多发性肌炎大鼠模型制作的对比

目的 为兔骨骼肌匀浆多点皮下注射制备多发性肌炎大鼠模型的方法探索最佳的实验对象和实验条件.方法 SD大鼠、Westar大鼠和Lewis大鼠根据品种、性别、免疫物剂量等因素分组建模,取股四头肌进行组织病理学检查,比较各组之间成模比例、死亡比例、肌肉病理评分等观察指标的差异.结果 ①三个大鼠品种中,Lewis大鼠模型成功率最高,且实验耐受性最好,相同免疫剂量组的死亡比例最低.②相同免疫剂量下雌性组的成模比例均高于雄性组,而肌肉病理评分在不同性别组之间差异不明显.③雌性Lewis大鼠中,注射兔骨骼肌匀浆蛋白剂量从8 mg/kg增加至10mg/kg时,成模比例及模型病理评分明显升高;但从10mg/kg增加至12 mg/kg时,成模比例及模型病理评分无明显变化,而大鼠死亡比例升高.④雌性Lewis成模大鼠中,免疫2周时即可见到骨骼肌纤维大小不一、横纹消失及核内移,免疫4～5周时可见骨骼肌纤维坏死、非坏死肌纤维及间质血管周围炎细胞浸润等典型病变,继续免疫至7周时骨骼肌病变未继续加重.结论 采用兔骨骼肌匀浆多点皮下注射方法制备多发性肌炎大鼠模型时,选择雌性Lewis大鼠作为实验对象,给予兔骨骼肌匀浆10mg/kg连续免疫5周可出现与人类多发性肌炎非常相似的骨骼肌病变,且成模比例高、死亡比例低,造模效果理想.     

Corticosteroid-sparing effect of tacrolimus in the initial treatment of dermatomyositis and polymyositis

Objective. In the treatment of polymyositis (PM) and dermatomyositis (DM), muscle inflammation and underlying autoimmunity need to be suppressed promptly; however, catabolic effects of corticosteroids such as myopathy can be detrimental in PM/DM. In this study, we aimed to assess the corticosteroid-sparing effect of tacrolimus in the initial treatment of PM/DM.

Methods. We retrospectively identified 19 PM/DM patients who received initial treatment with prednisolone at an initial dose of 1 mg/kg/day (Conventional Monotherapy, our standard therapy before 2008) and 23 patients with tacrolimus plus prednisolone at an initial dose 0.8 mg/kg/day (Tacrolimus Combination, our standard therapy after 2008). Data until 36 months after commencing treatment were collected.

Results. There were no statistically significant differences in baseline characteristics between two groups. Median daily dose of prednisolone in the Tacrolimus Combination Group was significantly lower than that in the Conventional Monotherapy Group during the study period, whereas the proportion of patients who required additional immunosuppressive medications for remission induction was comparable. Remission was achieved in all patients, except one who died of refractory interstitial lung disease after receiving Conventional Monotherapy. The time required for creatine kinase normalization and relapse rate was comparable between two groups. The period of hospitalization for initial treatment was significantly shorter and survival without serious infection or relapse tended to be longer in the Tacrolimus Combination than the Conventional Monotherapy.

Conclusion. This study provides real-life data which demonstrate that tacrolimus has a corticosteroid-sparing effect and reduces the length of hospitalization period for the initial treatment of PM/DM.     

甲状腺功能减退性多发性肌炎样综合征57例回顾分析

目的了解甲状腺功能减退性多发性肌炎样综合征患者的临床特点。方法回顾分析1997--2007年国内文献报道的53例及我院收治的4例患者的临床资料。结果甲状腺功能减退性多发性肌炎样综合征表现为近端肌无力伴不同程度肌痛，不伴肌肥大或肌强直，肌酶显著升高，肌电图和肌活检多无特异性改变，甲状腺素替代治疗疗效好。结论临床上对有肌病表现、肌酶显著升高的患者须注意有无甲状腺功能减退症。病程较长、病情严重或伴黏液性水肿的甲状腺功能减退症患者出现特异性肌肉表现、肌酶显著升高时应考虑多发性肌炎样综合征。     

Effect of physical training on the proportion of slow‐twitch type I muscle fibers,a novel nonimmune‐mediated mechanism for muscle impairment in polymyositis or dermatomyositis

Objective

To compare muscle fiber type composition and muscle fiber area in patients with chronic polymyositis or dermatomyositis and healthy controls, and to determine whether physical training for 12 weeks could alter these muscle characteristics.

Methods

Muscle fiber type composition and muscle fiber area were investigated by biochemical and immunohistochemistry techniques in repeated muscle biopsy samples obtained from 9 patients with chronic myositis before and after a 12‐week exercise program and in healthy controls. Muscle performance was evaluated by the Functional Index (FI) in myositis and by the Short Form 36 (SF‐36) quality of life instrument.

