中樞神經(jīng)系統(tǒng)炎性脫髓鞘病的動(dòng)物模型實(shí)驗(yàn)和臨床研究
本文選題:多發(fā)性硬化 + 實(shí)驗(yàn)性自身免疫性腦脊髓炎 ; 參考:《第二軍醫(yī)大學(xué)》2007年碩士論文
【摘要】: 研究背景和目的:多發(fā)性硬化(MS)是一種比較常見(jiàn)的中樞神經(jīng)系統(tǒng)炎性脫髓鞘病,臨床表現(xiàn)為病情的反復(fù)復(fù)發(fā)和緩解交替進(jìn)行,其主要的病理特點(diǎn)為不同程度炎細(xì)胞浸潤(rùn)、髓鞘脫失及星型膠質(zhì)細(xì)胞增生,而軸索相對(duì)保留。實(shí)驗(yàn)性自身免疫性腦脊髓炎(EAE)被公認(rèn)為是MS的理想動(dòng)物模型,具有與MS類似的病理改變,是目前研究MS的主要?jiǎng)游锬P。近年隨著病理學(xué)技術(shù)的不斷進(jìn)步,研究發(fā)現(xiàn)在MS和EAE模型伴有軸索損傷,且臨床不可逆的神經(jīng)功能障礙就和軸索損傷相關(guān)。本實(shí)驗(yàn)通過(guò)建立EAE動(dòng)物模型,用病理學(xué)技術(shù)的方法在其發(fā)病早期對(duì)軸索損傷進(jìn)行病理研究。 研究方法:選用髓鞘蛋白脂蛋白(PLP139-151)多肽作為抗原,聯(lián)合不完全福氏佐劑、卡介苗免疫較敏感的雌性SJL/J小鼠,同時(shí)尾靜脈注射百日咳桿菌,誘發(fā)EAE小鼠模型。每日進(jìn)行神經(jīng)功能評(píng)分及稱重,待發(fā)病后剝離腦及脊髓組織,標(biāo)本連續(xù)切片,進(jìn)行HE染色、LFB染色、Bodian銀染及抗淀粉樣前體蛋白(APP)抗體標(biāo)記軸索、抗髓鞘堿性蛋白(MBP)抗體標(biāo)記髓鞘、抗膠質(zhì)纖維酸性蛋白(GFAP)抗體標(biāo)記星型膠質(zhì)細(xì)胞的免疫組織化學(xué)檢查,并進(jìn)行鏡下觀察比較。 結(jié)果:7只(23.3%)小鼠在免疫后的15~22天內(nèi)達(dá)到臨床評(píng)分1分以上,平均發(fā)病時(shí)間為19±2.58天,平均神經(jīng)功能評(píng)分為2.14±0.69分。免疫前小鼠平均體重為21.85±0.94g,發(fā)病后體重為23.24±1.55g(無(wú)顯著統(tǒng)計(jì)學(xué)差異)。HE染色可見(jiàn)發(fā)病小鼠軟腦膜下大腦皮質(zhì)和軟脊膜下脊髓組織可見(jiàn)明顯的炎性細(xì)胞浸潤(rùn),以小血管周圍為主的血管袖套形成。病變累及脊髓多見(jiàn),且比大腦病變重。LFB染色可見(jiàn)炎細(xì)胞浸潤(rùn)處髓鞘有不同程度的脫失,同時(shí)Bodian銀染可見(jiàn)軸索腫脹、橫斷。免疫組織化學(xué)染色可見(jiàn)MBP著色的相同區(qū)域APP濃染,而星型膠質(zhì)細(xì)胞增生不明顯。 結(jié)論:PLP多肽誘發(fā)SJL/J小鼠的EAE模型,臨床癥狀較輕,都在Kono評(píng)分3分以下。EAE病變主要累及脊髓,而在大腦未能見(jiàn)到與MS類似的典型的病灶。在EAE發(fā)病早期,髓鞘還未明顯脫失的時(shí)候就可以見(jiàn)到軸索損傷,早期與臨床癥狀并不平行。 研究背景和目的:中樞神經(jīng)系統(tǒng)炎性脫髓鞘病變?cè)谂R床和影像上有時(shí)可以有類似腫瘤的表現(xiàn),而在病理學(xué)上與多發(fā)性硬化等脫髓鞘病變有相似之處,稱之為炎性脫髓鞘假瘤(DPT),也稱為假瘤型炎性脫髓鞘病。其臨床和影像學(xué)診斷均比較困難,常被誤診為腫瘤性病變。本臨床研究總結(jié)分析了我院10余年來(lái)35例DPT的臨床表現(xiàn)、影像及病理特點(diǎn),并與腦膠質(zhì)瘤進(jìn)行鑒別,以期加強(qiáng)對(duì)本病的認(rèn)識(shí),并提高診斷的正確性。 方法:回顧分析35例均為臨床、影像或和病理證實(shí)的脫髓鞘假瘤,其中18例為活檢證實(shí)(2例為脊髓),總結(jié)其臨床、影像及病理特點(diǎn)。 結(jié)果:本組35例患者發(fā)病年齡9~69歲,性別差異不明顯。發(fā)病前多無(wú)明確的前驅(qū)感染史或誘因。病變單純累及大腦病灶多為多發(fā),而脊髓、腦干病灶單發(fā)者多,且癥狀與影像分離,病灶大而多,但癥狀及體征相對(duì)少。病灶CT強(qiáng)化不明顯,而磁共振檢查(MRI)可見(jiàn)環(huán)形、片狀強(qiáng)化,有占位效應(yīng)。9例行彌散加權(quán)象(DWI)均為明顯高信號(hào),有別于腦膠質(zhì)瘤。腦脊液髓鞘堿性蛋白(MBP)檢查對(duì)于鑒別膠質(zhì)瘤有幫助。病理除表現(xiàn)為典型脫髓鞘、炎細(xì)胞浸潤(rùn)及反應(yīng)性星形細(xì)胞增多外,多數(shù)可找見(jiàn)核分裂狀的Creutzfeuldt細(xì)胞(肥胖星形膠質(zhì)細(xì)胞)。治療后病灶縮小或消失,但不能把試驗(yàn)性的激素治療有效作為鑒別DPT和膠質(zhì)瘤的主要依據(jù)。 結(jié)論:DPT是一種酷似腦腫瘤的特殊類型的脫髓鞘病,其臨床表現(xiàn)和常規(guī)影像學(xué)檢查難以與腦腫瘤鑒別,而DWI檢查有助于鑒別,其病理改變除符合脫髓鞘之外,還可見(jiàn)到特征性的Creutzfeuldt細(xì)胞?上仍囉眉に刂委熁蛘呓M織活檢,不要急于手術(shù)切除。
[Abstract]:BACKGROUND & OBJECTIVE : Multiple sclerosis ( MS ) is a common inflammatory demyelinating disease of the central nervous system . The clinical manifestations are repeated recurrence and remission of the disease . The main pathological characteristics are different degrees of inflammatory cell infiltration , myelinating loss and astrocyte hyperplasia , and the relative retention of axons . In recent years , with the continuous progress of pathological technique , it has been found that the MS and the model of the disease are associated with axonal injury .
