高压氧辅助治疗进行性肌营养不良的探索

发布时间：2018-03-30 13:44

  本文选题：进行性肌营养不良　切入点：高压氧治疗　出处：《吉林大学》2014年硕士论文

【摘要】：背景： 进行性肌营养不良（Progressive muscular dystrophy PMD）是一组遗传性肌肉变性疾病，临床特征主要为缓慢进行性加重的对称性肌肉无力和萎缩，一般无感觉障碍。PMD预后差，迄今无特异性治疗，主要的治疗方法有免疫抑制剂、成肌细胞移植、基因治疗、生长激素和胰岛素样生长因子等。目前国际上得到肯定的治疗是应用糖皮质激素治疗，但由于应用时间长副作用较大很难被患者所接受，而成肌细胞移植及基因治疗等尚不成熟，因此探索肌营养不良的辅助治疗迫在眉睫。据文献报道，高压氧治疗可以增加血氧含量及血氧分压，增加组织的储氧量，提高组织内毛细血管氧的弥散能力，减少L-型钙通道数量,抑制钙内流；高压氧治疗可以诱导基础成纤维细胞和实质细胞生长因子表达，增加大鼠缺血肢体的血流量和改善肌肉重塑；高压氧治疗可以减轻实验鼠缺血心肌损伤；糖尿病性心肌病经高压氧治疗后心肌细胞超微结构异常得到明显改善；本课题将高压氧作为进行性肌营养不良的辅助治疗，观察治疗前后临床症状及实验室检查的变化。 目的： 分析初步探索高压氧治疗对进行性肌营养不良的疗效，通过动物模型及临床试验，经统计分析来探讨高压氧治疗进行性肌营养不良的疗效，将高压氧作为进行性肌营养不良的辅助治疗，可延长患者生存期，提高生活质量。资料与方法： 动物实验部分： 选取40只Wistar雄性大鼠，采取钳夹坐骨神经制造周围神经损伤导致肌肉失神经萎缩的模型，随机分3组，分别为手术后正常饲养（A组）；药物对照组（B组）；药物高压氧综合治疗组（C组）。各组进行相应处理2个疗程（1个疗程为10天）后，对各组大鼠进行坐骨神经功能指数、斜坡实验及腓肠肌湿重改变等指标评估。并通过病理学检查对神经纤维及肌肉纤维的相关数据进行统计学分析。 临床试验部分： 研究对象为2007年6月至2013年11月间在吉林大学第一医院神经内科门诊和住院的25例患者进行回顾性分析，其中8例行高压氧及药物综合治疗，8例行药物治疗，9例放弃治疗的患者。对患者的一般资料（性别、年龄）、临床表现、实验室检验结果等进行收集和整理，采用门诊、住院、电话、邮寄随访方式，随访患者治疗前后的临床症状改善情况及检验结果的改变情况。 结果： 1.动物实验部分：坐骨神经功能指数：药物治疗组（B组）及高压氧药物综合治疗组（C组）的SFI均较空白对照组（A组）有明显恢复，与A组相比较，B、C组均有统计学意义，B组与A组比有统计学意义（P0.05）；C组与A组比有显著统计学意义（P0.01）；C组与B组比有统计学意义（P0.05）。斜坡实验：B组及C组的斜坡角度均大于A组，C组与A、B组比有显著统计学意义（P0.01）；B组与A组比有统计学意义（P0.05）。腓肠肌湿重比率：B组及C组的腓肠肌湿重比率均大于A组，C组与A组比有显著统计学意义（P0.01）；B组与A组相比有统计学意义（P0.05）。肌纤维横截面积测定：B组及C组治疗后肌纤维横截面积均大于A组，，B组与A组比有统计学意义（P0.05）；C组与A组、B组比有显著统计学意义（P0.01）。坐骨神经有髓神经纤维计数：治疗后观察有髓纤维的分布，B、C两组有髓纤维分布密度均较A组密集，与B组比C组变化更明显（见彩图图4.2）。两外通过有髓纤维的面积、直径及周长进行计数统计，B组与A组比有统计学意义（P0.05）；C组与A组、B组比有显著统计学意义（P0.01）。 2.临床试验部分:治疗后患儿均自觉下肢力量较前有所改善，7米的步行时间及蹲起时间缩短。在随后一年的随访中，有两名患者每隔1-2个月行高压氧治疗一疗程，在此期间患者的临床症状未见明显进展，而其他放弃此治疗的患者病情逐渐进展，有4名患者已丧失行走能力。两治疗组治疗前后肌酸激酶、乳酸脱氢酶及-羟丁酸脱氢酶数据进行统计分析，高压氧药物综合治疗组及药物治疗组与对照组比较其之间差异显著（p0.01），高压氧药物综合治疗组与药物治疗组之间差异亦具有显著统计学意义（p0.01）。 结论：高压氧药物综合治疗对受损的肌肉及周围神经有修复作用，且明显优于药物治疗组，在临床试验观察中，高压氧治疗后可改善患者的临床症状，提高肢体肌力，明显降低患者血清心肌酶学的改变，且长期间断高压氧辅助治疗可大大延缓患者的瘫痪的时间并可提高患者的生活质量。
[Abstract]:Background:
Progressive muscular dystrophy (Progressive muscular dystrophy PMD) is a group of hereditary muscle degenerative diseases, the main clinical features of slowly progressive symmetrical muscle weakness and atrophy, generally no sensory disturbance.PMD poor prognosis, so far no specific treatment, the main treatment with immunosuppressive agents, myoblast transplantation, gene treatment of growth hormone and insulin-like growth factor. The positive treatment is the application of glucocorticoid treatment, but side effects due to the long application time it is difficult to accepted by the patients, and myoblast transplantation and gene therapy is still not mature, so the exploration of imminent adjuvant