【作者】 曾昭凡；

【导师】 唐新华；

【作者基本信息】 南昌大学 ， 外科学， 2010， 硕士

【摘要】 目的:探讨自体骨髓干细胞移植在治疗下肢慢性缺血性疾病的临床应用以及对其安全性和疗效的评价;探讨下肢肌内注射法移植与动脉血管腔内注射法移植之间的疗效差别。方法:分析2008年1月至2009年6月血管外科收治的下肢慢性缺血性疾病患者40例共计肢体40条(双下肢患者计病重侧),男32例,女8例,男女比例4∶1,年龄31~87岁,平均(68.2±7.1)岁。其中单纯下肢动脉硬化闭塞症(ASO)21例,糖尿病合并下肢动脉硬化(DF)15例,血栓闭塞性脉管炎(TAO)4例。临床症状包括疼痛37例,冷感39例,麻木29例,溃疡坏疽23例,跛行40例。按Fontaine分级:Ⅱ级6例,Ⅲ级11例,Ⅳ级23例。患者均经正规的非手术方法治疗半年以上无效。40例患者按移植方法的不同随机均分为下肢肌内局部注射组(第1组)和动脉血管腔内注射组(第2组)。糖尿病患者空腹血糖控制在7.0mmol/L以下,非空腹血糖控制在10.0mmol/L以下,糖化血红蛋白(HbAlc)控制在6.5%以下。患者在抽取骨髓前均使用人粒细胞集落刺激因子(G-CSF)刺激动员骨髓细胞2~3d,300μg/d ,动员末日抽取骨髓血200ml,经密度梯度离心法分离提纯后获得骨髓单个核细胞悬浊液,按上述两种方法移植入患肢(双下肢患者选取病重侧)。术后仍辅于抗血小板、扩血管等常规治疗。密切随访6个月,每月定期随访主观症状变化情况,6个月后复查皮温、经皮氧分压(TcPO2)、踝肱指数(ABI)、血管数字减影造影(DSA),记录疼痛、冷感、麻木、跛行距离,观察溃疡情况。采用SPSS16.0统计软件进行数据处理,治疗前后对比采用配对数据均数t检验,两组间疗效对比采用方差检验,检验水准ɑ=0.05。结果:移植治疗后6个月,所有患者获得随访,各观察指标均进入统计学分析。两组辅助检查指标(皮温、侧支循环、TcPO2)及临床症状指标(疼痛、冷感、麻木、溃疡、跛行)移植治疗前后差异均有统计学意义(P<0.01)(表1、表2、图表2)。其中4例患者移植治疗后6个月侧支循环明显丰富(附图2.1.1~2.1.4),3例患者移植治疗后6个月溃疡创面愈合良好(附图2.2.1~2.2.3)。两组临床症状各指标评分及侧支循环再生程度评分示移植治疗总有效率均≥60%(表3、图表1)。两组ABI变化均不明显,移植治疗前后差异无统计学意义(P>0.05)(表1)。两组移植治疗后所有观察指标差异均无统计学意义(P>0.05)(表4),两组间疗效无明显差别。结论:自体骨髓干细胞无论是采取下肢肌内局部注射法移植还是采取动脉血管腔内注射法移植治疗下肢慢性缺血性疾病均是一种简单、安全、有效的方法,两种移植方法疗效无明显差别。经动员刺激后的自体骨髓干细胞移植有抽取骨髓少,细胞含量多及安全性高等优点。更多还原

【Abstract】 Objective: To probe into the application of autologous bone marrow stem cells transplantation in the treatment of chronically ischemic disease of lower extremity and evaluate the security and curative effect.Secondly, to probe into the difference of curative effect between Intramuscular transplantation and Endovascular transplantation.Methods: 40 patients with chronically ischemic lower limb had been treated since January 2008 to June 2009. Among them, 32 males, 8 females; aged 31~87 years, averaged (68.2±7.1) years. Of the 40 patients, 21 diagnose atherosclerosis obliterans, 15 diagnose diabetic foot and 4 diagnose thromboangiitis obliterans. 37 had pain symptom, 39 had cold symptom, 29 had numbness symptom , 23 had ulcer symptom, 40 had intermittent claudication symptom. 6 patients were in FontaineⅡ, 11 patients were in FontaineⅢ, 23 patients were in FontaineⅣ. All patients had been defeated from standard medicamentous cure. By difference of transplantation means, divided equally 40 patients into Intramuscular transplantation group (the first group) and Endovascular transplantation group (the second group). The fasting blood glucose of diabetic must be controlled below 7.0mmol/L, and the non-fasting blood glucose must be controlled below 10.0mmol/L, and the HbAlc must be controlled below 6.5%. The bone marrow of each patient was stimulated by an injection of the recombinant human granulocyte macrophage colony-stimulatory factor(G-CSF), 300μg/d, for 2～3days. Upon completion of stimulation, the bone marrow 200ml was drawn from the iliac spine and the stem cells were obtained, after disassociated and depuated, transplanting into the more severely ischemic limb. Antiplatelet therapy and Vasodilator therapy must be continued, and they were followed once a month after the transplantation. The skin temperature, transcutaneous oxygen pressure(TcPO2), digital subtraction angiography(DSA)and ankle/brachia index (ABI) were rechecked at 6 months later, and the symptoms of pain, cold, numbness, intermittent claudication and physical signs of ulcer and gangrene were evaluated. SPSS16.0 statistical software were used for datum processing. The curative effect before and after treatment were compared using paired t-test. The curative effect between two groups were compared using Variance-test. Test level as :ɑ=0.05.Results: Six months later, all of 40 patients were involved in the analysis of result. The indexes of the two groups of auxiliary examination and clinical symptoms before and after treatment had statistical significance((P<0.01) (table 1, table 2, chart 2). Among them, 4 patients had rich Collateral Circulation (image2.1.1~2.1.4), and 3 patients had ulcer healing well after transplantation (image2.2.1~2.2.3 ). The total effective rate of clinical symptoms and Collateral Circulation of two groups are larger than 60%(table 3, chart 1). ABI before and after treatment are all no statistical significance (P>0.05)(table 1). All of the indexes are no significant difference between the two groups((P>0.05))(table 4).Conclusion: transplantation of autologous bone marrow stem cells is effective in the treatment of chronically ischemic disease of lower limb. which is a simple, safe and effective treatment for chronically ischemic disease of lower limb. There is no significant difference of curative effect between Intramuscular transplantation and Endovascular transplantation. The mobilization stimulated bone marrow stem cells transplantation has advantages of taken a less bone marrow, obtained a larger amount cells and had a high security.更多还原