本文關(guān)鍵詞： 抗肌萎縮蛋白 抗肌萎縮蛋白相關(guān)蛋白 神經(jīng)元型一氧化氮合酶 肌營(yíng)養(yǎng)不良癥 免疫熒光　出處：《鄭州大學(xué)》2016年碩士論文　論文類型：學(xué)位論文

【摘要】：研究背景在歐盟,肌營(yíng)養(yǎng)不良癥的發(fā)病率為1/2000,病情進(jìn)展緩慢、致殘率高、預(yù)后差,目前尚無(wú)有效的治療手段,有關(guān)疾病診斷和治療方面的研究顯得尤為重要�？辜∥s蛋白(dystrophin)對(duì)維持肌纖維的結(jié)構(gòu)完整性具有重要作用,dystrophin基因突變引起Duchenne型肌營(yíng)養(yǎng)不良癥(DMD)和Becker型肌營(yíng)養(yǎng)不良癥(BMD)�？辜∥s蛋白相關(guān)蛋白(utrophin)是dystrophin的同源蛋白,兩種蛋白結(jié)構(gòu)高度相似,utrophin主要在再生肌纖維中表達(dá)并維持肌纖維結(jié)構(gòu)的完整性,在成熟肌纖維中幾乎全部被dystrophin替代,近年來(lái)通過(guò)動(dòng)物實(shí)驗(yàn)發(fā)現(xiàn)utrophin在成熟肌纖維中的表達(dá)上調(diào)可能減少DMD患者肌纖維的損傷。神經(jīng)元型一氧化氮合酶(n NOS)能產(chǎn)生一氧化氮(NO)增加骨骼肌運(yùn)動(dòng)中的血供,且在結(jié)構(gòu)上與dystrophin關(guān)系密切相關(guān),n NOS的異常表達(dá)可能與患者的運(yùn)動(dòng)不耐受癥狀有關(guān)。目前國(guó)內(nèi)外關(guān)于dystrophin、utrophin和n NOS在不同類型肌營(yíng)養(yǎng)不良癥中的表達(dá)研究較少,該研究為明確上述3種蛋白在不同類型肌營(yíng)養(yǎng)不良癥中的表達(dá)情況為肌營(yíng)養(yǎng)不良癥的診斷、分型提供依據(jù),并進(jìn)一步了解3種蛋白表達(dá)與DMD患者病情嚴(yán)重程度的關(guān)系。探索dystrophin、utrophin和n NOS在不同類型肌營(yíng)養(yǎng)不良癥中的表達(dá),進(jìn)一步研究3種蛋白的表達(dá)水平與Duchenne型肌營(yíng)養(yǎng)不良癥(DMD)患者病情嚴(yán)重程度的關(guān)系,及DMD患者中dystrophin、n NOS和utrophin之間的表達(dá)關(guān)系。目的方法1.收集從2013年3月到2015年5月來(lái)我院就診并診斷明確的DMD 26例、BMD7例、肢帶型肌營(yíng)養(yǎng)不良癥(LGMD)10例、面肩肱型肌營(yíng)養(yǎng)不良癥(FSHD)5例、遠(yuǎn)端型肌營(yíng)養(yǎng)不良癥5例和強(qiáng)直性肌營(yíng)養(yǎng)不良癥(DM)11例。收集同時(shí)間段行肌肉活檢病理結(jié)果正常者或急診外傷患者作為對(duì)照組21例。利用免疫熒光方法檢測(cè)3種蛋白在肌營(yíng)養(yǎng)不良癥患者和對(duì)照組中的表達(dá)水平并進(jìn)行熒光強(qiáng)度分級(jí),比較組間蛋白的表達(dá)水平。2.收集DMD患者病情嚴(yán)重程度指標(biāo):Hammersmith功能運(yùn)動(dòng)評(píng)分(HFMS),患者出現(xiàn)下述癥狀時(shí)的年齡:首發(fā)運(yùn)動(dòng)癥狀、上下樓梯困難、不能獨(dú)立行走。根據(jù)dystrophin、n NOS的免疫熒光染色將DMD患者分為2組:完全缺失組和部分缺失組,根據(jù)utrophin的免疫熒光染色分為3組:正常陰性組、輕度增加組和明顯增加組,比較組間患者病情嚴(yán)重程度指標(biāo)的差異。3.用spearman秩相關(guān)分析DMD患者的dystrophin、utrophin和n NOS表達(dá)的相關(guān)性。結(jié)果1 3種蛋白在不同類型肌營(yíng)養(yǎng)不良癥中的表達(dá)與對(duì)照組相比,3種蛋白在LGMD、FSHD、遠(yuǎn)端型肌營(yíng)養(yǎng)不良癥和DM中的表達(dá)差異均無(wú)統(tǒng)計(jì)學(xué)意義;與對(duì)照組和其他類型肌營(yíng)養(yǎng)不良癥相比,DMD和BMD中的dystrophin和n NOS的表達(dá)均減少(P0.002),utrophin的表達(dá)均增多(P0.002),且DMD中dystrophin減少較BMD嚴(yán)重(P0.002)。2 DMD患者中3種蛋白不同表達(dá)水平組間患者病情嚴(yán)重程度的分析Dystrophin和n NOS的2組間患者病情嚴(yán)重程度指標(biāo)的差異均無(wú)統(tǒng)計(jì)學(xué)意義。utrophin的3組間比較:utrophin明顯增加組患者出現(xiàn)上下樓梯困難和不能獨(dú)立時(shí)的年齡較正常陰性組和輕度增加組晚(P0.05),其他組間病情嚴(yán)重程度指標(biāo)比較差異無(wú)統(tǒng)計(jì)學(xué)意義。3 DMD中3種蛋白的相關(guān)性相關(guān)分析結(jié)果:utrophin與dystrophin的表達(dá)呈負(fù)相關(guān)(r=-0.598,P0.05),而n NOS與utrophin、dystrophin均無(wú)相關(guān)性。結(jié)論1.Dystrophin、utrophin和n NOS在DMD和BMD中表達(dá)異常,有助于為DMD和BMD的診斷和分型提供依據(jù)。2.DMD中utrophin的表達(dá)增加能延緩病情進(jìn)展,而dystrophin和n NOS的表達(dá)對(duì)病情無(wú)明確影響。3.DMD患者中utrophin和dystrophin的表達(dá)呈負(fù)相關(guān),提示dystrophin的表達(dá)減少可能反饋性引起utrophin的表達(dá)上調(diào)。
[Abstract]:Research background in the EU, the incidence of muscular dystrophy rate is 1/2000, slow progression, high disability rate, poor prognosis, there is no effective treatment at present, research on disease diagnosis and treatment is very important. Dystrophin (dystrophin) plays an important role in maintaining the structural integrity of muscle fibers. Mutations in the dystrophin gene of Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD). The dystrophin associated protein (utrophin) is dystrophin homologous protein, two protein structures are highly similar, utrophin mainly in regenerating muscle fibers express and maintain the integrity of the muscle fiber structure, almost all replaced by dystrophin in mature muscle fibers, in recent years through animal experiments found that utrophin expression was up-regulated in mature muscle fibers in DMD patients may reduce muscle damage of neuronal oxygen. Nitrogen synthase (n NOS) can produce nitric oxide (NO) increase in skeletal muscle blood supply, and the structure and relationship of dystrophin is closely related to the abnormal expression of n NOS may not exercise tolerance and symptoms. At home and abroad about the expression of