罗格列酮降低氧化应激的作用:促进和动员内皮祖细胞参与了吗?  

Feasibility of rosiglitazone to improve mobilization of endothelial progenitor cells and reduce vascular oxidative stress in vivo

作　　者：赵清[1] 魏盟[1] 赵炳辉[2] 

机构地区：[1]上海交通大学附属第六人民医院心内科,上海市200233 [2]上海交通大学附属第六人民医院放射科,上海市200233

出　　处：《中国组织工程研究与临床康复》2010年第20期3650-3654,共5页Journal of Clinical Rehabilitative Tissue Engineering Research

基　　金：上海市科委项目资助(05JC14031)~~

摘　　要：背景:过氧化物酶增殖物激活受体γ激动剂可动员骨髓内内皮祖细胞至外周血中。然而,其动员内皮祖细胞的确切机制还不是很清楚。有实验证明,过氧化物酶增殖物激活受体γ受体激动剂可降低糖尿病小鼠的氧化应激反应。目的:明确过氧化物酶增殖物激活受体γ激动剂罗格列酮在体内是否通过降低氧化应激动员内皮祖细胞。方法:将24只雄性新西兰大白兔以数字表法随机分为3组:正常组、对照组和罗格列酮组,每组8只。对照组和罗格列酮组予高脂饮食2周后行颈动脉球囊损伤术,罗格列酮组术后第1天灌胃给予罗格列酮1mg/(kg?d),4周;对照组灌胃给予生理盐水。正常组仅切开颈部皮肤,给予正常饲料。术后4周以流式细胞仪测定CD34和KDR双阳性内皮祖细胞数量,Greiss法测定一氧化氮浓度,比色法检测超氧阴离子,RT-PCR法测量一氧化氮合酶及NADPH p22phox mRNA表达。结果与结论:24只兔均进入结果分析。与对照组比较,罗格列酮组兔内皮祖细胞数量、血清一氧化氮水平、清除超氧阴离子能力、一氧化氮合酶mRNA表达均明显升高(P<0.05),但仍低于正常组(P<0.05)。罗格列酮组兔NADPH p22phox mRNA表达明显低于对照组(P<0.05),与正常组接近(P>0.05)。3组血糖及血脂差异无显著性意义。在不依赖于降脂和降糖作用下,罗格列酮可能通过在转录水平降低NADPH氧化酶和增加一氧化氮合酶表达,从而降低氧化应激在体内动员内皮祖细胞。BACKGROUND： The peroxisome proliferator-activated receptor γ （PPAR-γ） agonists are found to have the ability to mobilize the endothelial progenitor cells （EPCs） from bone marrow to the peripheral circulation. However, the exact mechanism of its mobilization is not determined. It was found that PPAR-γ agonists have the ability to reduce the oxidative stress in diabetic mice. OBJECTIVE： To investigate whether PPAR-γ agonists, i.e., rosiglitazone, can mobilize endothelial progenitor cells via reducing oxidative stress in vivo. MATERIALS： A total of 24 New Zealand white rabbits were randomly divided into normal group, control group, and rosiglitazone group, with 8 rabbits for each group. Control group and rosiglitazone group were fed with high cholesterol diet and underwent carotid injury; rosiglitazone group was intragastrically injected with rosiglitazone （1 mg/kg per day） at 1 day after operation, and the injection lasted for 4 weeks; normal group was fed saline and only underwent cut-off cervical skin. After 4 weeks of treatment, CD34＋KDR＋ cell number characterized as EPCs was measured by flow cytometry. Nitric oxide （NO） level and superoxide anion （O2.-） were evaluated by Greiss reaction and colorimetry. Endothelial cell nitric oxide synthase （eNOS） and NADPH oxidase subunit p22phox mRNA expression were determined by reverse transcription polymerase chain reaction （RT-PCR）. RESULTS AND CONCLUSION： A total of 24 rabbits were included in the final analysis. Compared with control group, number of EPCs, NO level, clearing ability of superoxide anion, and eNOS mRNA expression were significantly increased in the rosiglitazone group （P 0.05）, which were still lower than normal group （P 0.05）. NADPHp22phox mRNA expression in the rosiglitazone group was significantly lower than control group （P 0.05） but closed to normal group （P 0.05）. There was no significant difference in blood glucose and blood fat. Rosiglitazone could mobilize EPCs in vivo independently by

关 键 词：罗格列酮 内皮祖细胞 一氧化氮合酶 NADPH氧化酶 超氧阴离子 

分 类 号：R318[医药卫生—生物医学工程]