吡格列酮对代谢综合征大鼠骨髓内皮祖细胞黏附能力的促进作用及其机制  

The peroxisome proliferator activated receptor 3＇ agonist pioglitazone can improve adhesion of endothelial progenitor cells from bone marrow in rat model of metaboic syndrome and its mechanism exploration

作　　者：刘洪智[1] 赵子牛[2] 程兆云[2] 范磊[3] 杨俊朋[4] 吕丽芳[4] 马跃华[4] 虎子颖[4] 徐予[4] 高传玉[4] 张会峰[4] 

机构地区：[1]郑州大学人民医院心内科,450003 [2]郑州大学人民医院心外科,450003 [3]郑州大学人民医院创伤外科,450003 [4]郑州大学人民医院内分泌科,450003

出　　处：《中华实验外科杂志》2017年第2期277-280,共4页Chinese Journal of Experimental Surgery

基　　金：河南省医学科技攻关计划项目（200903137）

摘　　要：目的探讨过氧化物酶体增殖物激活受体γ（PPARγ）激动剂吡格列酮（PIO）对代谢综合征大鼠骨髓内皮祖细胞（EPCs）黏附能力的影响及其机制。 方法建立代谢综合征大鼠模型，使用密度梯度离心法及差速贴壁法联合的方法培养代谢综合征大鼠骨髓EPCs，并使用双荧光染色的方法进行鉴定。用细胞计数法对正常对照组（NC组）、代谢综合征组（MS组）、PIO组等3组大鼠骨髓EPC黏附能力进行比较。将体外培养7 d的代谢综合征大鼠骨髓EPCs分5组：空白对照组、PIO干预组、PIO及PPARγ拮抗剂GW9662干预组、PIO及磷酸肌醇3激酶（PI3K）/蛋白激酶B（Akt）通道阻滞剂Wortmannin干预组、PIO及ERK通道阻滞剂PD98059干预组；检测EPCs的黏附。 结果代谢综合征组较正常对照组贴壁EPCs数量明显减少[（21.13±2.77）个比（33.20±3.06）个，t＝3.516，P＝0.000]；PIO组较代谢综合征组贴壁EPCs数量增多[（27.16±2.27）个比（21.13±2.77）个，t＝2.917，P＝0.007]。PIO可明显改善体外培养的代谢综合征大鼠骨髓EPCs黏附[（35.50±3.56）个比（21.30±2.78）个，t＝4.512，P＝0.006]，PPARγ拮抗剂GW9662和PI3K/Akt通道阻滞剂Wortmannin干预均可减弱PIO的促EPCs黏附作用[（22.50±3.16）个比（35.50±3.56）个，t＝4.512，P＝0.006；（23.10±3.11）个比（35.50±3.56）个，t＝4.011，P＝0.008]，而ERK通道阻滞剂PD98059不能减弱PIO的促EPCs黏附作用[（34.90±3.46）个比（35.50±3.56）个，t＝0.355，P＝0.211]。 结论代谢综合征大鼠骨髓EPCs黏附能力减弱，PIO可促进代谢综合征大鼠骨髓EPCs的黏附，这种作用可能是通过PI3K/Akt信号通路介导。Objective To explore whether peroxisome proliferator activated receptor γ（PPARγ） agonists pioglitazone （PIO） could affect the adhesion ability of endothelial progenitor cells （EPCs） from bone marrow in a rat model of metaboic syndrome, and further to explore the mechanism in vivo and ex vi- vo. Methods Diet - induced rat model of metaboic syndrome was established. EPCs were cultured using density gradient centrifugation and differential velocity adherent methods, and identified with double dyeing method. The adhesion ability of EPCs from bone marrow was compared by cell counting method among three groups incuding control group, metaboic syndrome group and PIO group. EPCs from bone marrow of rats with metaboic syndrome were cultured for 7 days, then were divided into 5 groups, respectively given PIO; PIO and PPAR antagonists GW9662; PIO and phosphatidylinositol 3 kinase （PI3K）/protein kinase B （Akt） channel blocker Wortmannin; PIO and extracellular signal -regulated kinase （ERK） channel bloc- ker PD98059, and a blank control group. Then the adhesion ability of EPCs was tested. Results As compared with the blank control group, the adhesion ability of EPCs was decreased in metaboic syndrome group （21.13±2. 77 vs. 33.20 ±3.06, t =3. 516, P =0. 000）. PIO treatment could improve the adhesion ability of EPCs （27. 16 ± 2. 27 vs. 21.13 ± 2. 77, t = 2. 917, P = 0. 007）. Ex vivo studies also showed PIO could improve the adhesion ability of EPCs cultured for 7 days （35.5 ± 3.56 vs. 21.3 ± 2. 78, t = 4. 512, P = 0. 006）. The effect disappeared when there were PPAR -γ antagonist GW9662 and PI3K/Akt channel blocker Wortmannin （22. 50 ± 3.16 vs. 35.50 ± 3.56, t = 4. 512, P = 0. 006 ; 23.10 ± 3.11 vs. 35.50 ± 3.56, t =4. 011, P= 0.008）, but the effect didn＇t disappare when there was ERK channel blocker PD98059 （34.90±3.46 vs. 35.50±3.56, t=0.355, P=0.211）.Conelusion The EPCs adhesion ability was decreased in rat model of metaboic syndrome. PIO could improve EPCs adhesio

关 键 词：内皮祖细胞 代谢综合征 吡格列酮 黏附 磷酸肌醇3激酶/蛋白激酶B 

分 类 号：R589[医药卫生—内分泌]