dystrophin, utrophin and N less NOS in different type muscular dystrophy in the study, to clarify the 3 proteins in different types of muscular dystrophy in the expression for the diagnosis of muscular dystrophy, provide the basis for the classification, and further understand the 3 protein expression in patients with DMD disease severity. The relationship between the expression of utrophin and N on dystrophin, NOS in different types of muscular dystrophy in the further study of 3 protein expression with Duchenne muscular dystrophy (DMD) relationship between the severity of the disease, and in patients with DMD dystrophin, n NOS and utrophin. The relationship between the expression of objective methods. 1. collection from March 2013 to May 2015 in our hospital and diagnosed 26 DMD cases, BMD7 cases, limb girdle muscular dystrophy (LGMD) in 10 cases, facioscapulohumeral muscular dystrophy (FSHD) in 5 cases, distal muscular dystrophy and 5 cases of ankylosing muscular dystrophy (DM) in 11 cases. Collect the same time muscle biopsy results were normal or emergency trauma patients as the control group. 21 cases were detected by fluorescence intensity grading immunofluorescence method of 3 proteins in muscular dystrophy patients and the control group in the expression level and compared between groups, protein the expression level of.2. in patients with DMD severity index: Hammersmith motor function score (HFMS), patients have the following symptoms: the age of starting motor symptoms, stairs difficult, unable to walk independently. According to dystrophin, N and NOS immunofluorescence staining in DMD patients 2 group: complete deletion group and partial deletion group according to immunofluorescence staining for utrophin were divided into 3 groups: normal group and negative group, a slight increase in.3. increased group, differences were compared between patients with the severity of the disease index by Spearman rank correlation analysis with DMD dystrophin, n NOS and the correlation between the expression of utrophin. Results 13 kinds of protein in different types of muscular dystrophy in expression compared with the control group, 3 proteins in LGMD, FSHD, differential expression of distal muscular dystrophy and DM were not statistically significant; compared with the control group and other types of muscular dystrophy, the expression of DMD and BMD in dystrophin n and NOS were decreased (P0.002), the expression of utrophin was increased (P0.002), and DMD dystrophin BMD (P0.002) is a serious reduction in expression level between the groups with the severity of Dystrophin and N NOS analysis of 3 different kinds of protein.2 in patients with DMD 2 The difference between the 3 groups was the severity of the disease index were not statistically significant.Utrophin utrophin significantly increased in patients receiving the stairs difficult and can not be independent of age than normal group and negative group increased slightly later (P0.05), the other group of 3 protein disease severity index had no difference the significance of.3 DMD in the correlation analysis results: the expression of utrophin was negatively correlated with dystrophin (r=-0.598, P0.05), n NOS and utrophin dystrophin were not correlated. Conclusion 1.Dystrophin, abnormal expression of utrophin and N NOS in DMD and BMD, helps to provide the basis for the expression of.2.DMD in the increase of utrophin can delay the disease progress for the diagnosis of DMD and BMD and the type, and the expression of dystrophin and N NOS on the condition of no clear effect on the expression of utrophin was negatively related to dystrophin and.3.DMD patients, suggesting that the expression of dystrophin decreased Less likely feedback caused the up-regulated expression of utrophin.

【學(xué)位授予單位】：鄭州大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2016
【分類號(hào)】：R746.2

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