雷公藤内酯醇对EAE大鼠中枢神经系统炎症浸润细胞凋亡及Bcl-2、Bax的影响

目的 观察雷公藤内酯醇(Tri)对实验性自身免疫性脑脊髓炎(EAE)大鼠中枢神经系统炎症浸润细胞凋亡及凋亡相关蛋白Bcl-2、Bax的影响. 方法 采用四肢足掌皮内注射完全福氏佐剂一豚鼠全脊髓匀浆(CFA-GPSCH),并辅以注射百日咳疫苗,诱导大鼠建立EAE模型.将大鼠随机分为模型组(EAE组)和腹腔注射Tri治疗组(Tri组),免疫后第11天Tri组腹腔注射Tri 40μg/(kg·d),EAE组给予等体积的生理盐水腹腔注射,第17天处死,观察中枢神经系统炎症细胞浸润程度,TUNEL法检测浸润细胞凋亡情况,免疫组化检测浸润细胞Bcl-2、Bax蛋白的表达. 结果 Tri组与EAE组相比,其中枢神经系统炎症浸润细胞的数目减少,凋亡率增高,Bcl-2表达下降,Bax的表达无明显变化,Bcl-2/Bax的比值下降. 结论 Tri可能是通过抑制EAE大鼠中枢神经系统血管周围炎症浸润细胞Bcl-2的表达,降低Bcl-2/bax的比值,从而提高炎症浸润细胞的凋亡率,减少炎症浸润细胞数目,减轻EAE的病情.     

雷公藤内酯醇对实验性自身免疫性脑脊髓炎大鼠行为和MMP-9表达的影响

目的:观察雷公藤内酯醇(Tri)对实验性自身免疫性脑脊髓炎(EAE)大鼠中枢神经系统(CNS)中MMP-9表达的影响。方法:建立雌性EAE大鼠模型,将大鼠随机分为4组:治疗组(EAE Tri组);阳性对照组(EAE NS组);正常对照组(CFA Tri组、CFA NS组),观察Tri对EAE大鼠发病情况的影响,并通过免疫组化法观察Tri对EAE大鼠CNS中MMP-9表达的影响。结果:与EAE NS组比较,EAE Tri组的发病率明显降低,临床评分的平均值和最高值均降低,大鼠脑脊髓白质内炎性细胞浸润和病灶数比EAE NS组明显减少。免疫组化:EAE Tri组大鼠CNS中的MMP-9表达比EAE NS组明显减低。正常对照组大鼠均未发病,CNS中也无炎性细胞浸润及MMP-9表达。结论:Tri能抑制EAE大鼠CNS中MMP-9的表达,减轻EAE大鼠临床症状、降低发病率。     

实验性自身免疫性脑脊髓炎大鼠血CD4+CD25+T细胞的研究

目的探讨实验性自身免疫性脑脊髓炎(EAE)动物模型血CD4 CD25 T细胞的变化及其意义。方法以豚鼠全脊髓匀浆(GPSCH)为抗原免疫Wistar大鼠,建立EAE的动物模型,采用三色流式细胞仪检测EAE和正常大鼠外周血CD4 CD25 T细胞的细胞数并进行比较;通过观察大鼠行为学及脑和脊髓的病理改变确定EAE。结果EAE模型大鼠的成功率为48.9%,EAE大鼠外周血CD4 CD25 T淋巴细胞数(5.29±4.00)显著低于正常对照组(12.61±2.24)(P<0.01)。结论EAE大鼠血CD4 CD25 T细胞数明显减少,CD4 CD25 T淋巴细胞对神经系统脱髓鞘疾病是一种保护因子。     

外源性雄激素对EAE大鼠血中CD4+CD25+T细胞的影响

目的 探讨外源性雄激素对实验性自身免疫性脑脊髓炎(experimental allergic eneephalomyelitis, EAE)大鼠外周血CD4 CD25 T的影响.方法 模型组用豚鼠脊髓和完全弗式佐剂混匀乳剂诱发大鼠EAE,治疗组在模型组的基础上给予外源性雄激素,观察各组的发病情况;流式细胞仪检测外周血CD4 CD25 T细胞;HE染色和髓鞘染色分别观察病理和髓鞘改变.结果 治疗组的CD4 CD25 T细胞(5.3±0.90)较模型组(6.5±0.90)显著增高(P＜0.01),大脑、脑干、脊髓炎性细胞浸润明显减少,髓鞘的改变不明显.结论 外源性雄激素可能通过改变了CD4 CD25 T细胞的水平,而对EAE起一定的治疗作用.     

