中国血液净化

中国血液净化 ›› 2016, Vol. 15 ›› Issue (06): 330-334.doi: 10.3969/j.issn.1671-4091.2016.06.004

• 血管通路 • 上一篇    下一篇

维持性血透患者自体动静脉内瘘血管内膜增生的机制研究

李泽争1.2 ,王葳1, 陆石1 ,于秀峙1 ,王巍巍1 ,张金元1   

  1. 1. 解放军第四五五医院肾脏科  2. 上海中医药大学
  • 收稿日期:2015-10-30 修回日期:2016-04-12 出版日期:2016-06-12 发布日期:2016-06-19
  • 通讯作者: 王巍巍 w.vwei@163.com E-mail:985704026@qq.com
  • 基金资助:

    南京军区医学科技创新项目(No.12MA017)

The mechanism of neointimal hyperplasia in autologous internal arteriovenous fistula in maintenance hemodialysis patients

  • Received:2015-10-30 Revised:2016-04-12 Online:2016-06-12 Published:2016-06-19

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摘要： 目的探讨高血压肾损害及糖尿病肾病对维持性血液透析患者自体动静脉内瘘(arteriovenous fistula，AVF)血管内膜增生的影响及可能作用机制。方法收集维持性血液透析患者行AVF 成形术及重建术时的头静脉血管组织，将其按原发病的不同分为慢性肾小球肾炎组、高血压肾损害组及糖尿病肾病组，苏木素-伊红染色观察血管组织形态学变化，测量各组内膜、中膜厚度；免疫组织化学法检测各生长因子的表达变化，并分析血管平滑肌肌动蛋白(vascular smooth muscle actin，a-SMA)与各生长因子之间的相关性。结果在12～18 月与慢性肾小球肾炎组相比，高血压肾损害组(t=4.366，P=0.001)与糖尿病肾病组(t=13.451，P＜0.001)内膜厚度均明显增加；免疫组化染色显示在12～18 月，与慢性肾小球肾炎组比较，高血压肾损害组和糖尿病肾病组碱性成纤维细胞生长因子(basic fibroblast growth factor，bFGF)、胰岛素生长因子1(insulin-like growth factor 1，IGF-1)、金属基质蛋白酶9 (matrix metalloproteinase9，MMP9)的表达水平随内膜厚度的增加而明显上调(bFGF：41.67%±7.11%，54.33%±3.51%，63.33%±4.04%，F=24.570，P=0.038；IGF-1：26.67%±4.16%，38.67%±5.51%，48.00%±2.65%，F=17.051，P=0.043；MMP9：42.00%±2.65%,66.00%±4.03%,81.00%±3.61%，F=5.420，P=0.045),血管内皮生长因子(vascular endothelial growth factor，VEGF) 表达显著降低(48.00% ± 7.03% ，40.67%±3.05%，21.00%±2.02%,F=28.140,P＜0.001)，金属基质蛋白酶2(matrix metalloproteinase 2，MMP2)表达量无明显变化(9.67%±0.58%，10.33%±1.52%，12.67%±2.31%，F=0.903，P=0.415)。相关性分析发现a-SMA 表达水平与bFGF、IGF-1、MMP9 的表达存在明显正相关(r=0.586，P=0.000；r=0.606,P=0.000；r=0.722,P=0.000)，与VEGF 的表达呈负相关(r=-0.541，P=0.000)。结论AVF 内膜增生主要以血管平滑肌细胞(vascular smooth muscle cell,VSMC)增生为主，VSMC 的增殖可能与bFGF、IGF-1、MMP9的表达水平上调、VEGF 活性抑制有关；高血压、糖尿病可加速血管内膜增生进程，缩短内瘘使用寿命，且糖尿病促进内膜增生的作用更加显著。

关键词: 血管通路, 自体动静脉内瘘, 内膜增生, 高血压, 糖尿病

Abstract: Objective To evaluate the influence and mechanism of hypertensive nephropathy and diabetic nephropathy on neointimal hyperplasia in autologous internal arteriovenous fistula (AVF) in maintenance hemodialysis (MHD) patients. Methods Cephalic veins were collected during the surgery of AVF angioplasty or reconstruction for MHD patients. The samples were divided into chronic glomerulonephritis group, hypertensive nephropathy group and diabetic nephropathy group based on primary disease of the patients. Histological changes were examined and the thickness of intima and media was measured after H-E staining of the sample. Immunohistochemistry was used to detect the expression of several growth factors in vascular tissue. The correlation between α-SMA and growth factors was then analyzed. Results Intima thickness increased more in hypertensive nephropathy and diabetic nephropathy groups than in chronic glomerulonephritis group. Immunohistochemical staining showed that α-SMA, bFGF, IGF-1 and MMP-9 increased significantly after the surgery for 12-18 months in hypertensive nephropathy and diabetic nephropathy groups. In contrast, VEGF reduced significantly, and MMP-2 had no changes. Univariate regression analysis revealed that α-SMA level was positively correlated with the levels of bFGF, IGF-1 and MMP-9, and negatively correlated with the level of VEGF in vascular tissue. Conclusions Proliferation of vascular smooth muscle cells (VSMCs) was the leading cause of intima hyperplasia in MHD patients. The up- regulation of bFGF, IGF- 1 and MMP-9 and down-regulation of VEGF in vascular tissue may relate to the VSMCs proliferation. Hypertension and diabetes
can accelerate the processes of intima hyperplasia and shorten the life of fistula, especially in MHD patients with diabetes.

Key words: Vascular access, Autologous arteriovenous fistula, Intimal hyperplasia, Hypertension, Diabetes