Tan Q, Li G P, Wang Q S, Zheng C H, Zhang S Y
Department of Cardiology, the First Hospital of Qinhuangdao, Qinhuangdao 066000, China.
Zhonghua Yi Xue Za Zhi. 2017 Jul 25;97(28):2186-2193. doi: 10.3760/cma.j.issn.0376-2491.2017.28.006.
To explore whether diabetes mellitus (DM) impairs functions of bone marrow-derived endothelial progenitor cells (BM-EPC) and circulating EPC. Diabetic model of rabbit was induced by Alloxan injection and the rabbits were then randomly divided into three groups: BM-EPC group, circulating EPC group, and DM group, with six rabbits in each group. Another 6 normal rabbits were enrolled as normal control group as well. 8 weeks later, BM-EPC and circulating EPC from diabetic and healthy rabbits were isolated and cultured. Colony number, proliferation, adhesion and tube formation function were detected. Exogenous diabetic BM-EPC and circulating EPC were analyzed for therapeutic efficacy in acute ischemia model of diabetic rabbits. Left ventricular (LV) function was assessed using Echocardiography. Capillary density and fibrosis area were evaluated by confocal laser scanning microscope (CLSM) and Masson-trichrome staining. The mRNA expression of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) was analyzed using real-time quantitive PCR. Colony number, proliferation, adhesion and tube formation function of diabetic circulating EPC were significantly reduced compared with healthy rabbits. DM impaired tube-forming ability of BM-EPC, but did not influence colony number, proliferation and adhesion function. Compared with circulating EPC and control group, BM-EPC group had fewer fibrosis area (6.98%±0.94% vs 13.03%±2.97% and 15.84%±4.74%, both =0.001), higher capillary density [(792±87) vs (528±71) and (372±77) vessels/mm(2,) both <0.001], higher mRNA expression of VEGF (6.25±2.33 vs 2.19±1.01 and 1.55±0.52, both <0.001) and bFGF (6.38±2.65 vs 1.24±0.76 and 1.18±0.82, both <0.001), higher left ventricular ejection fraction (LVEF) (61%±4% vs 47%±5% and 50%±10%, both <0.05). DM not only impaired functions of circulating EPC, but also influenced tube formation function of BM-EPC. Auto transplantation of BM-EPC may rescue the ischemic myocardium by neovascularization and paracrine effect in diabetic rabbits.
探讨糖尿病（DM）是否会损害骨髓来源的内皮祖细胞（BM-EPC）和循环内皮祖细胞（EPC）的功能。通过注射四氧嘧啶诱导兔糖尿病模型，然后将兔随机分为三组：BM-EPC组、循环EPC组和DM组，每组6只兔。另选6只正常兔作为正常对照组。8周后，分离并培养糖尿病兔和健康兔的BM-EPC和循环EPC。检测集落数、增殖、黏附及成管功能。分析外源性糖尿病BM-EPC和循环EPC对糖尿病兔急性缺血模型的治疗效果。采用超声心动图评估左心室（LV）功能。通过共聚焦激光扫描显微镜（CLSM）和Masson三色染色评估毛细血管密度和纤维化面积。采用实时定量PCR分析血管内皮生长因子（VEGF）和碱性成纤维细胞生长因子（bFGF）的mRNA表达。与健康兔相比，糖尿病循环EPC的集落数、增殖、黏附及成管功能显著降低。DM损害BM-EPC的成管能力，但不影响集落数、增殖及黏附功能。与循环EPC组和对照组相比，BM-EPC组的纤维化面积较少（6.98%±0.94% 对13.03%±2.97% 和15.84%±4.74%，均P=0.001），毛细血管密度较高[（792±87）对（528±71）和（372±77）个血管/mm²，均P<0.001]，VEGF（6.25±2.33对2.19±1.01和1.55±0.52，均P<0.001）和bFGF（6.38±2.65对1.24±0.76和1.18±0.82，均P<0.001）的mRNA表达较高，左心室射血分数（LVEF）较高（61%±4%对47%±5%和50%±10%，均P<0.05）。DM不仅损害循环EPC的功能，还影响BM-EPC的成管功能。BM-EPC自体移植可能通过新生血管形成和旁分泌作用挽救糖尿病兔的缺血心肌。