神经胶质瘤患者外周血淋巴细胞亚群检测的临床分析

目的：分析神经胶质瘤患者检测其外周血淋巴细胞亚群的临床意义。方法选择2011-12-2013-08在我院接受诊治的神经胶质瘤患者65例作为观察组,选择同期在我院健康体检者43例作为对照组。分析2组患者采用流式细胞术检测CD3＋CD4＋、CD3＋CD8＋、CD4＋/CD8＋、CD3＋ T淋巴细胞及CD4＋CD25＋ T reg水平。结果观察组外周血中CD3＋ CD4＋T细胞与CD4＋/CD8＋比值较对照组显著降低（ P＜0.05）;A组外周血中CD3＋CD4＋百分比、CD4＋/CD8＋比值均较B组显著降低（ P＜0.05）;A组外周血中CD3＋CD8＋百分比较B组显著升高（ P＜0.05）;观察组CD4＋ CD25＋ T reg百分比较对照组显著升高（P＜0.05）;A组CD4＋CD25＋ Treg百分比较B组显著升高（P＜0.05）。结论恶性肿瘤存在免疫功能紊乱,对于神经胶质瘤外周血淋巴细胞的检测,尤其T reg细胞,有利于对神经胶质瘤患者恶性程度及疗效进行判断。     

多发性硬化患者外周血肿瘤坏死因子超家族成员LIGHT及其受体HVEM的表达

目的 为分析TNF家族成员LIGHT及其受体疱疹病毒侵入介体（herpesvirus entry mediator，HVEM）与多发性硬化（MS）的关系，尝试性地研究了MS患者外周血T细胞LIGHT和HVEM的表达。方法 用流式细胞仪检测了LIGHT和HVEM在未治疗MS、免疫抑制治疗MS、脑卒中患者以及正常对照组外周血CD4^＋、CD8^＋T细胞的表达。结果 与正常对照比较．免疫调节治疗MS患者表达HVEM的外周血单个核细胞（PBMC）、CD4^＋和CD8^＋T细胞明显增多（分别为P〈0．001、P〈0．01和P〈0．001）。LIGHT尽管在未治疗MS组CD8^＋T细胞的表达呈增高趋势．但各组间差异无显著性。结论 LIGHT上调可能与CD8^＋T细胞的表达相关，LIGHT和HVEM之间是否存在调节性反馈环路尚需探讨。     

实验性自身免疫性神经炎相关细胞的免疫机制

目的 建立P2或P0多肽诱导的实验性自身免疫性神经炎（EAN）大鼠模型，确定诱导EAN的优选抗原和剂量，探讨EAN相关细胞免疫机制。方法 实验组用P2 57-81或P0 180-190多肽加完全弗氏佐剂（FCA）免疫Lewis大鼠，对照组单用FCA免疫，致敏后每日对大鼠进行临床评分，比较高峰期最大评分，致敏第14天进行淋巴细胞增殖试验，测定CD4^＋T／淋巴结单个核细胞（MNC）和CD4^＋CD25^＋T／CD4^＋T细胞百分比，并进行坐骨神经病理检查。结果实验大鼠瘫痪高峰期最大评分，P2 57-81200μg组显著高于P2 57-81 100μg组和P0 180-199 200μg组（均P〈0．01），P2 57-81 100μg组与P0 180-199 200μg组差异无统计学意义；P2 57-81 100μg组和P2 57-81 200μg组对P2 27-81多肽刺激反应性显著高于对照组（均P〈0．01），P0 180-199 200μg组对P0 180-199多肽刺激反应性显著高于对照组（P〈0．01），P2 57-81 100μg组和P0 180-199 200μg组对相应致敏多肽刺激反应性显著低于P2 57-81 200μg组（均P〈0．05）；CD4^＋T／淋巴结MNC百分比在各组间差异无统计学意义；CD4^＋CD25^＋T／CD4^＋T细胞百分比，P2 57-81 200μg组显著低于P2 57-81 100μg组、P0 180-199 200μg组和对照组（均P〈0．01），P2 57-81 100μg组和P0 2180-199 200μg组显著低于对照组（均P〈0．01），P0 180-199 200μg组显著低于P2 57-81 100μg组（P〈0．01）；EAN急性期坐骨神经以炎性细胞浸润为主，P257-81 200μg组重于其他实验组（均P〈0．01），P257-81 200μg组慢性期无炎性细胞浸润，而表现多发性局灶性脱髓鞘和神经纤维崩解未恢复。结论 200μgP257-81多肽是诱导EAN的优选抗原，EAN致病与CD4^＋T细胞数量无关，而与致病性T细胞活性增强及CD4^＋CD25^＋T细胞减少有关。     

