维持性血液透析患者自体动静脉内瘘血管内膜增生的机制研究  

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

作　　者：李泽争 王葳[1] 陆石[1] 于秀峙[1] 王巍巍[1] 张金元[1] 

机构地区：[1]解放军第四五五医院肾脏科南京军区肾脏病研究所,上海200052 [2]上海中医药大学,上海201203

出　　处：《中国血液净化》2016年第6期330-334,共5页Chinese Journal of Blood Purification

基　　金：南京军区医学科技创新项目(No.12MA017)

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（AVF）血管内膜增生的影响及可能作用机制。方法 收集维持性血透患者行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，HE染色观察血管组织形态学变化，并测量各组血管组织的内膜、中膜厚度；免疫组织化学法检测血管平滑肌肌动蛋白（a-SMA）的表达。选取对照组（AVF 0月时的血管组织）和内瘘使用寿命在12-18月的血管组织，免疫组化检测碱性成纤维细胞生长因子（bFGF）、胰岛素生长因子1（IGF-1）、血管内皮生长因子（VEGF）、金属基质蛋白酶2（MMP2）及金属基质蛋白酶9（MMP9）的表达变化，并分析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（hasic 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 growthfactor，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�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 ofAVF 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. Histologi- cal changes were examined and the thickness of intima and media was measured after H-E staining of the sampie. lmmunohistochemistry was used to detect the expression of several growth factors in vascular tissue. The correlation between cc-SMA and growth factors was then analyzed. Results lntima thickness increased more in hypertensive nephropathy and diabetic nephropathy groups than in chronic glomerulonephritis group. Immunohistochemical staining showed that α-SMA, bFGF, IGF-I and MMP-9 increased significantly after the surgery for 12-18 months in hypertensive nephropathy and diabetic nephropathy groups. In contrast, VEGF re- duced significantly, and MMP-2 had no changes. Univariate regression analysis revealed that ct-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 diabe- tes can accelerate the processes of intima hyperplasia and shorten the life of fistula, especially in MHD pa- tients with diabetes.

关 键 词：血管通路 自体动静脉内瘘 内膜增生 高血压 糖尿病 

分 类 号：R318.16[医药卫生—生物医学工程]