CD28/B7-1在多发性肌炎中的作用及雷公藤多甙的影响

多发性肌炎 (ｐｏｌｙｍｙｏｓｉｔｉｓ,ＰＭ)是一组常见的自身免疫性炎性肌病。已有研究表明 ,ＰＭ的发病机制与Ｔ细胞异常活化有关。Ｔ细胞的活化需要两个刺激信号 :Ｔ细胞受体 /白细胞分化抗原 3(ＴＣＲ/ＣＤ3)复合物与抗原提呈细胞 (ＡＰＣ)上的组织相容性抗原 Ⅱ (ＭＨＣ Ⅱ )类抗原结合 ,提供第一信号 ;Ｔ细胞上的协同刺激分子如ＣＤ2 8与ＡＰＣ表面的配体 (Ｂ7 1 /Ｂ7 2 )结合提供第二信号 ,在第二信号的协同作用下 ,Ｔ细胞活化 ,增殖分化为效应细胞。阻断或抑制Ｔ细胞的活化过程 ,使其处于无反应状态 ,则有可能达到治疗ＰＭ的目的。…     

自身免疫性多发性肌炎

多发性肌炎(PM)是指肌肉广泛炎性病变,临床主要表现为肌无力等症状的一类肌肉疾病,病因未明,可能与感染、中毒、恶性肿瘤、胶原病和药物等有关。本文综述一组与自身免疫有关的PM,称为自身免疫性多发性肌炎(AIPM)。     

实验性肌炎动物模型的肌酶研究

目的 研究实验性肌炎动物模型的肌酶改变。方法 本文参照Dawkin方法用家兔骨骼肌匀浆多次免疫豚鼠制作成实验性肌炎模型,动态观察其肌酶(CK、LDH、AST)变化。结果 实验性肌炎动物模型肌酶与对照组比较显著升高,其中以CK最为敏感。且与病理改变相平行。这与人类多发性肌炎(PM)相类似。结论 表明肌酶可作为模型建立的指标,亦可为判断其病变程度的指标。     

实验性肌炎动物模型制作的研究

目的 研究制作实验性肌炎动物模型的方法。方法 利用家兔骨骼肌匀浆加佛氏佐剂多次免疫豚鼠制成实验性肌炎模型,观察其在肌酶、肌电图（ＥＭＧ）、病理的改变。并与人类多发性肌炎（ＰＭ）作比较。结果 发现其与人类多发性肌炎（ＰＭ）在肌酶、肌电图（ＥＭＧ）、病理上的改变有相似之处。结论 提示其可作为研究人类ＰＭ的一个重要手段,为人类肌炎的发病机理及治疗提供理论依据。     

雷公藤多甙对实验性自身免疫性神经炎免疫状态的影响

目的 探讨雷公藤多甙(tripterygium polyglucoside,TPG)对实验性自身免疫性神经炎(experimental allergic neuritis,EAN)免疫状态的影响.方法 建立EAN大鼠模型,在其出现临床症状后连续给予TPG灌胃14 d,观察大鼠淋巴细胞增殖水平以及淋巴细胞钾通道mRNA和血清抗体表达水平的变化并分析其与临床症状的关联.结果 免疫后第23天,与对照组比较,EAN模型组的基础淋巴细胞增殖水平以及脂多糖和牛周围神经髓鞘(bovine peripheral myelin,BPM)诱导的细胞增殖水平显著增高[分别为(8.77±0.56)%比(4.67±0.39)%,(8.07±0.74)%比(7.24±0.30)%,(9.24±0.72)%比(7.22±0.67)%],淋巴细胞n型电压门控钾通道(voltage-gated K+ channel,Kv1.3)和中间电导钙激活钾通道(intermediate-conductance calcium-activated K+ channel,IKCa1)mRNA表达明显增高(分别为0.56±0.03比0.35±0.02,0.71±0.05比0.44±0.04),血清抗-BPM抗体水平亦显著升高(1 489.67±153.08比15.00±2.85);与EAN模型组比较,TPG治疗组的基础淋巴细胞增殖和BPM诱导的细胞增殖水平均明显降低[(7.96±0.45)%比(8.77±0.56)%,(8.09±0.52)%比(9.24±0.72)%],Kv1.3和IKCa1 mRNA表达降低(0.51±0.04 比0.56±0.03,0.64±0.04比0.71±0.05),抗-BPM抗体水平则无显著变化(1 341.08±346.42比1 489.67±153.08).结论 TPG通过抑制抗原特异性淋巴细胞增殖干预EAN的细胞免疫,该过程涉及淋巴细胞钾通道表达减少.TPG有可能成为吉兰-巴雷综合征的潜在治疗药物.     

