糖尿病大鼠肾小球VEGF-NO轴失衡在2型糖尿病早期肾病发生中的作用  

Uncoupling of VEGF-NO axis related to endothelial dysfunction in early diabetic nephropathy

作　　者：黄娜[1] 赵建刚[1] 侯宁宁[1] 韩芳[2] 刘雪[1] 孙晓东[1] 

机构地区：[1]潍坊医学院附属医院(临床学院)内分泌科,山东省261031 [2]潍坊医学院附属医院(临床学院)病理科,山东省261031

出　　处：《中华临床医师杂志（电子版）》2014年第4期64-67,共4页Chinese Journal of Clinicians(Electronic Edition)

基　　金：国家自然科学基金(81300688)

摘　　要：目的探讨2型糖尿病早期肾病肾小球血管内皮生长因子-一氧化氮(VEGF-NO)轴失衡,血管内皮细胞功能障碍在2型糖尿病早期肾病发生中的作用。方法将20只Wistar雄性大鼠随机分为正常对照组(NC组)和糖尿病肾病组(DN组)。NC组予普通饲料喂养,DN组予高糖高脂饲料喂养并腹腔注射小剂量链脲佐菌素(30 mg/kg)建立2型糖尿病肾病早期大鼠模型。造模成功后检测大鼠血糖(GLU)、血胰岛素(INS)、胆固醇(CHO)、甘油三酯(TG)、丙二醛(MDA)、超敏C反应蛋白(hs-CRP)浓度,尿白蛋白/肌酐(ACR)比值,取胸主动脉于器官浴槽中观察离体胸主动脉对乙酰胆碱或硝普钠的舒张反应。用免疫组化法检测肾小球CD34、VEGF表达水平,Griess法检测肾小球NO浓度。结果与NC组比较,DN组GLU、INS、CHO、TG、MDA、hs-CRP、ACR水平明显升高(P<0.01)。DN组大鼠内皮依赖性血管舒张功能明显受损。与NC组比较,DN组大鼠肾小球CD34表达明显增多(P<0.05),VEGF蛋白表达明显升高(P<0.05),NO水平明显减少(P<0.05)。结论肾小球VEGF-NO轴失衡与糖脂代谢紊乱所致的炎症和氧化应激增多有关,VEGF-NO轴失衡引起内皮细胞功能紊乱,导致2型糖尿病肾病早期尿微量白蛋白排出量增多。Objective To investigate the effect of endothelial dysfunction induced by uncoupling of vascular endothelial growth factor-nitric oxide（VEGF-NO） axis on microalbuminuria in early diabetic nephropathy. Methods Twenty male Wistar rats were randomly divided into 2 groups： the normal rats（NC group） fed with normal diet, and the early stage of type 2 diabetic nephropathy rats（DN group） established by sucrose and fat-enriched diet and intraperitoneal administration of low-dose streptozotocin（STZ, 30 mg/kg）. After the early type 2 diabetic nephropathy models were established, rats were sacrificed, and blood glucose（GLU）, insulin（INS）, cholesterol（CHO）, triglyceride（TG）, high-sensitivity C-reactive protein（hs-CRP） and malonic dialdehyde（MDA） in serum were measured, urinary albumin/creatinine ratio（ACR） was tested, and pathological change in kidney was examined by microscopy. The thoracic aortas rings were harvested and equilibrated in Krebs-Henseleit solution to measure the endothelial dependent/independent vasodilation in response to Acetylcholine/Sodium nitroprusside. Kidney tissues were collected for CD34 and VEGF immunohistochemistry. Glomerular NO were measured by Griess reaction. Results GLU, INS, CHO, TG, hs-CRP and MDA were significantly increased in DN group than NC group（P0.01）. Compared to the NC group, endothelial dependent vasodilation was obviously impaired（P0.01）. CD34 expression in glomeruli was significantly increased in DN group as compared toNC group（P0.05）. VEGF expression was increased and NO levels were reduced in DN group compared with NC group（P 0.05）. Conclusion The uncoupling of VEGF-NO axis which was caused by inflammation and oxidative stress in diabetic mellitus, induced endothelium dysfunction and was responsible for the microalbuminuria in early type 2 diabetic nephropathy.

关 键 词：糖尿病肾病 内皮生长因子 一氧化氮 内皮细胞功能障碍 

分 类 号：R587.2[医药卫生—内分泌] R692[医药卫生—内科学]