant(P<0.01).The difference of Bax/bcl-2 ratio between experimental group A(0.71 ± 0.21)and experimental group B(1.09±0.36)was significant(P<0.05).Conclusions:AVF stenosis is the main cause of AVF failure after maturation.Both cell proliferation and apoptosis are involved in the development of endogenous proliferation.The establishment of AVF results in that cell proliferation and apoptosis are increased,that intima is thickened,that blood vessel is benignly remodeled,and that Internal fistula maturation could be used for hemodialysis.When cell proliferation is further increased while apoptosis is relatively reduced,the intima is excessively thickened,and the blood vessels are malignantly remodeled,leading to stenosis in turn.