肝细胞生长因子基因联合骨髓间充质干细胞治疗糖尿病周围动脉硬化闭塞症及糖尿病足近期观察

摘要

Objective To investigate the clinical effect about the gene therapy for peripheral arterial disease (PAD) and the diabetic foot ulcer(DFU) using plasmid DNA encoding human hepatocyte growth factor(HGF)gene.Methods Totally Thrity cases who had suffered from the PAD in diabetes with grade of Fontaine Ⅲ ～ Ⅳ were selected.30 cases were divided into two groups at random,open,control study,which is A and B group.Sixteen cases were in group A,namely study group.Forteen cases were in group B,namely control group.A group's patients were injected the human HGF plasmid DNA( HGF-PVAX1 )4 mg combining with the bone marrow stem cell into gastrocnemius.B group's patients were accepted the injection of bone marrow stem cell into gastrocnemius merely.We compared the clinical curative effect after the injection of the stem cell into gastrocnemius before and l,3,6 months after the stem cell transplantation operation.Results Symptom of the intermittence elaudication of patients in both groups was improved.In group A,the ankle brachial index (ABI) was (0.346 ± 0.036) and (0.596 ± 0.036) before and 6 months after the operation,while in group B,the ABI was (0.379 ± 0.031 ) and (0.468 ± 0.032).Skin temperature of lower extremities and dorsal feet was obviously improved after the transplantation.In A group,the average skin temperature was (33.4 ± 2.1 ) ℃C before and ( 35.9 ± 1.8 ) ℃C after the operation.Meanwhile,it was (33.7 ± 1.5 ) ℃ before and (33.1 ± 1.3 ) ℃ after the operation.A review by color Doppler ultrasound on lower extremity arteries was performed to all patients 3 months after the operation.There was no significant changes at superficial femoral and popliteal arteries.In A group,there were 8 cases' blood flow in dorsal artery before the operation were greater than or equal to 20 ml/min,4 were 15-19 ml/min,2 were 1-14 ml/min,2 without detectable blood flow; after the operation,there were 10,2,2 and 2 cases at the corresponding levels.In B group,there were 6 cases' blood flow in dorsal artery before the operation were greater than or equal to 20 rml/min,3 were 15-19 ml/min,3 were 1-14 ml/min,2 without detectable blood flow; after the operation,there were 7,2,3 and 2 cases at the corresponding levels.Blood flow in A group was better than that in B group( P ＜ 0.05 ).The incidence rate of the untoward effect had no statistical significance between the two groups.Conclusions Gastrocnemius injection of human HGF plasmid DNA( HGF-PVAX1 ) combined with the bone marrow stem cell can improve the limb ischemia at certainly extent.It will be a new method of treating PAD.%目的 探讨利用肝细胞生长因子(HGF)基因联合骨髓间充质干细胞治疗糖尿病周围动脉硬化闭塞症(PAD)和糖尿病足的临床疗效.方法 将Fontaine分级Ⅲ～Ⅳ级的糖尿病PAD及糖尿病足患者30例完全随机分为2组.研究组(16例)采用携带人HGF基因的质粒DNA( HGF-PVAX1 )4 mg联合骨髓动员后的于细胞,局部注射于患肢腓肠肌；对照组(14例)于患肢腓肠肌局部注射单纯骨髓动员后的于细胞.分别于移植术后1、3、6个月比较2组在干细胞局部注射治疗前后的临床疗效.结果 2组患者间歇性跛行有好转.研究组术前与术后6个月的下肢踝/肱指数(ABI)分别为(0.346±0.036)、(0.596±0.036),对照组是(0.379±0.031)、(0.468±0.032).2组术后与术前相比,差异均有统计学意义(均P＜0.05)；术后研究组ABI水平高于对照组,差异亦有统计学意义(P＜0.05).研究组术后皮温平均为(35.9±1.8)℃,术前为(33.4±2.1)℃；对照组术后皮温平均为(33.1±1.3)℃,术前为(33.7±1.5)℃.2组皮温变化程度比较,差异有统计学意义(P＜0.05).2组移植后3个月复查下肢动脉彩色超声,股浅动脉、腘动脉未见明显变化.研究组移植前足背动脉血流量≥20 ml/min者8例,15 ～ 19 ml/min者4例,1～ 14 ml/min者2例,0 ml/min者2例；移植后≥20 ml/min者10例,15 ～ 19 ml/min者2例,1～14 ml/min者2例,0ml/min者2例.对照组移植前足背动脉血流量≥20 ml/min者6例,15～19 ml/min者3例,1～14 ml/min者3例,0ml/min者2例；移植后≥20 ml/min者7例,15～19 ml/min者2例,l～ 14 ml/min者3例,0 ml/min者2例.研究组移植后足背动脉血流量改善情况好于对照组,差异有统计学意义(P＜0.05).2组间不良反应发生率差异无统计学意义.结论 注射HGF-PVAXl联合骨髓干细胞移植可在一定程度上改善肢体缺血,可能成为治疗PAD的一种新手段.但其远期疗效和安全性还有待观察.