豚鼠多发性肌炎动物模型肌酶谱的初步研究

检测了50只豚鼠实验性自身变态反应性肌炎(EAM)动物模型的磷酸肌酸激酶(CK)、乳酸脱氢酶(LDH)和谷一草转氨酶(AST)。发现35只CK升高,30只LDH升高,23只AST升高,其中以CK升高的例数最多,幅度最高。结合临床讨论了肌酶谱检测对多发性肌炎诊断的意义,提出肌酶谱升高亦是EAM模型建立的一个标准。     

多发性肌炎与皮肌炎

本病是较多见的肌肉疾病,属自体免疫性疾患。临床特点是肢体近端肌无力及萎缩。病理特点是肌肉有炎症浸润和肌纤维坏死。激素或免疫抑制剂治疗部分病例有效。所谓肌炎,以往既指原因已明的(如感染),也指原因不明的肌炎,现今则指病因不明或与免疫有关的肌炎。     

多发性硬化合并多发性肌炎一例

1 临床资料 患者女，44岁，因劳累后出现全身肌肉疼痛、乏力1个月，加重伴四肢浮肿2周，于2006-02-22入院。2000年曾因肢体麻木在作者医院诊断为“急性脊髓炎（C2-3）”，经治疗后好转；2003年出现双下肢乏力、麻木伴右侧胸背部痛诊断为“多发性硬化”（MS）。入院查体：四肢凹陷性浮肿，全身肌肉压痛，双上肢肌力Ⅴ级，双下肢肌力Ⅳ^＋级，双下肢腱反射未引出。     

神经肌炎与多发性肌炎的对比分析

目的 :为了认识神经肌炎的临床、神经电生理等方面特点 ,探讨其与多发性肌炎的关系。方法 :选取我院近 10年间收治的较典型的 11例神经肌炎病人 ,随机选取同期收治的多发性肌炎病人 2 9例 ,对此两组病人的临床表现、心脏并发症、对激素治疗的疗效、肌电图以及肌肉活检的结果给予对比研究。结果 :在神经肌炎组中 ,有 8例感觉障碍 (6例呈末梢型感觉障碍分布 ;2例呈多发性神经根神经炎表现 ) ;神经传导速度检查中 ,10例有运动传导速度明显减慢或引不出 ,1例电位波幅明显降低 ,呈轴索样损害的表现 ;多发性肌炎组病人均无感觉障碍 ,神经传导速度检查均正常。两组在其他临床表现及激素治疗效果上 ,血清CK增高 ,肌活检、肌电图方面无明显差异(P >0 0 5 )。结论 :神经肌炎是多发性肌炎中一种少见的特殊类型 ,除具有多发性肌炎的表现之外 ,同时还具有周围神经病的表现 ,两者间是很难区分的     

实验性肌炎动物模型的肌电图分析

目的 研究实验性肌炎动物模型的肌电图改变。方法 本文参照Dawkin方法用家兔骨骼肌匀浆多次免疫豚鼠制 作成实验性肌炎模型,动态观察其肌电图变化。结果 其肌电图改变表现为肌原性损害征象,与人类多发性肌炎(PM)相类似。 结论 模型建立是成功的,为人类PM的研究提供了依据。     

豚鼠实验变应性肌炎的药物干预治疗及肌肉病理研究

目的制作豚鼠多发性肌炎模型并探索其可能发病机制及相对安全可靠的治疗新方法。方法用免疫注射的方法制作动物模型并用强的松和动物类中药天龙(Gecko)进行分组干预对比治疗研究,以观察其症状、肌肉病理及肌酶谱变化的区别。结果免疫注射后所有豚鼠均出现不同程度的肌无力、体重减轻、肌酶增高等变化;肌肉病理表现为横纹结构消失、炎细胞浸润和肌细胞的变性、坏死;免疫组化染色见IgG沉积。结论(1)利用免疫注射的方法成功制作了豚鼠实验变应性肌炎动物模型;(2)豚鼠实验变应性肌炎肌肉病理改变主要为横纹肌呈散在分布或灶性分布的各种程度的肌细胞变性、坏死、再生和炎细胞浸润;间质小血管壁增厚,管腔狭窄甚至闭塞;肌膜、肌内膜和肌束膜中有IgG沉积;(3)动物类中药天龙对实验变应性肌炎具有与强的松相似的、比较明显的治疗修复和营养保护作用。     

