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自体骨髓单个核细胞治疗脊髓损伤的临床研究

Clinical Study of Autologous Bone Marrow-derived Mononuclear Cell Transplantation in Patients with Spinal Cord Injury

【作者】 崔贵祥

【导师】 岳寿伟;

【作者基本信息】 山东大学 , 康复医学与理疗学, 2009, 硕士

【摘要】 目的研究证明,骨髓来源的单个核细胞(bone marrow-derivedmononuclear cells,MNCs)所包含的多种骨髓干细胞可作为多潜能干细胞对脊髓外伤或缺血性损伤等造成的功能缺失具有显著的治疗作用。康复训练对于脊髓损伤患者肌力、日常生活活动能力以及膀胱功能等神经功能的改善具有一定作用,但对脊髓损伤的修复作用有限。本文采用自体骨髓单个核细胞移植方法结合康复训练治疗脊髓损伤患者,观察其近期疗效和安全性。方法34例脊髓损伤患者,采用随机表法分为移植组和对照组。移植组16例,对照组18例,均经CT或MRI确诊并行手术或非手术治疗。感觉、运动功能评定采用美国脊柱损伤协会(American Spinal InjuryAssociation,ASIA)分级,脊髓损伤程度采用脊髓损伤神经学分类国际标准(International Standards for Neurological Classification of SpinalCord Injury)(第六版,2006)进行评定。两组在年龄、病程、损伤程度等方面均具有可比性(P>0.05)。患者知情同意并签署知情同意书。移植组在综合康复治疗的基础上给予自体MNCs治疗,经髂骨穿刺采集自体骨髓,分离提取MNCs后经静脉或蛛网膜下腔注射,同时静脉滴注复方丹参20mL。对照组在综合康复治疗的基础上给予生理盐水250mL,静脉滴注。两组均于入院当天、治疗后7,15,30,60,90d进行运动与感觉功能、日常生活活动能力、膀胱功能评定。结果①移植组感觉、运动功能、日常生活活动能力和膀胱功能均有改善,但与对照组比较,统计学差异无显著性意义。②ASIA分级评定:移植组ASIA分级A级9例,有2例在第90天评估中恢复为B级。B级3例,1例在第90天评估中恢复为C级。C级2例,1例在第30天评估中恢复为D级,第90天评估中恢复为E级,能独立行走,生活完全自理。D级2例,其中1例在第90天评估中恢复为E级。对照组A级8例,1例在第90天评估中恢复为B级。B级5例,治疗后无变化。C级3例,1例在第90天评估中恢复为D级。D级2例,在第90天评估中恢复为E级。两组其余患者治疗后ASIA分级无变化。两组比较,经Ridit分析,u=0.07,P=0.94,差异无显著性意义。③日常生活活动能力评分:采用改良Bathel指数(Modified Bathel Index,MBI)。经过干细胞移植治疗和系统康复训练,与治疗前相比,移植组(F=57.31)和对照组(F=52.08)患者的MBI评分均有显著提高,经统计学处理,均P<0.001,差异有显著性意义。但两组之间比较无差异(P>0.05)。④膀胱功能:移植组12例恢复自主排尿,时间平均为(56.7±8.6)d,对照组9例,平均为(61.3±7.9)d,两组比较经统计学处理,P>0.05,差异无显著性意义;移植组患者有8例出现尿失禁,6例在治疗后15d、2例在第30天评估时症状消失,对照组8例,在第90天评估时3例症状消失,5例无变化。采用间歇清洁导尿方法训练膀胱功能,两组患者残余尿量均有显著减少,治疗前、后比较,均P<0.001,差异有非常显著性意义。但两组之间比较无差异;⑤MNCs移植的不良反应,包括蛛网膜下腔移植后出现低热9例,头痛4例,腹胀1例:1例患者在注射后出现双下肢麻木、脑膜刺激征。经对症处理均于72小时内消失。结论自体骨髓MNCs移植治疗脊髓损伤近期有一定疗效,安全可行。

【Abstract】 Objective To observe the short-term curative effect and safety of autologous bone marrow-derived mononuclear cells (MNCs) transplantation on patients with spinal cord injury (SCI).Methods Total 34 inpatients with SCI were randomly divided into transplantation group and control group. The patients knew the experiment and signed the consent. A total of 16 cases in the transplantation group and 18 cases in the control group were diagnosed with CT or MRI. It was comparable between the two group in age, course of disease, degree of injury (ASIA rating) (P>0.05). On the basis of comprehensive rehabilitation treatment, those in the transplantation group received autologous MNCs transplantation. The bone marrow (160-280mL) was harvested from the patients’ ilia and then MNCs were isolated. The MNCs were injected intravenously or into subarachnoid space by lumbar puncture. Those in the control group received comprehensive rehabilitation treatment and NS 250mL intravenously. Motor and sense function, activity of daily living (ADL) and bladder function were evaluated on the first day of rehabilitation, 7,15,30,60 and 90 days after treatment in the two groups. Neurological function of the patients with spinal cord injury were evaluated by American Spinal Injury Association (ASIA) and International Standards for Neurological Classification of Spinal Cord Injury (Edit 6th, 2006).Results Totally 34 patients were involved in the result analysis.①After transplantation of MNCs and rehabilitation treatment, the scales of sense, motor and autonomic nerve function were improved to some extent in 16 patients of transplantation group and 18 of control group. There were no significant differences statistically between the two groups in scales of the sense, motor, MBI and bladder function.②In the transplantation group, there were 5 cases elevated 1-2 grades respectively on the 90th day, In the control group, there were 4 cases elevated 1 grade respectively on the 90th day. But there were no significant differences statistically by Ridit analyses(u=0.07, P=0.94).③The side-effects of the MNCs transplantation included fever (9 cases), headache (4 cases), and abdominal dissension (1 cases). Of them, 1 case appeared numbness in his legs and meningeal stimulation after subarachnoid space injection, and disappeared within two or three days.Conclusion MNCs transplantation in the treatment of SCI is effective and safe in short term, but long-term curative effect needs more observation.

  • 【网络出版投稿人】 山东大学
  • 【网络出版年期】2011年 S1期
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