中国全科医学2017，Vol.20Issue(16)：1961-1967,7.DOI:10.3969/j.issn.1007-9572.2017.16.012
不同尿白蛋白排泄率2型糖尿病患者血清HIF-1α、VEGF、vWf、IGF-1、25(OH)D3水平及其相互关系研究
Changes of Serum HIF-1α,VEGF,vWf,IGF-1,25(OH)D3 Levels and Their Correlation in Type 2 Diabetes Mellitus Patients with Different Urinary Albumin Excretion Rates
摘要
Abstract
Objective To investigate the changes of serum hypoxia-inducible factor-1 alpha(HIF-1α),vascular endothelial growth factor(VEGF),von Willebrand factor(vWf),insulin-like growth factor-1(IGF-1),25-hydroxyvitamin D3〔25(OH)D3〕 levels and their correlation in type 2 diabetes mellitus(T2DM) patients at different stages of diabetic nephropathy(DN) determined by urinary albumin.Methods Four hundred and twenty-three outpatients and inpatients with T2DM(case group) admitted to the First Hospital Affiliated to China Medical University between June 2012 and November 2014 were included in this study.They were compared with 165 gender-and age-and BMI-matched healthy adults(control group) undergoing physical examination in the same hospital during the same period.For further and detailed study,in accordance with the level of urinary albumin excretion rate〔which is expressed with albumin/creatinine ratio(ACR)〕,we divided the case group into normoalbuminuric subgroup(ACR<30 mg/g,n=163),microalbuminuric subgroup(ACR ranges 30~300 mg/g,n=145),and macroalbuminuric subgroup(ACR>300 mg/g,n=115).The levels of serum HIF-1α,VEGF,vWf,and IGF-1 were determined by enzyme-linked immunosorbent assay(ELISA),and 25(OH)D3 was measured by chemiluminescent immunoassay(CLIA) in all the subjects.Results Duration of T2DM,waist circumference,waist to hip ratio(WHR),fasting plasma glucose(FPG),glycosylated hemoglobin(HbA1c),total cholesterol(TC),triacylglycerol(TG),low-density lipoprotein cholesterol(LDL-C),serum creatinine(SCr),blood urea nitrogen(BUN),uric acid(UA),fibrinogen(Fg),fasting insulin(FINS),homeostasis model assessment-insulin resistance(HOMA-IR),Ln(ACR),HIF-1α,VEGF,vWf,IGF-1 and 25(OH)D3 differed significantly between the control group,and normoalbuminuric,microalbuminuric and macroalbuminuric subgroups(P<0.05),while gender,average age,BMI,and high-density lipoprotein cholesterol(HDL-C) did not(P>0.05).Pearson correlation analysis found that,HIF-1α had linear positive correlation with VEGF,vWf as well as IGF-1(P<0.05);VEGF was linearly and positively correlated with vWf along with IGF-1(P<0.05);linear positive correlation was found between vWf and IGF-1(P<0.05);while 25(OH)D3 showed linear negative correlation with HIF-1α,VEGF,vWf,and IGF-1(P<0.05).Results of Spearman′s rank correlation coefficient analysis demonstrated that,Ln(ACR)was positively associated with the duration of T2DM,waist circumference,WHR,HbA1c,TC,TG,LDL-C,SCr,BUN,UA,Fg,HOMA-IR,HIF-1α,VEGF,vWf and IGF-1(P<0.05),while it was negatively associated with 25(OH)D3(P<0.05).Multiple stepwise regression and principal component regression analysis revealed that the duration of T2DM,TG,LDL-C,SCr,BUN,UA,HOMA-IR,HIF-1α,VEGF,vWf,IGF-1,25(OH)D3 were the correlation factors for Ln(ACR)(P<0.05),with a regression equation of Y[Ln(ACR)]=2.553+0.967×principal component +0.024×duration of T2DM +0.123×TG+0.147×LDL-C+0.018×SCr+0.195×BUN+0.003×UA+0.033×HOMA-IR-0.045×25(OH)D3,principal component =0.827×HIF-1α+0.846×VEGF+0.727×vWf +0.931×IGF-1.Conclusion In T2DM patients,with the increase of Ln(ACR),the levels of serum HIF-1α,VEGF,vWf and IGF-1 were gradually increased,while serum 25(OH)D3 was gradually decreased.Serum levels of HIF-1α,VEGF,vWf,IGF-1 may be involved in the occurrence and progression of DN through chronic inflammation,promoting angiogenesis,endothelial injury and dysfunction.These pathogeneses interact with each other and promote each other;25(OH)D3 may have protective effect on DN,and its protective effect is realized at least in part by inhibiting the inflammatory reaction,abnormal angiogenesis and inhibiting vascular endothelial dysfunction.关键词
糖尿病肾病/低氧诱导因子-1α/血管内皮生长因子类/血管性血友病因子/胰岛素样生长因子Ⅰ/骨化二醇Key words
Diabetic nephropathy/Hypoxia-inducible factor Ⅰ alpha/Vascular endothelial growth factors/Von willebrand factor/Insulin-like growth factor Ⅰ/Calcifediol分类
医药卫生引用本文复制引用
邵滢,吕川,马小羽,王秋月..不同尿白蛋白排泄率2型糖尿病患者血清HIF-1α、VEGF、vWf、IGF-1、25(OH)D3水平及其相互关系研究[J].中国全科医学,2017,20(16):1961-1967,7.基金项目
辽宁省高等学校"高端人才队伍建设工程"项目(〔2014〕187) （〔2014〕187）