Polymyositis presenting with cardiac manifestations: Report of two cases and review of the literature

We report two patients with severe cardiac manifestations at the time of the initial presentation of polymyositis. Both cases are unusual in that they presented with predominant cardiac disturbances, associated with muscle weakness. One patient had a typical clinical syndrome of congestive heart failure, and the second mimicked an acute myocardial infarction in which coronary angiography was normal. From our cases, we can emphasize that aside from characteristic symmetrical proximal muscle weakness, the clinical features of polymyositis may also include cardiac complications.     

炎症性肌病247例临床与病理研究

目的探讨多发性肌炎（PM）、间质性肌炎（IM）与神经肌炎（NM）的临床特点及神经肌肉活检的诊断价值。方法回顾分析247例炎症性肌病的临床表现及神经肌肉活检结果。结果3组临床表现相似,为近端肌无力、肌痛等;均有不同程度的肌酶增高,但PM组增高明显;IM和NM具有PM的病理改变,但炎性程度不及PM,又各有其特异性,IM组为炎性细胞浸润间质,NM组神经活检多有髓鞘脱失、炎性细胞浸润。结论PM、IM、NM炎性肌病的临床表现相似,诊断困难,需结合神经肌肉活检等辅助检查才能作出正确的诊断。     

蠕虫对多发性硬化动物模型的保护作用

一、多发性硬化(MS)和实验性自身免疫性脑脊髓炎多发性硬化是中枢神经系统(CNS)白质炎症脱髓鞘性自身免疫性疾病,临床主要表现为缓解复发和阶梯进展的视力、运动和平衡障碍。MS按疾病的病程分为以下几种类型:缓解复发型、原发进展和继发进展型。MS病情的进展是髓鞘抗原特异性T细胞,以髓鞘为靶,导致CNS的炎症浸润,最后导     

The role of interleukin-17 in immune-mediated inflammatory myopathies and possible therapeutic implications

The idiopathic inflammatory myopathies are a heterogeneous group of autoimmune muscle disorders with distinct clinical and pathological features and underlying immunopathogenic mechanisms. Traditionally, CD4⁺ Th1 cells or CD8⁺ cytotoxic effector T cells and type I/II interferons have been primarily implicated in the pathogenesis of the inflammatory myopathies. The presence of IL-17A producing cells in the inflamed muscle tissue of myositis patients and the results of in vitro studies suggest that IL-17A and the Th17 pathway may also have a key role in these diseases. The contribution of IL-17A to other chronic inflammatory and autoimmune diseases has been well established and clinical trials of IL-17A inhibitors are now at an advanced stage. However the precise role of IL-17A in the various forms of myositis and the potential for therapeutic targeting is currently unknown and warrants further investigation.     

实验性肌炎的治疗

为探索治疗多发性肌炎的有效方法，我们制作了豚鼠实验性自身免疫性肌炎（ＥＡＭ）模型，用强的松、雷公藤多甙、消炎痛和黄芪分组对照治疗，通过对动物的症状观察、肌电图、肌酶谱、肌肉病理检查结果分析，认为雷公藤多甙与强的松对ＥＡＭ有相近的良好疗效，黄芪次之，消炎痛无效。     

Current status and perspective of gene therapy on dystrophic animal model]