treatment of muscular dystrophy. According to reported that hyperbaric oxygen therapy can increase blood oxygen content and oxygen partial pressure, increasing tissue oxygen storage capacity, improve the dispersion ability of capillary oxygen within the organization, reduce the L- type calcium channel The number of inhibition of Ca2 + influx; hyperbaric oxygen therapy and fibroblast growth factor expression induced by parenchymal cells, increase blood flow and improve muscle remodeling in rat limb ischemia; hyperbaric oxygen therapy can alleviate the myocardial injury of rats after ischemia; diabetic cardiomyopathy by high pressure oxygen treatment after myocardial ultrastructure abnormality was significantly improved this topic will be; hyperbaric oxygen as adjuvant treatment of muscular dystrophy, changes were observed before and after treatment of clinical symptoms and laboratory examination.
Objective:
Preliminary analysis of hyperbaric oxygen therapy on the curative effect of muscular dystrophy by animal models and clinical trials, statistical analysis to explore the effect of hyperbaric oxygen in the treatment of muscular dystrophy, hyperbaric oxygen as adjuvant treatment of muscular dystrophy, can prolong the survival of the patients, and improve the quality of life. Methods:
Animal experiment part:
A total of 40 Wistar male rats by clamping sciatic nerve atrophy of denervated muscle producing peripheral nerve model lead to injury, were randomly divided into 3 groups, respectively, after the operation of normal feeding (group A); drug control group (group B); drug hyperbaric oxygen treatment group (C group). Each group is processed in 2 a course of treatment (1 days after treatment for 10) of the sciatic nerve function index in rats, evaluate slope experiment and gastrocnemius wet weight change index. And through the pathological examination data on nerve fibers and muscle fibers were analyzed.
Clinical trial Part:
The object of the study is from June 2007 to November 2013 in No.1 Hospital of Jilin University of Neurology out-patient and hospitalization of 25 patients were retrospectively analyzed, including 8 cases of hyperbaric oxygen and drug treatment, 8 cases of drug treatment, 9 patients abandoned the treatment of patients. The general data of patients (gender, age), clinical manifestations, laboratory test results etc. collect and collate the outpatient, hospital, telephone, mail follow-up, changes of clinical symptoms of patients before and after treatment were improved and the test results.
Result锛

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