【作者】 吴石白； 关小宏； 王恒湘；

【Author】 WU Shi-bai;Guan Xiao-hong;Wang Heng-xiang;Department of Endocrinology,The Air Force Jeneral Hospital;

【机构】 解放军空军总医院内分泌科； 解放军空军总医院血液科；

【摘要】 目的:探讨利用肝细胞生长因子(hepatocyte growth factor,HGF)基因治疗糖尿病合并周围动脉闭塞硬化症(peripheral arterial disease,PAD)和糖尿病足(Diabtic foot ulcer,DFU)的临床疗效。方法:采取随机、开放、对照研究的方法,选取符合糖尿病合并PAD、Fontaine分级Ⅲ~Ⅳ级的患者28例,分为2组,A组为携带人HGF基因的质粒DNA(HGF-PVAX1)4mg联合骨髓动员后的干细胞,局部注射于患肢腓肠肌,共16例,B组为单纯骨髓动员后的干细胞,局部注射于患肢腓肠肌,共12例。比较2组在干细胞局部注射治疗前后的临床疗效。评价标准是主观评分加客观评分,主观评分包括静息痛评分、肢体冷感评分;客观评分包括跛行距离测定、下肢踝/肱指数(ABI)、皮温、下肢动脉MRI,观察时间点为术前、术后3月、6月、12月。结果:注射携带人HGF基因的质粒DNA(HGF-PVAX1)后,患者无过敏、水肿、视网膜病变加重等不适。A、B两组临床症状均有改善,A组的主观症状评分较B组改善明显,A组在术前、术后3月、6月、12月的静息痛评分分别是4分,2分,2分,2分,B组是4分,3分,2分,2分;肢体冷感评分A组分别是3分,1分,2分,1分,B组是3分,2分,2分,2分;A组的ABI术前与术后6月分别是(0.346±0.036)、(0.596±0.036),B组是(0.379±0.031)、(0.468±0.032);A组的皮温术后较术前平均提高2.9℃,B组的皮温术后较术前平均提高2.5℃;术后12月A组的下肢动脉MRI显示膝下侧枝循环数目较B组明显增多。结论:HGF是最强的促血管内皮生长因子,注射携带人HGF基因的质粒DNA(HGF-PVAX1)联合骨髓干细胞局部注射治疗,可有效改善患者的静息痛、肢冷的症状,提高皮温,改善间歇性跛行,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。远期疗效和安全性还有待观察。更多还原

【Abstract】 Objective: To investigate the clinical effect about the gene therapy for peripheral arterial disease(PAD) and the Diabetic Foot ulcer(DFU) ueing plasmid DNA encoding human hepatocyte growth factor(HGF) gene.Methods: To select the 28 cases who had suffered from the PAD in Diabetes and the grade of Fontaine was Ⅲ~Ⅳ.28 cases were divided into two groups at random,open,control study,which is A and B group. A group contain 16 cases patients in all,which making intramuscular injection of human HGF plasmid DNA(HGFPVAX1)4mg combining with the bone marrow stem cell into gastroc.B group contain 12 cases patients, which adopting intramuscular injection of bone marrow stem cell merely.We compared with the clinical curative effect after the intramuscular injection of the stem cell. The evaluation criterion is subjective score and objective score. The subjective score adopt the rest pain score and cold sense score in limbs. The objective score conain the evaluating the distance of the lame,ankle/branchium index(ABI),skin temperature, MRI of the artery of lower extremity.The period of the observing is preoperative and postoperative 3 monthes,6 mongthes, 12 monthes.Results: All patients hadn’t hypersensitiveness, oedema and retinopathy aggratate after the intramuscular injection of human HGF plasmid DNA(HGF-PVAX1). The clinical symptom had a improving both in A and B group. A group’s subjective score was improved obviously than B group’s. A group’s rest pain score was differencely 4,2,2,2 at preoperation, postoperation 3 monthes,6 monthes,12 monthes. B group’s rest pain score was 4,3,2,2. A group’s cold sense score was 3,1,2,1. B group’s cold sense score was 3,2,2,2. A group’s ABI was(0.346±0.036) and(0.596±0.036)at preoperation, postoperation 6monthes.Which B group’s ABI was(0.346±0.036) and(0.596±0.036). A group’s skin temperature increased 2.9℃ in average and B group’s increased 2.5℃ in average. A group’s amount of the collateral circulation below knee were obviously increasing. Conclusion: HGF is the most doughtyly factor of the blood vessel endothelium. Intramuscular injection of human HGF plasmid DNA(HGF-PVAX1) combining with the bone marrow stem cell can improve the limb ischemia at certainly extent.It would be a new method in treating PAD. It’s prostecdtive efficacy and security is not yet to observe.更多还原