Duchenne muscular dystrophy (DMD) is an X-linked, lethal muscle disorder caused by mutations in the dystrophin gene. An adeno-associated virus (AAV) vector-mediated gene transfer is one of attractive approaches to the treatment of DMD, though it has a limitation in insertion size up to 4.9 kb. Therefore, a full-length dystrophin cDNA (14 kb) cannot be incorporated into an AAV vector. We previously generated micro-dystrophin transgenic dystrophin-deficient mdx mice. Micro-dystrophin CS1 transgenic mdx mice showed almost complete amelioration of dystrophic phenotypes. We, therefore, constructed an AAV vector expressing micro-dystrophin deltaCS1, a modified version of CS1, driven by skeletal muscle-specific MCK promoter, since the MCK promoter in AAV vector drives longer expression of the LacZ gene than the CMV promoter in skeletal muscle. We injected the AAV-MCK deltaCS1 into anterior tibial (TA) muscles of 5-week-old or 10-day-old mdx mice. Dystrophic phenotypes were largely improved in both injections. Especially in the latter occasion, less than 20% of muscle fibers were microdystrophin positive at 24 weeks after the injection, but specific tetanic force of the injected muscle was not statistically different from that of control normal muscle. In conclusion, deltaCS1 micro-dystrophin introduced by an AAV vector could be a powerful tool for the gene therapy of DMD. A bigger animal model, canine X-linked muscular dystrophy will contribute to pre-clinical study of gene therapy.     

Novel oral drug administration in an animal model of neuroleptic therapy

A novel method of oral drug administration was used in a neuroleptic animal study. Seventy male Sprague-Dawley rats were randomly subdivided into four groups, which were treated with clozapine, haloperidol, diazepam or a vehicle solution (5% sucrose solution). Oral drug treatment was achieved by training the rats to drink the drug of choice mixed with five percent sucrose or vehicle solution from a syringe. Within 3-4 weeks the haloperidol group developed vacuous chewing movement, which did not disappear with discontinuation of the drug. Significant weight gain was observed for all drug groups in relation to the control group, whereas only the diazepam group showed a significant increase in response latency on the disengage test of sensorimotor function, which disappeared with drug withdrawal. A novel means of testing the motivational status showed that all drug-treated groups engaged in eating chocolate before grooming (t=11.69, p<0.001), whereas the control group showed no specific tendency towards either task. Furthermore, there was a significant delay in grooming for the haloperidol group compared to the other drug groups and controls. In conclusion, a novel method of oral drug administration with minimum stress was introduced that was sufficient to cause the described changes in behavioural parameters. Additionally, the combination of tests used provided an efficient discrimination between the behavioural effects of clozapine, haloperidol and diazepam in rodents.     

Effect of combined therapy with thrombolysis and citicoline in a rat model of embolic stroke

An approach combining reperfusion mediated by thrombolytics with pharmacological neuroprotection aimed at inhibiting the physiopathological disorders responsible for ischemia-reperfusion damage, could provide an optimal treatment of ischemic stroke. We investigate, in a rat embolic stroke model, the combination of rtPA with citicoline as compared to either alone as monotherapy, and whether the neuroprotector should be provided before or after thrombolysis to achieve a greater reduction of ischemic brain damage. One hundred and nine rats have been studied: four were sham-operated and the rest embolized in the right internal carotid artery with an autologous clot and divided among 5 groups: 1) control; 2) iv rtPA 5 mg/kg 30 min post-embolization 3) citicoline 250 mg/kg ip x3 doses, 10 min, 24 h and 48 h post-embolization; 4) citicoline combined with rtPA following the same pattern; 5) rtPA combined with citicoline, with a first dose 10 min after thrombolysis. Mortality, neurological score, volume of ischemic lesion and neuronal death (TUNEL) after 72 h and plasma levels of IL-6 and TNF-alpha, were considered to assess ischemic brain damage. Compared with controls, the use of citicoline after thrombolysis produced the greatest reduction of mortality caused by the ischemic lesion (p<0.01), infarct volume (p=0.027), number of TUNEL positive cells in striatum (p=0.014) and plasma levels of TNF-alpha at 3 h (p=0.027) and 72 h (p=0.011). rtPA induced reperfusion provided a slight non-significant reduction of infarct volume and neuronal death, but it reduced mortality due to brain damage (p<0.01) although an increase in the risk of fatal bleeding was noted. CiT as monotherapy only produced a significant reduction of neuronal death in striatum (p=0.014). The combination of CiT before rtPA did not add any benefit to rtPA alone. The superiority of the combined treatment with rtPA followed by citicoline suggests that early reperfusion should be followed by effective neuroprotection to inhibit ischemia-reperfusion injury and better protect the tissue at risk.