盐酸法舒地尔治疗实验性自身免疫性脑脊髓炎的潜能与抗炎作用

目的：探讨盐酸法舒地尔对实验性自身免疫性脑脊髓炎（EAE）的治疗效果及机制。方法：雌性C57BL/6小鼠,随机分为EAE对照组、盐酸法舒地尔干预组和盐酸法舒地尔治疗组。采用髓鞘少突胶质细胞糖蛋白多肽诱导慢性EAE模型。干预和治疗分别在免疫后第3天和症状出现时予以腹腔注射盐酸法舒地尔,观察EAE模型小鼠体重变化和临床症状,进行苏木精-伊红和CD4＋T细胞染色,同时检测磷酸化肌球蛋白磷酸酶（p-MYPT1）和核因子（NF-κB）。结果：盐酸法舒地尔可推迟并改善EAE小鼠症状,减轻中枢神经系统炎细胞浸润,抑制脊髓和脑p-MYPT1及脊髓NF-κB的表达。     

黏附分子CD44在实验性自身免疫性脑脊髓炎中的作用

目的 探讨黏附分子CD44在实验性自身免疫性脑脊髓炎（EAE）发病中的作用。方法 将20只大鼠随机分为正常对照组及EAE组,EAE组采用粗制髓鞘碱性蛋白（MBP）抗原注入大鼠后足掌皮下（0.2 ml/100 g）制作EAE模型,观察大鼠的发病情况及病理表现;并采用免疫组织化学法检测两组大鼠脑组织CD44的含量。结果 正常对照组大鼠未发病,EAE组大鼠均有不同程度的发病。HE染色后,光镜下观察,正常对照组大鼠脑和脊髓无异常;EAE组大鼠可见脑及脊髓实质内小血管充血,小静脉周围有大量炎性细胞浸润,血管周围白质脱髓鞘改变。免疫组化显示,正常对照组大鼠脑和脊髓组织未发现CD44阳性细胞;EAE组大鼠中枢神经系统（CNS）白质及灰白质交界处可见大量CD44阳性细胞。结论 EAE模型中存在黏附分子CD44的高表达,其对EAE的发病可能起到促进作用。     

脑胶质瘤免疫治疗的实验研究

目的：提纯大鼠脑胶质瘤C6细胞热休克蛋白抗原肽复合物（HAC），免疫大鼠，观察HAC的抑瘤作用。方法：彩免疫亲和层析方法提纯鼠脑胶质瘤C6细胞HAC，免疫20只大鼠为实验组，以另20只大鼠作为对照组，于免疫后1周，采用立体定向脑内接种方法，以C6细胞攻击两组大鼠，于肿瘤细胞攻击后第2周，取两组动物外周静脉血，并采20只正常动物的外周静脉血做为正常对照，测定外周静脉血淋巴细胞计数。观察饲养过程中实验动物出现的症状、体征和第四周实验动物存尖率。于第四周处死存活动物，取脑组织进行HE染色病理组织学检查，并用免疫组化方法分析脑胶质瘤浸润区T淋巴细胞分布情况。结果：实验组大鼠外周血淋巴细胞计数显高于对照组（P＜0．01）。实验组胶质瘤局部浸润的CD3＋和CD4＋细胞数均显高于对照组（P＜0．01），实验组胶质瘤局部浸润的CD8＋细胞数与对照组比较无显性差异（P＞0．05），实验组胶质瘤局部浸润T淋巴细胞CD4＋／CD8＋显高于对照组（P＜0．01）。实验组动物症状出现时间显晚于对照组动物（P＜0．05），实验组动物四周末存活率显高于对照组（P＜0．01）。结论：C6细胞中HAC可以诱导大鼠产生对C6细胞的细胞免疫，提高大鼠存活率。     

Denervation study of synapses of organ of corti of old world monkeys

Fine structural characteristics of synapses in the spiral organ of Corti were examined, with reference to differences between inner and outer haircell systems, and to location of neurons of origin of efferent axons. Surgical interruption of crossed olivocochlear bundle, of vestibular nerve, of facial nerve, and excision of superior cervical ganglia were used to determine the pathways of efferent axons. Interruption of the vestibular nerve near the brainstem results in degeneration of all efferent terminals on outer hair cells. Mid-line lesions at, and caudal to, the facial colliculus result in degeneration of about half of these efferent terminals. Efferent synaptic bulbs to the inner hair-cell system are small, of the order of one micron, and form type 2 junctions with afferent dendrites. They tend to have more large dense-core vesicles (about 80 nm) than the large efferent terminals of the outer hair-cell system, and appear to be the terminals of axons in the habenula perforata, which exhibit varicosities laden with large dense core vesicles. The varicosities are unaffected by excision of the superior cervical ganglia. So far as our material can reveal, it appears that the varicosities in the habenula perforata do not survive vestibular root interruption, nor do the efferent processes in the internal spiral bundle or at the base of inner hair cells. Most interestingly, the afferent processes of the inner hair-cell system, as identified for example by their relation to pre-synaptic bodies in the inner hair cells, are subject to a trans-synaptic reaction after severance of the vestibular root. They undergo a dramatic cytological transformation, characterized by increase of volume, engorgement with microtubules, microfilaments, microvesicles of various sizes, and clusters of lysosomes. Thus, both the efferent and afferent terminals of the inner hair-cell system show marked cytological differences from the corresponding terminals of the outer hair cell system.     

