本文選題：多發(fā)性硬化　切入點：神經(jīng)源性膀胱　出處：《鄭州大學(xué)》2017年碩士論文　論文類型：學(xué)位論文

【摘要】：背景和目的多發(fā)性硬化導(dǎo)致的膀胱功能障礙是泌尿系統(tǒng)里面極為復(fù)雜的疾病。多發(fā)性硬化會給中樞神經(jīng)系統(tǒng)帶來多樣的病理變化,與此同時會出現(xiàn)各個系統(tǒng)臨床癥狀。對于泌尿系統(tǒng),由于受損的泌尿系功能相關(guān)的神經(jīng)病變部位以及受損傷程度不同也會導(dǎo)致泌尿系統(tǒng)功能也將出現(xiàn)各種變化,其中膀胱功能障礙主要表現(xiàn)為尿頻、尿急、尿潴留、尿失禁等。目前對于多發(fā)性硬化這個疾病本身的研究較多,而關(guān)于多發(fā)性硬化神經(jīng)源性膀胱研究則較少.治療方法上面也是主要以控制癥狀,改善泌尿系統(tǒng)功能為主,比如間歇導(dǎo)尿、抗膽堿藥物、肉毒素、辣椒素、手術(shù)等等,治療效果并不理想,針對多發(fā)硬化的治療如免疫抑制劑、免疫球蛋白注射、血漿置換以及β-干擾素等效果也不能讓人們完全滿意,因此需要一種新的同時針對多發(fā)性硬化和神經(jīng)源性膀胱的治療方法。近期有研究表明男女性別的差異會造成自身免疫性疾病發(fā)病差別,女性患者多發(fā)性硬化的患者是男性的2倍,女性懷孕后期多發(fā)性硬化發(fā)病率降低到原來的20%,有研究表明雌性激素對多發(fā)性硬化有防止疾病進一步惡化,促進神經(jīng)修復(fù)的作用。另外還有報道證明雌激素受體在膀胱的分布,以及雌激素對女性膀胱結(jié)構(gòu)和功能的影響,提示了雌激素在治療多發(fā)性硬化神經(jīng)源性膀胱的潛在可能。本實驗通過實驗性自身免疫性腦脊髓炎(experimental autoimmune encephalomyelitis,EAE)的動物模型觀察多發(fā)性硬化導(dǎo)致的膀胱功能障礙,并通過給予模型動物適量的雌激素處理,觀察模型動物變化情況,初步驗證雌激素在多發(fā)性硬化中神經(jīng)源性膀胱的可能治療作用。實驗方法1建立EAE小鼠模型:8-13周的C57BL/6雌性小鼠,應(yīng)用200ug mog35-55,與等體積含CFA量為10mg/ml的完全弗氏佐劑混勻,完全乳化成乳劑,皮下兩點注射,于免疫當(dāng)天及免疫后48小時腹腔注射400ng百日咳毒素誘導(dǎo)EAE小鼠模型。自免疫當(dāng)天起,觀察并記錄大鼠體重變化、臨床表現(xiàn)及神經(jīng)功能評分。2分組以及給藥:選取雌性C57BL6小鼠30只,隨機分10只對照組單純給予完全費氏佐劑以及百日咳,10只為EAE模型組,10只為雌激素處理組,即在完成免疫處理后每日給予雌激素(50μmol/L)100μl皮下注射。3標(biāo)本采集:在試驗23天時,將小鼠用10%水合氯醛麻醉后,取出膀胱組織,稱重,放入液氮中保存,然后取多聚甲醛進行全身灌流,取出小鼠脊髓組織用于制作石蠟切片。4相關(guān)指標(biāo)檢測:Luxol fast blue(LFB)染色和蘇木素-伊紅(HE)染色觀察脊髓炎性細胞浸潤及脫髓鞘情況,用Western-Blot檢測膀胱組織中雌激素受體蛋白表達變化情況。結(jié)果1 EAE模型組的小鼠:神經(jīng)功能臨床評分、體重、以及泌尿系統(tǒng)功能變化都具有典型的MS臨床表現(xiàn),HE染色表現(xiàn)出較明顯相關(guān)的炎性細胞浸潤。LFB染色表現(xiàn)出了明顯的脊髓脫髓鞘現(xiàn)象。2在多發(fā)性硬化神經(jīng)源性膀胱小鼠膀胱組織中,相對于對照組小鼠膀胱中雌激素受體明顯降低,給予雌激素治療后,雌激素受體表達略微上調(diào)。3在給予EAE小鼠雌激素治療后,小鼠發(fā)病率降低,癥狀嚴(yán)重程度較未特殊處理的EAE小鼠輕,平均神經(jīng)功能評分降低。結(jié)論1 EAE神經(jīng)系統(tǒng)臨床癥狀的評分與多發(fā)硬化性神經(jīng)源膀胱的癥狀密切相關(guān)。2雌激素以及雌激素受體在多發(fā)硬化性神經(jīng)源膀胱疾病中發(fā)生可能起到重要用。3在對EAE模型小鼠進行雌激素處理后,發(fā)病率以及癥狀嚴(yán)重程度相對于未經(jīng)雌激素處理的模型組明顯降低,表明雌激素對多發(fā)性硬化導(dǎo)致神經(jīng)源性膀胱有明顯的改善作用。
[Abstract]:Background and objective: multiple sclerosis induced bladder dysfunction is the urinary system which is extremely complicated diseases. Multiple sclerosis will bring various pathological changes to the central nervous system, at the same time the system will appear in various clinical symptoms. For the urinary system, urinary system dysfunction due to the related nerve lesion and damage degree will also cause urinary tract function will also appear various changes, including bladder dysfunction mainly for frequent micturition, urgency of urination, urinary retention, urinary incontinence and so on. At present there are many studies on multiple sclerosis of the disease itself, and on multiple sclerosis of neurogenic bladder research is limited. It is mainly for the treatment of the above control the symptoms, improve the function of urinary system, such as intermittent catheterization, anticholinergic drugs, botulinum toxin, capsaicin, surgery and so on, the treatment effect is not ideal, for many Hardening treatments such as immunosuppressants, immunoglobulin, plasma exchange and beta interferon effect cannot make people completely satisfied, so a new method of treatment for multiple sclerosis and neurogenic bladder. Recent studies have shown that gender differences will cause different incidence of autoimmune diseases women, in patients with multiple sclerosis patients is 2 times that of men, women in late pregnancy incidence of multiple sclerosis is reduced to 20% of the original, studies have shown that estrogen