中枢神经系统炎性脱髓鞘病的动物模型实验和临床研究

发布时间：2018-05-17 21:19

本文选题：多发性硬化 + 实验性自身免疫性脑脊髓炎　；参考：《第二军医大学》2007年硕士论文

【摘要】： 研究背景和目的:多发性硬化(MS)是一种比较常见的中枢神经系统炎性脱髓鞘病,临床表现为病情的反复复发和缓解交替进行,其主要的病理特点为不同程度炎细胞浸润、髓鞘脱失及星型胶质细胞增生,而轴索相对保留。实验性自身免疫性脑脊髓炎(EAE)被公认为是MS的理想动物模型,具有与MS类似的病理改变,是目前研究MS的主要动物模型。近年随着病理学技术的不断进步,研究发现在MS和EAE模型伴有轴索损伤,且临床不可逆的神经功能障碍就和轴索损伤相关。本实验通过建立EAE动物模型,用病理学技术的方法在其发病早期对轴索损伤进行病理研究。研究方法:选用髓鞘蛋白脂蛋白(PLP139-151)多肽作为抗原,联合不完全福氏佐剂、卡介苗免疫较敏感的雌性SJL/J小鼠,同时尾静脉注射百日咳杆菌,诱发EAE小鼠模型。每日进行神经功能评分及称重,待发病后剥离脑及脊髓组织,标本连续切片,进行HE染色、LFB染色、Bodian银染及抗淀粉样前体蛋白(APP)抗体标记轴索、抗髓鞘碱性蛋白(MBP)抗体标记髓鞘、抗胶质纤维酸性蛋白(GFAP)抗体标记星型胶质细胞的免疫组织化学检查,并进行镜下观察比较。结果:7只(23.3%)小鼠在免疫后的15～22天内达到临床评分1分以上,平均发病时间为19±2.58天,平均神经功能评分为2.14±0.69分。免疫前小鼠平均体重为21.85±0.94g,发病后体重为23.24±1.55g(无显著统计学差异)。HE染色可见发病小鼠软脑膜下大脑皮质和软脊膜下脊髓组织可见明显的炎性细胞浸润,以小血管周围为主的血管袖套形成。病变累及脊髓多见,且比大脑病变重。LFB染色可见炎细胞浸润处髓鞘有不同程度的脱失,同时Bodian银染可见轴索肿胀、横断。免疫组织化学染色可见MBP着色的相同区域APP浓染,而星型胶质细胞增生不明显。结论:PLP多肽诱发SJL/J小鼠的EAE模型,临床症状较轻,都在Kono评分3分以下。EAE病变主要累及脊髓,而在大脑未能见到与MS类似的典型的病灶。在EAE发病早期,髓鞘还未明显脱失的时候就可以见到轴索损伤,早期与临床症状并不平行。研究背景和目的:中枢神经系统炎性脱髓鞘病变在临床和影像上有时可以有类似肿瘤的表现,而在病理学上与多发性硬化等脱髓鞘病变有相似之处,称之为炎性脱髓鞘假瘤(DPT),也称为假瘤型炎性脱髓鞘病。其临床和影像学诊断均比较困难,常被误诊为肿瘤性病变。本临床研究总结分析了我院10余年来35例DPT的临床表现、影像及病理特点,并与脑胶质瘤进行鉴别,以期加强对本病的认识,并提高诊断的正确性。方法:回顾分析35例均为临床、影像或和病理证实的脱髓鞘假瘤,其中18例为活检证实(2例为脊髓),总结其临床、影像及病理特点。结果:本组35例患者发病年龄9~69岁,性别差异不明显。发病前多无明确的前驱感染史或诱因。病变单纯累及大脑病灶多为多发,而脊髓、脑干病灶单发者多,且症状与影像分离,病灶大而多,但症状及体征相对少。病灶CT强化不明显,而磁共振检查(MRI)可见环形、片状强化,有占位效应。9例行弥散加权象(DWI)均为明显高信号,有别于脑胶质瘤。脑脊液髓鞘碱性蛋白(MBP)检查对于鉴别胶质瘤有帮助。病理除表现为典型脱髓鞘、炎细胞浸润及反应性星形细胞增多外,多数可找见核分裂状的Creutzfeuldt细胞(肥胖星形胶质细胞)。治疗后病灶缩小或消失,但不能把试验性的激素治疗有效作为鉴别DPT和胶质瘤的主要依据。结论:DPT是一种酷似脑肿瘤的特殊类型的脱髓鞘病,其临床表现和常规影像学检查难以与脑肿瘤鉴别,而DWI检查有助于鉴别,其病理改变除符合脱髓鞘之外,还可见到特征性的Creutzfeuldt细胞。可先试用激素治疗或者组织活检,不要急于手术切除。
[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 卤 2.58 days . The average neurological function score was 2.14 卤 0.69 . The average body weight was 21.85 卤 0.94 g , and the body weight was 23.24 卤 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 .
【学位授予单位】：第二军医大学
【学位级别】：硕士
【学位授予年份】：2007
【分类号】：R-332;R744

【参考文献】