Mechanism of action of tubocurarine on nicotinic cholinoreceptors of neurons of the sympathetic ganglia of rats

Tubocurarine (Tc) effect on membrane currents elicited by acetylcholine (ACh) was studied in isolated superior cervical ganglion neurons of rat using patch-clamp method in the whole-cell recording mode. The "use-dependent" block of ACh current by Tc was revealed in the experiments with ACh applications, indicating that Tc blocked the channels opened by ACh. Mean lifetime of Tc-open channel complex, tau, was found to be 9.8 +/- 0.5 s (n = 7) at -50 mV and 20-24 degrees C. tau exponentially increased with membrane hyperpolarization (e-fold change in tau corresponded to the membrane potential shift by 61 mV). Inhibition of the ACh-induced current by Tc (3-30 microM/1) was completely abolished by membrane depolarization to the level of 80-100 mV. Inhibition of ACh-induced current was augmented at increased ACh doses. It is concluded that the open channel block produced by Tc is likely to be the only mechanism for Tc action on nicotinic acetylcholine receptors in superior cervical ganglion neurons of rat.     

The effect of age of onset of PD on risk of dementia

Background Dementia occurs in the majority of patients with Parkinson’s disease (PD). Late onset of PD has been reported to be associated with a higher risk for dementia. However, age at onset (AAO) and age at baseline assessment are often correlated. The aim of this study was to explore whether AAO of PD symptoms is a risk factor for dementia independent of the general effect of age. Methods Two community-based studies of PD in New York (n = 281) and Rogaland county, Norway (n = 227) and two population-based groups of healthy elderly from New York (n = 180) and Odense, Denmark (n = 2414) were followed prospectively for 3–4 years and assessed for dementia according to DSM-IIIR. All PD and control cases underwent neurological examination and were followed with neurological and neuropsychological assessments. We used Cox proportional hazards regression based on three different time scales to explore the effect of AAO of PD on risk of dementia, adjusting for age at baseline and other demographic and clinical variables. Findings In both PD groups and in the pooled analyses, there was a significant effect of age at baseline assessment on the time to develop dementia, but there was no effect of AAO independent of age itself. Consistent with these results, there was no increased relative effect of age on the time to develop dementia in PD cases compared with controls. Interpretation This study shows that it is the general effect of age, rather than AAO that is associated with incident dementia in subjects with PD. Received in revised form: 22 December 2005     

Limits of deinstitutionalization--perspectives of relatives of psychiatric patients

After a hopeful beginning, the social process of the reintegration of those with severe mental illness has come to a standstill. I am led to wonder whether "the community" really wants to live together with people suffering from severe mental illness, and if so, how closely? As long as the medical treatment of mental illness provided by the general practitioners is fundamentally deficient, as they are not able to prescribe the necessary interventions--such as out-patient psychiatric nursing, and service providers in the out-patient sector are content with offering increasingly intensive forms of care for the less seriously ill at the cost of the Social Welfare System--the reintegration of those with serious mental illness remains an illusion--which is mainly to the benefit of providers of residential care in homes and hostels.     

Sense of coherence as a predictor of subjective state of health: results of 4 years of follow-up of adults

A number of cross-sectional population studies have shown that a strong sense of coherence (SOC) is associated with various aspects of good perceived health. The association does not seem to be entirely attributable to underlying associations of SOC with other variables, such as age or level of education. OBJECTIVE: The aim of the study reported here was to determine whether SOC predicted subjective state of health. METHODS: The study was carried out as a two-way panel mail survey of 1976 individuals with 4 years interval for two collections of data. The statistical method used was multivariate cumulative logistic modeling. Age, initial subjective state of health, initial occupational training level, and initial degree of social integration were included as potential explanatory variables. RESULTS: A strong SOC predicted good health in women and men. CONCLUSIONS: SOC can be interpreted as an autonomous internal resource contributing to a favorable development of subjective state of health. SOC data should, however, be regarded as complementary to and not a substitute for information already known to be associated with increased risk of future ill health.