腺病毒转染的肝细胞生长因子对冠心病患者外周造血干细胞的动员作用

Effect of intracoronary adenovirus vector encoding hepatocyte growth factor gene on hematopoietic stem cells mobilization in patients with extensive coronary heart disease

目的探讨经冠状动脉内注射腺病毒(adenovirus,Ad_5)转染人肝细胞生长因子(HGF)对严重冠状动脉狭窄患者外周造血干细胞的动员作用。方法本研究入选18例冠心病患者,分为两组:给药组9例,经冠状动脉注入Ad_5-HGF;对照组9例,经冠状动脉注入同等量的生理盐水。所有患者均于冠状动脉造影术前、术后6 h、24 h 及6天抽取外周血,并应用流式细胞仪单克隆荧光抗体标记法检测其外周造血干细胞表面抗原 CD34^+、CD38^+及 CD117^+。结果给药组术后6 h 的 CD34^+明显高于对照组(0.104±0.082比0.022±0.012,P=0.021),0 h、24 h 及6天的 CD34^+两组之间差异无统计学意义;给药组术后6天的 CD117^+明显高于对照组(0.058±0.058比0.012±0.009,P=0.034),差异有统计学意义,其余时间点两组间差异均无统计学意义;CD38^+在各时间点两组间差异均无统计学意义。结论经冠状动脉内注射转染 Ad_5-HGF 可能在短时间内引起外周造血干细胞的动员。动员外周造血干细胞可能是 HGF 参与血管新生和器官组织损伤修复及抗凋亡、改善心功能的一个重要机制。

Objective To investigate the effect of intracoronary adenovirus vector encoding hepatocyte growth factor gene （Ads-HGF） on hematopoietic stem cells mobilization in patients with extensive coronary heart disease. Methods Patients with extensive coronary heart disease were treated with intracoronary infusion of adenovirus vector encoding hepatocyte growth factor （ Ad5-HGF 5× 10^9 pfu） gene plus stent implantation （n = 9） or equal physiological saline plus stent implantation （ n = 9）. Angioplasty and stent implantation was performed according to standard clinical practice by the femoral approach and blood samples were drawn from each patient at baseline before PCI, 6 to 24 hours and 6 days post procedure. The number of CD34^＋, CD38^＋ and CD117^＋ cells in peripheral blood was analyzed by flow cytometer. Results The number of circulating CD34^＋ cells in Ads-HGF gene treatment group 6 hours after procedure and the number of circulating CD117 ^＋ cells 6 days post procedure were significantly higher in Ad5-HGF gene treatment group than those in the control group （ 0. 104 ＋ 0, 082 vs. 0. 022 ＋ 0. 012, P = 0.021） and （0.058 ＋0.058 vs. 0.012 ＋0. 009,P =0.034）, respectively. Conclusion Intracoronary administration of Ad5-HGF could mobilize hematopoietic stem cells into peripheral blood and the consequent role of this observation on myocardial regeneration warrants further detailed studies.