Methods : The myelin protein lipoprotein ( PLP139 - 151 ) polypeptide was used as antigen , combined with incomplete Fu ' s adjuvant and BCG vaccine to induce the female SJL / J mice .
Results : 7 ( 23 . 3 % ) mice achieved clinical score of 1 or more in 15 - 22 days after immunization . The average onset time was 19 鹵 2.58 days . The average neurological function score was 2.14 鹵 0.69 . The average body weight was 21.85 鹵 0.94 g , and the body weight was 23.24 鹵 1.55g ( no significant difference ) .
Conclusion : The clinical symptoms of SJL / J mice induced SJL / J mice are less than 3 points in the brain , and the typical lesions similar to MS are not seen in the brain . In the early stage of the onset of the disease , the axonal injury can be seen in the early stage of the disease , and the early and clinical symptoms are not parallel .
BACKGROUND & OBJECTIVE : The clinical and imaging diagnosis of inflammatory demyelinating lesions of the central nervous system can sometimes be similar to those of multiple sclerosis , and it is called inflammatory demyelinating pseudotumor . The clinical and imaging findings are difficult and often misdiagnosed as neoplastic lesions . This clinical study summarizes the clinical manifestation , imaging and pathological characteristics of 35 patients with brain glioma in our hospital for more than 10 years , and identifies them with glioma , with a view to enhancing the awareness of the disease and improving the accuracy of diagnosis .
Methods : The clinical , radiological and pathological characteristics of 35 cases of demyelinating pseudotumor confirmed by clinical , imaging or pathology were retrospectively analyzed .
Results : In 35 patients , the age ranged from 9 to 69 years old and the sex difference was not obvious . There was no clear history of preinfection or inducement before the onset of disease .
Conclusion : The clinical manifestation and conventional imaging examination are difficult to distinguish with brain tumors . The clinical manifestation and routine imaging examination are difficult to distinguish with brain tumors , and DWI examination is helpful to differentiate .
【學(xué)位授予單位】:第二軍醫(yī)大學(xué)
【學(xué)位級(jí)別】:碩士
【學(xué)位授予年份】:2007
【分類號(hào)】:R-332;R744
【參考文獻(xiàn)】
相關(guān)期刊論文 前6條
1 郭秀海,吳衛(wèi)平,朱克;假瘤型炎性脫髓鞘病的臨床及病理[J];腦與神經(jīng)疾病雜志;2002年04期
2 馬林,蔡幼銓,高元桂,梁燕,梁麗,桂秋萍;中樞神經(jīng)系統(tǒng)脫髓鞘性假瘤的MRI表現(xiàn)[J];中華放射學(xué)雜志;2002年07期
3 王偉斌,閆中瑞,馮栓林,趙莉;假瘤型炎性脫髓鞘病一例報(bào)告[J];中華神經(jīng)科雜志;2005年10期
4 戚曉昆,蒲傳強(qiáng),朱克,關(guān)明臣,張鳳英,劉潔曉,朱光明,張曙光,昝世明;實(shí)驗(yàn)性變態(tài)反應(yīng)性腦脊髓炎模型病理及組化研究[J];中華神經(jīng)科雜志;1996年02期
5 宋春杰,尹嶺,王魯寧,朱克;髓鞘蛋白脂質(zhì)蛋白多肽_(139-151)誘發(fā)實(shí)驗(yàn)性自身免疫性腦脊髓炎小鼠模型[J];中國(guó)神經(jīng)免疫學(xué)和神經(jīng)病學(xué)雜志;2001年03期
6 張金濤,金香蘭,朱克,邢廣羽,張笑明,萬(wàn)順倫,宋春杰,尹嶺;PLP不同肽段誘導(dǎo)EAE模型的對(duì)比研究[J];中國(guó)神經(jīng)免疫學(xué)和神經(jīng)病學(xué)雜志;2005年02期
,本文編號(hào):1902906
本文鏈接:http://sikaile.net/yixuelunwen/binglixuelunwen/1902906.html