罗格列酮改善晚期糖基化终产物导致的皮祖细胞功能损伤  

Rosiglitazone ameliorates the dysfunction of endothelial progenitor cells induced by advanced glycation end products

作　　者：谭鸿斌[1] 姜其钧[1] 吴建详[1] 梁春[1] 刘星[1] 任雨笙[1] 吴宗贵[1] 

机构地区：[1]第二军医大学附属长征医院心内科,上海200003

出　　处：《上海医学》2009年第4期283-288,共6页Shanghai Medical Journal

基　　金：国家重点基础研究发展计划(973计划)资助项目(2005CB523309)

摘　　要：目的探讨过氧化物酶体增殖物激活受体γ(PPARγ)激动剂能否改善由于晚期糖基化终产物(AGEs)导致的内皮祖细胞(EPCs)功能损伤。方法将培养的健康成人外周血EPCs置于含有不同质量浓度的糖基化人血清白蛋白(AGE-HSA)的培养基中培养,分别为人血清白蛋白(HSA,对照组),AGE-HSA50mg/L(AGE-HSA50mg/L组)、AGE-HSA100mg/L(AGE-HSA100mg/L组),AGE-HSA200mg/L(AGE-HSA200mg/L组),AGE-HSA200mg/L+罗格列酮10nmol/L(AGE-HSA+罗格列酮组),AGE-HSA200mg/L+抗AGEs受体(RAGE)抗体50mg/L(AGE-HSA+RAGE组)。另设立一个空白对照组。检测EPCs的增殖、黏附、迁移、NO分泌能力、凋亡和血管细胞黏附分子-1(VCAM-1)的分泌情况。结果AGE-HSA200mg/L组的EPCs增殖率较空白对照组显著下降(37.7±6.3)%(P<0.05),显著低于AGE-HSA+罗格列酮组的(89.3±5.9)%(P<0.05)。AGE-HSA200mg/L的黏附细胞数、迁移细胞数分别为(20.2±1.3)、(15.0±2.1)个/高倍视野,均显著低于空白对照组的(35.6±1.5)、(28.6±2.8)个/高倍视野(P值均<0.05)。AGE-HSA200mg/L组的凋亡率为(15.2±1.0)%,显著高于空白对照组的(4.6±0.8)%(P<0.05)。AGE-HSA+罗格列酮组的黏附细胞数为(31.2±2.6)个/高倍视野,迁移细胞数为(21.6±3.1)个/高倍视野,凋亡率为(6.1±0.9)%,与AGE-HSA200mg/L组的差异均有统计学意义(P值均<0.05)。AGE-HSA+罗格列酮组的EPCs培养上清液中的NO含量为(16.2±1.0)μmol/L,显著高于AGE-HSA200mg/L组的(10.2±0.5)μmol/L(P<0.05),VCAM-1为(5.2±0.04)μg/L,显著低于AGE-HSA200mg/L组的(6.2±0.1)μg/L(P<0.05)。结论PPARγ激动剂罗格列酮能够改善AGEs导致的EPCs功能损伤。Objective To investigate whether peroxisome proliferator-activated receptor-gamma （PPARγ） agonists rosiglitazone can ameliorate the dysfunction of endothelial progenitor cells （EPCs） induced by advanced glycation end products （AGEs）. Methods EPCs isolated from healthy adults were cultured with various concentrations of advanced glycation end product-human serum albumin （AGE-HSA） （0, 50, 100 and 200 mg/L） for 24 h in the absence or presence of rosiglitazone （10 nmol/L）, anti-RAGE antibody （50 mg/L）. We also included a blank control group, The proliferation, apoptosis, cell adhesion, migration, NO production and vascular cell adhesion molecule （VCAM）-1 secretion by EPCs were assessed. Results AGE-HSA at 200 mg/L significantly impaired the proliferation （reduced by [37.7 ±6.3]% compared with control, P〈0. 05）, adherent （[35.6±1.5]/HPF vs. [20.2± 1.3]/HPF, P〈0.05）, and migration （[28.6±2.8]/HPF vs. [15.0±2. 1]/HPF, P〈0.05） of EPCs, and aggravated the apoptosis （[4.6 ±0.8]% vs. [15.2 ± 1.0]%, P〈0.05） of EPCs. Rosiglitazone significantly reversed the impairment effect of AGE-HSA on the proliferation （increased to [89.3 ±5.9]%, P〈0.05）, adherent （ increased to[31.2 ± 2.6]/HPF, P〈0.05） and migration （increased to [21.6 ± 3.1]/HPF, P 〈0.05） of EPCs, and ameliorated the apoptosis （reduced to [6. 1 ±0.9] %, P〈0.05） of EPCs. Rosiglitazone also increased the production of NO （[16.2 - 1. 0]μmol/L vs. [10.2 -0.51]μmol/L, P〈0,05） and reduced the secretion of VCAM-1 （[5.2±0.041μg/L vs. F6.2±0.11μg/L,P〈0.05） of EPCs. Conclusion PPARy agonist rosiglitazone ameliorates the dysfunction of endothelial progenitor cells induced by advanced glycation end products.

关 键 词：内皮祖细胞 晚期糖基化终产物 晚期糖基化终产物受体 凋亡 迁移 过氧化物酶体增殖物激活受体Γ激动剂 

分 类 号：R587.2[医药卫生—内分泌]