can prevent further deterioration of the disease, multiple sclerosis, promote nerve repair. There are also reported that estrogen receptor in bladder distribution, influence and estrogen on female bladder structure and function, the potential of estrogen in the treatment of multiple sclerosis of neurogenic bladder. Through this experiment, experimental autoimmune Encephalomyelitis (experimental autoimmune, encephalomyelitis, EAE) of the animal model to observe multiple sclerosis caused by bladder dysfunction, and estrogen treated animal model to observe the changes of the amount, animal model, preliminary verification of the possible therapeutic effect of estrogen on multiple sclerosis in neurogenic bladder. 1 experimental methods to establish EAE mice model: C57BL/6 female mice for 8-13 weeks, 200ug MOG35-55, and the volume of CFA content for complete Freund's adjuvant 10mg/ml mix, completely emulsion, subcutaneous injection points, in a mouse model of EAE 48 hours 400ng intraperitoneal injection of pertussis toxin induced immunity after immunization. Immunization day and since that day, observe and record the changes of body weight of rats, the function of clinical manifestations and neurological assessment.2 grouping and administration: 30 female C57BL6 mice were selected and randomly divided into 10 control group received only completely Fisheri Adjuvant and pertussis, 10 for EAE group, 10 for the estrogen treatment group, in complete immunization after treatment given daily doses of estrogen (50 mol/L) 100 L subcutaneous injection of.3 in the test specimen collection: 23 days, mice were anaesthetized with 10% chloral hydrate after removal of bladder tissue, weighing, preservation in liquid nitrogen, and then take the paraformaldehyde systemic perfusion, remove the mouse spinal cord tissue for the production of related indexes of paraffin section and.4 fast blue (LFB): Luxol staining and hematoxylin eosin (HE) staining of spinal cord inflammatory cell infiltration and demyelination situation, with the expression of estrogen receptor protein to detect the change of bladder Western-Blot. Results: 1 EAE mice model group clinical nerve function score, body weight, and urinary system function MS has typical clinical manifestations, HE staining showed obvious correlation of inflammatory cell infiltration showed.LFB staining An obvious demyelination of spinal.2 in multiple sclerosis of neurogenic bladder and bladder tissue in mice, compared with estrogen receptor mice significantly decreased in bladder control, estrogen treatment, estrogen receptor expression slightly upregulated the expression of.3 on EAE mice were given estrogen after treatment, mice reduced the incidence, severity of symptoms is not special EAE mice treated by light, the average neurological function score decreased. Conclusion 1 EAE neurological clinical symptoms score and multiple sclerosis of neurogenic bladder symptoms of.2 is closely related to estrogen and estrogen receptor in multiple sclerosis of neurogenic bladder diseases may play an important.3 in estrogen treatment on EAE model mice, the incidence and severity of symptoms compared with the untreated model group, estrogen treatment significantly decreased, suggesting that estrogen causes neurogenic bladder in multiple sclerosis Cysteine has an obvious improvement.

【學(xué)位授予單位】：鄭州大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R744.51;R694.5

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