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高壓氧輔助治療進(jìn)行性肌營養(yǎng)不良的探索

發(fā)布時間:2018-03-30 13:44

  本文選題:進(jìn)行性肌營養(yǎng)不良 切入點:高壓氧治療 出處:《吉林大學(xué)》2014年碩士論文


【摘要】:背景: 進(jìn)行性肌營養(yǎng)不良(Progressive muscular dystrophy PMD)是一組遺傳性肌肉變性疾病,臨床特征主要為緩慢進(jìn)行性加重的對稱性肌肉無力和萎縮,一般無感覺障礙。PMD預(yù)后差,迄今無特異性治療,主要的治療方法有免疫抑制劑、成肌細(xì)胞移植、基因治療、生長激素和胰島素樣生長因子等。目前國際上得到肯定的治療是應(yīng)用糖皮質(zhì)激素治療,但由于應(yīng)用時間長副作用較大很難被患者所接受,而成肌細(xì)胞移植及基因治療等尚不成熟,因此探索肌營養(yǎng)不良的輔助治療迫在眉睫。據(jù)文獻(xiàn)報道,高壓氧治療可以增加血氧含量及血氧分壓,增加組織的儲氧量,提高組織內(nèi)毛細(xì)血管氧的彌散能力,減少L-型鈣通道數(shù)量,抑制鈣內(nèi)流;高壓氧治療可以誘導(dǎo)基礎(chǔ)成纖維細(xì)胞和實質(zhì)細(xì)胞生長因子表達(dá),增加大鼠缺血肢體的血流量和改善肌肉重塑;高壓氧治療可以減輕實驗鼠缺血心肌損傷;糖尿病性心肌病經(jīng)高壓氧治療后心肌細(xì)胞超微結(jié)構(gòu)異常得到明顯改善;本課題將高壓氧作為進(jìn)行性肌營養(yǎng)不良的輔助治療,觀察治療前后臨床癥狀及實驗室檢查的變化。 目的: 分析初步探索高壓氧治療對進(jìn)行性肌營養(yǎng)不良的療效,通過動物模型及臨床試驗,經(jīng)統(tǒng)計分析來探討高壓氧治療進(jìn)行性肌營養(yǎng)不良的療效,將高壓氧作為進(jìn)行性肌營養(yǎng)不良的輔助治療,可延長患者生存期,提高生活質(zhì)量。資料與方法: 動物實驗部分: 選取40只Wistar雄性大鼠,采取鉗夾坐骨神經(jīng)制造周圍神經(jīng)損傷導(dǎo)致肌肉失神經(jīng)萎縮的模型,隨機(jī)分3組,分別為手術(shù)后正常飼養(yǎng)(A組);藥物對照組(B組);藥物高壓氧綜合治療組(C組)。各組進(jìn)行相應(yīng)處理2個療程(1個療程為10天)后,對各組大鼠進(jìn)行坐骨神經(jīng)功能指數(shù)、斜坡實驗及腓腸肌濕重改變等指標(biāo)評估。并通過病理學(xué)檢查對神經(jīng)纖維及肌肉纖維的相關(guān)數(shù)據(jù)進(jìn)行統(tǒng)計學(xué)分析。 臨床試驗部分: 研究對象為2007年6月至2013年11月間在吉林大學(xué)第一醫(yī)院神經(jīng)內(nèi)科門診和住院的25例患者進(jìn)行回顧性分析,其中8例行高壓氧及藥物綜合治療,8例行藥物治療,9例放棄治療的患者。對患者的一般資料(性別、年齡)、臨床表現(xiàn)、實驗室檢驗結(jié)果等進(jìn)行收集和整理,采用門診、住院、電話、郵寄隨訪方式,隨訪患者治療前后的臨床癥狀改善情況及檢驗結(jié)果的改變情況。 結(jié)果: 1.動物實驗部分:坐骨神經(jīng)功能指數(shù):藥物治療組(B組)及高壓氧藥物綜合治療組(C組)的SFI均較空白對照組(A組)有明顯恢復(fù),與A組相比較,B、C組均有統(tǒng)計學(xué)意義,B組與A組比有統(tǒng)計學(xué)意義(P0.05);C組與A組比有顯著統(tǒng)計學(xué)意義(P0.01);C組與B組比有統(tǒng)計學(xué)意義(P0.05)。斜坡實驗:B組及C組的斜坡角度均大于A組,C組與A、B組比有顯著統(tǒng)計學(xué)意義(P0.01);B組與A組比有統(tǒng)計學(xué)意義(P0.05)。腓腸肌濕重比率:B組及C組的腓腸肌濕重比率均大于A組,C組與A組比有顯著統(tǒng)計學(xué)意義(P0.01);B組與A組相比有統(tǒng)計學(xué)意義(P0.05)。肌纖維橫截面積測定:B組及C組治療后肌纖維橫截面積均大于A組,,B組與A組比有統(tǒng)計學(xué)意義(P0.05);C組與A組、B組比有顯著統(tǒng)計學(xué)意義(P0.01)。坐骨神經(jīng)有髓神經(jīng)纖維計數(shù):治療后觀察有髓纖維的分布,B、C兩組有髓纖維分布密度均較A組密集,與B組比C組變化更明顯(見彩圖圖4.2)。兩外通過有髓纖維的面積、直徑及周長進(jìn)行計數(shù)統(tǒng)計,B組與A組比有統(tǒng)計學(xué)意義(P0.05);C組與A組、B組比有顯著統(tǒng)計學(xué)意義(P0.01)。 2.臨床試驗部分:治療后患兒均自覺下肢力量較前有所改善,7米的步行時間及蹲起時間縮短。在隨后一年的隨訪中,有兩名患者每隔1-2個月行高壓氧治療一療程,在此期間患者的臨床癥狀未見明顯進(jìn)展,而其他放棄此治療的患者病情逐漸進(jìn)展,有4名患者已喪失行走能力。兩治療組治療前后肌酸激酶、乳酸脫氫酶及-羥丁酸脫氫酶數(shù)據(jù)進(jìn)行統(tǒng)計分析,高壓氧藥物綜合治療組及藥物治療組與對照組比較其之間差異顯著(p0.01),高壓氧藥物綜合治療組與藥物治療組之間差異亦具有顯著統(tǒng)計學(xué)意義(p0.01)。 結(jié)論:高壓氧藥物綜合治療對受損的肌肉及周圍神經(jīng)有修復(fù)作用,且明顯優(yōu)于藥物治療組,在臨床試驗觀察中,高壓氧治療后可改善患者的臨床癥狀,提高肢體肌力,明顯降低患者血清心肌酶學(xué)的改變,且長期間斷高壓氧輔助治療可大大延緩患者的癱瘓的時間并可提高患者的生活質(zhì)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錛

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