无症状高尿酸血症对原发性慢性肾小球肾炎血管内皮细胞及平滑肌细胞功能影响研究  

Effects of asymptomatic hyperuricemia on vascular endothelial cells and vascularsmoothmuscle cells in patients with primary chronic glomerulone-phritis

作　　者：连希艳[1] 黄胜华[1] 赵劲涛[1] 廖云娟[1] 李江[1] 袁志伟[1] 张瑜[1] 

机构地区：[1]昆明医科大学第二附属医院肾脏内科,昆明650101

出　　处：《中国实用内科杂志》2012年第10期791-795,I0001,共6页Chinese Journal of Practical Internal Medicine

基　　金：云南省科技厅资助项目(2009CD173)

摘　　要：目的通过观察无症状高尿酸血症对原发性慢性肾小球肾炎患者血管内皮细胞功能及平滑肌细胞增殖的影响,探讨无症状高尿酸血症是否能导致肾脏损害。方法将2009年6月至2011年6月昆明医科大学第二附属医院肾内科原发性慢性肾小球肾炎32例患者分为正常尿酸组与无症状高尿酸血症组。通过肾脏组织病理观察两组患者肾小血管的病变情况;用ELISA方法检测两组患者血浆中内皮细胞功能受损指标[一氧化氮(NO)、内皮素-1(ET-1)、纤溶酶原激活物抑制剂-1(PAI-1)],血管平滑肌增殖指标[血小板衍生因子(PDGF)、环氧化酶(COX2)、中性粒细胞趋化因子-1(MCP-1)]以及炎性反应指标[白介素-18(IL-18)、肿瘤坏死因子-α(TNF-α)];免疫组化法检测各组肾脏组织中PDGF、一氧化氮合酶(NOS)的表达;并分别对内皮细胞功能及平滑肌细胞增殖的影响因素进行多因素回归分析。结果无症状高尿酸血症组与正常尿酸组相比,NO浓度明显降低(P<0.05);ET-1、PAI-1、PDGF、COX2、IL-18、TNF-α、MCP-1浓度明显升高(P<0.05);经别嘌呤醇干预后上述指标均明显改善(P<0.05)。肾组织病理:光镜下可见无症状高尿酸血症组肾小血管明显病变;免疫组化无症状高尿酸血症组NOS的表达明显减少,PDGF的表达明显增加。经多因素回归分析,无症状高尿酸血症为内皮细胞功能损伤及血管平滑肌细胞增殖的独立影响因素。结论无症状高尿酸血症可导致肾小球内皮细胞功能受损及血管平滑肌细胞增殖。Objective To explore the effects of asymptomatic hyperuricemia on the function of glomerular endothelial cells and vascular smooth muscle cell proliferation in patients with primary chronic glomerulonephritis and to determine if asymptomatic hyperuricemia could lead to kidney injury. Methods Patients with primary chronic glomerulonephritis enrolled in the study were assigned to normouricemia group and hyperuricemia group, respectively. The pathological variation in small vessels was determined via histopathological examination. Plasma indices reflecting endothelial dysfunction, including nitric oxide （NO）,endothelin-1 （ET-1） and plasminogen activation inhibitor-1 （PAI-1） were detected by using enzyme-linked immunosorbent assay （ELISA）. ELISA was also employed to assess the levels of markers representing vascular smooth muscle cell proliferation, including platelet-derived growth factor （PDGF）, cyclooxygenase-2 （COX-2） and macrophage chemotatic protein-1 （MCP-1） as well as inflammatory markers,for instance,interleukin-18 （IL-18） and tumor necrosis factor-α （TNF-α）. The levels of PDGF and nitric oxide synthase （NOS） in the kidneys were measured via immunohistochemical assay. Multivariate Logistic regression analysis was applied to investigate the factors contributing to endothelial cell dysfunction and smooth muscle cell proliferation. Results Asymptomatic hyperuricemia group yielded significantly lower concentration of NO and markedly higher concentration of COX2,ET-1, IL-18, PAI-1 ,PDGF,TNF-α and MCP-1 as compared with nor- mouricemia group （ all P 〈 0. 05 ）. Treatment of allopurinol has resulted in dramatic improvement in all aforementioned indi-ces （ all P 〈 0. 05 ）. Patients with asymptomatic hyperuricemia showed overt glomerular vascular variation under light mi- croscopy and significantly reduced NOS expression yet markedly increased PDGF expression as assessed by immunohisto- chemistry＋ assay. Multivariate Logistic regression analysis showed that asym

关 键 词：无症状高尿酸血症 肾小球内皮细胞 血管平滑肌细胞 肾小球疾病 

分 类 号：R589.7[医药卫生—内分泌]