皮质基底节变性患者的蛋白质组研究

目的 探讨皮质基底节变性的分子机制并寻找诊断治疗该疾病的蛋白质标记物.方法 尸检来自解放军总医院死亡24 h内、经病理证实的男性皮质基底节变性患者(4例)脑及无神经系统疾患的正常老年男性(4例)脑组织,额叶、颞叶和纹状体部位取材,应用HE染色、Gallyas-Braak银染色和Tau蛋白免疫组织化学染色观察皮质基底节变性患者的脑组织学改变;额叶部位取材,以固相pH梯度等电聚焦为第一向,SDS-聚丙烯酰胺凝胶电泳(SDS-PAGE)电泳为第二向进行双向电泳,分析电泳图谱后采用MALDI-TOFTOF串联质谱仪进行蛋白质的鉴定.结果 HE染色显示皮质基底节变性患者额叶神经元明显脱失,伴胶质细胞大量增生,Gallyas-Braak和Tau免疫组化染色结果显示纹状体中大量球形团样缠结;与正常老年人脑组织比较,皮质基底节变性患者脑组织9个蛋白表达增加(经鉴定为coflin、尿嘧啶DNA糖苷水解酶、Cu-Zn超氧化物歧化酶、异柠檬酸脱氢酶亚单位、突触结合蛋白Ⅰ、硫氧还蛋白过氧化物酶1、胶质纤维酸性蛋白、P25alpha、Peroxircdoxin 5),5个蛋白表达下降(经鉴定为碳酰还原酶[NADPH]1、铁蛋白H链、肽基脯氨酸顺反异构酶A、血清白蛋白前体、二氢嘧啶酶相关蛋白2),差异有统计学意义(P＜0.05).结论 上述差异蛋白有助于探讨皮质基底节变性的分子机制及其早期诊断和新药开发.

Abstract：

Objective To investigate the molecular mechanism of corticobasal degeneration and search the protein markers ofdiagnoseis and treatment of this disease. Methods The brains of subjects died without clinical or pathological involvement of nervous system (n=4) and brains of patients with corticobasal degeneration (n=4) were obtained at autopsy. Tissues samples were cut from the frontal and temporal lobes, and the striatum. Histological changes of the tissue samples were observed by HE staining, Gallyas-Braak silver staining and Tau protein immunohistochemistry. The samples extracted from the frontal lobe were performed dimensional electrophoresis with immobilized pH gradient (IPG)isoelectric focusing electrophoresis as the first dimension and with vertical sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) as the second dimension; the maps were visualized by Coomassie brilliant blue staining and analyzed with ImageMaster 2D Elite software; the protein profiles were in-gel digested and identified by mass spectrometry (MALDI-TOFTOF). Results Significant neuron loss in the temporal lobe of patients with corticobasal degeneration was noted by HE staining, with mass proliferation of gliocyte in the temporal lobe; sphere-like entanglement in the striatum was noted by Gallyas-Braak silver staining and Tau immunohistochemistry. Fourteen protein spots in the brains of patients with corticobasal degeneration were differentially expressed as compared with those in age-matched nondemented control brains; the expression of 9 proteins (cofilin, uracil DNA glycosylase,Cu-Zn superoxide dismutase, isocitrate dehydrogenase subunit, synaptotagmin Ⅰ, thioredoxin peroxidase 1, glial fibrillary acidic protein, P25 alpha and peroxiredoxin 5) in brains of patients with corticobasal degeneration was up-regulated as compared with that in the normal brain tissue (P＜0.05); the expression of 5 proteins (carbonyl reductase [NADPH] 1, ferritin heavy chain, peptidyl-prolyl cis-trans isomerase A,serum albumin precursor and dihydropyrimidinase-related protein 2) in brains of patients with corticobasal degeneration was down-regulated as compared with that in the normal brain tissues (P＜0.05).Conclusion We get a number of related-proteins of corticobasal degeneration. Some proteins are quite useful in discovering the molecular mechanisms of corticobasal degeneration and may be helpful in the ealry diagnosis and treatment of corticobasal degeneration and in the development of new medicine.     

Pick病3例临床及病理分析

通过分析3例Pick病的临床、脑MRI、SPECT、PET和脑病理资料,发现和Alzheimer病相比,Pick病早期以人格变化、判断力改变较为特异,情感、情绪变化明显,Kiuever-Bucy综合征为特征,非流利性失语和语义性记忆障碍突出,而智能减退及视觉空间定向能力受损相对较晚,脑MRI以颞极萎缩为重,SPECT和PET以额和（或）颞叶低灌流及低代谢为显著。提示应充分认识Pick病的特点,以利于临床早期诊断。     

轻度认知损害诊断及干预

轻度认知损害(mild cognitive impairment,MCI)是目前在痴呆领域里研究的热点,轻度认知损害定义了一种正常老化与痴呆的交替阶段,反映一种有记忆主诉和客观认知损伤证据但又不能诊断为痴呆的临床状况。轻度认知损害这一概念在识别老年人的记忆下降和高痴呆风险的个体以及对其积极实施干预起重要作用。 1.诊断标准:MCI研究领域的焦点问题之一是诊断标准。加拿大CSHA研究使用标准为“有认知损伤而无痴     

牛磺酸对哮喘豚鼠气道炎症疗效的初步观察

目的 :探讨哮喘豚鼠气道内嗜酸粒细胞浸润和牛磺酸的治疗效果。方法 :采用卵蛋白腹腔注射法复制哮喘豚鼠模型 ,分 3组分别给予生理盐水、牛磺酸和地塞米松治疗 ,比较治疗后支气管肺组织嗜酸粒细胞浸润。结果 :3组豚鼠肺实质内嗜酸粒细胞数 (个 /HP)差异无显著性 (P>0 .0 5 ) ,与地塞米松组差异非常显著 (P<0 0 1) ;支气管粘膜下嗜酸粒细胞数 (个 /mm2 )哮喘组与牛磺酸组差异显著 (P <0 .0 5 ) ;支气管肺泡灌洗液中嗜酸粒细胞数哮喘组与牛磺酸组差异显著 (P <0 .0 5 )。结论 :牛磺酸能有效抑制哮喘豚鼠的气道炎症 ,可能对气道重塑起防治作用。     

Deep cerebral venous thrombosis in adults

Ｄｅｅｐｃｅｒｅｂｒａｌｖｅｎｏｕｓｔｈｒｏｍｂｏｓｉｓ (ＤＣＶＴ)ｉｓａｒａｒｅｆｏｒｍｏｆｃｅｒｅｂｒａｌｖａｓｃｕｌａｒｄｉｓｅａｓｅ Ｉｔｍｏｓｔｏｆｔｅｎｏｃｃｕｒｓｉｎｃｈｉｌｄｒｅｎａｎｄｉｎｆａｎｔｓ ＤＣＶＴｄｉａｇｎｏｓｉｓａｎｄｐｒｏｇｎｏｓｉｓｍａｙｏｆｔｅｎｂｅｄｉｆｆｉｃｕｌｔ ＯｕｒｒｅｃｅｎｔｅｘｐｅｒｉｅｎｃｅｈａｓｌｅｄｕｓｔｏｒｅｃｏｇｎｉｚｅｔｈａｔＤＣＶＴｐｒｅｓｅｎｔｓｗｉｔｈａｎａｔｙｐｉｃａｌｓｙｎｄｒｏｍｅａｎｄｔｉｍｅｃｏｕｒｓｅ ,ｃｈａｒａｃｔｅ…     

成人脑深静脉系统血栓形成

目的：探讨脑深静脉系统血栓形成的病因、临床表现及影像特征和在非急性期局部溶栓治疗的效果。方法：回顾性分析了5例经DSA检查确诊为DCVT患的病因、临床表现及影像特征和在非急性期溶栓治疗的结果。结果：患男3人，女2人，年龄22-49岁，病程1-7月，以发烧为诱因2例，原因不明3例，伴有颅内静脉窦4例。经介入放射局部溶栓和全身抗凝治疗后，神经系统症状和体征明显减轻，未见明显副作用。结论：在诊断DCVT上，DSA比MRI要精确和敏感，且对治疗可进行评估；介入放射局部溶栓和全身抗凝治疗不仅在急性期对DCVT是安全、有效，而且在非急性期亦为一种积极治疗措施。     

双侧壳核内侧区出血致记忆力、计算力减退1例报告

报告1例因双侧大脑壳核内侧区出血导致记忆力、计算力减退的特殊病例。患者3年前突发右侧大脑壳核内侧出血致左侧轻瘫,而无学习、记忆障碍;近来又发生脑出血,影像学检查证实出血部位在左侧大脑壳核内侧,本次除右侧上肢轻瘫外,还伴随近事记忆和记数障碍。这两次脑出血都损伤到脑内与学习记忆有关的新区———边缘区,从临床上证实边缘区参与脑的近事记忆和记数功能。     

晚发型Hallervorden-Spatz病(附尸检报告)

本文报告1例经尸检证实的晚发型Hallcrvorden-Spatz病(进行性苍白球变性综合症)。患者临床表现为巴金森综合症,尸检见病损限于苍白球及黑质:神经细胞脱失伴胶质细胞增生,大量含铁色素颗粒沉积及球形体(Spheroid)形成。文章对该病与其他变性病的鉴别诊断进行初步分析。     

从深化临床医学教学改革中探索年轻医师创新能力培养的思路

本文分析了我国目前临床教学中创新能力培养的主要制约因素是:狭窄的知识面、陈旧的教学模式、附和性的医学实践和被动的学习方式,提出临床医学教育应把素质教育放在重要位置,充分体现以全面素质为基础、以能力为本位的教学指导思想,大力营造创新素质教育氛围,培养年轻医师的创新能力、创新思维。并介绍了我院教学改革对年轻医师创新能力培养的具体做法。     

老年男性不宁腿综合征患者认知功能的调查分析

不宁腿综合征(restless leg syndrome,RLS)为一种常见的老年慢性神经系统疾病.多项研究显示,RLS和帕金森病(PD)密切相关~([1-2]).我们于2006年12月至2007年7月对驻京部队干休所的老年男性RLS患者114例进行认知功能的调查,并与非RLS的老年男性患者进行比较,探讨不同程度RLS对老年男性认知功能的影响.