Results

Before exercise, the proportion of type I fibers was lower (mean ± SD 32% ± 10%) and the proportion of type IIC fibers was higher (3% ± 3%) in patients compared with healthy controls. After exercise, percentage of type I fiber increased to 42% ± 13% (P < 0.05), and type IIC decreased to 1% ± 1%. An exercise‐induced 20% increase of the mean fiber area was also observed. The functional capacity measured by the FI in myositis and the physical functioning subscale of the SF‐36 increased significantly. Improved physical functioning was positively correlated with the proportion of type I fibers (r = 0.88, P < 0.01) and type II muscle fiber area (r = 0.70, P < 0.05).

Conclusion

Low muscle endurance in chronic polymyositis or dermatomyositis may be related to a low proportion of oxidative, slow‐twitch type I fibers. Change in fiber type composition and increased muscle fiber area may contribute to improved muscle endurance and decreased muscle fatigue after a moderate physical training program.     

Efficacy of combination treatment with cyclosporin A and corticosteroids for acute interstitial pneumonitis associated with dermatomyositis

Interstitial pneumonitis (IP) associated with polymyositis and dermatomyositis (PM/DM) is a serious complication that affects prognosis. We therefore undertook a retrospective multicenter study to examine the efficacy of a combination treatment with cyclosporin A (CsA) and corticosteroids. Fifty-three IP patients with PM/DM (9 PM, 44 DM) were analyzed. Thirty-two patients treated with CsA plus corticosteroids (9 PM, 23 DM) were included in the study. Four parameters, i.e., subjective symptoms, ausculatory sound, chest radiographs, and respiratory index, were serially evaluated. A general evaluation was performed 4 weeks after the start of the combination treatment. All patients with PM and chronic IP with DM, and 52% of those with acute IP with DM were graded as better than partially effective in the general evaluation. In contrast, all patients graded as progressive in the general evaluation had acute IP with DM. It is of note that in acute IP with DM, the survival rate of the group primarily treated with CsA and corticosteroids from the early stage of their disease was significantly higher than that of the group initially treated with corticosteroids alone (P = 0.049). In conclusion, a combination treatment of CsA and corticosteroids from the early stage of disease may be advantageous for patients with IP with PM/DM, especially acute IP with DM.     

特发性炎性肌病分型诊断标准的比较分析

目的 评价Bohan/Peter标准(B/P标准)与欧洲神经肌肉疾病中心(ENMC)标准对特发性炎性肌病分型诊断皮肌炎和多发性肌炎的准确性.方法 回顾性收集86例初诊为特发性炎性肌病患者的临床、实验室及骨骼肌病理资料,分别用B/P标准与ENMC标准进行分型诊断,比较两个标准诊断皮肌炎和多发性肌炎的异同性.数据分析采用SPSS 13.0软件系统进行非参数检验(Mann Whitney U检验)和一致性检验(Kappa分析)方法.结果 B/P标准诊断皮肌炎37例,多发性肌炎49例;ENMC标准诊断皮肌炎46例,多发性肌炎仅14例,其余为嗜酸细胞性肌炎1例、疑诊散发性包涵体肌炎9例,未能分型者5例,肢带型肌营养不良2B型11例.Kappa分析检验两个标准诊断皮肌炎一致性较好(κ=0.79),诊断多发性肌炎一致性差(κ=0.26).结论 B/P标准对多发性肌炎存在过度诊断、误诊风险.ENMC标准纳入免疫病理,增加了临床与病理诊断的排除标准,其分型诊断准确性优于B/P标准.     

Humoral aspects of polymyositis/dermatomyositis

Abstract

Evidence of the involvement of systemic autoimmunity has been observed in polymyositis/dermatomyositis (PM/DM). Autoantibodies directed against various cellular constituents have been detected in most patients with PM/DM, and about one-third of patients have autoantibodies (myositis-specific antibodies: MSAs) that are found specifically in myositis patients. These autoantibodies are closely associated with a characteristic clinical subgroup, and therefore help in establishing the correct diagnosis, classifying the myositis patients in a homogeneous subset, and facilitating the clinical and treatment follow-up. Autoantibodies to six of the aminoacyl tRNA synthetases are each associated with a similar syndrome marked by myositis, interstitial lung disease, arthritis, and other features constituting an "antisynthetase syndrome." Antibodies to other cytoplasmic antigens that are involved in protein synthesis or translation factors are seen in a small proportion of patients. Antisignal recognition particles are associated with severe, refractory myositis that differs significantly from antisynthetase syndrome. Antibodies to the nuclear antigen are specifically seen in patietnts with DM. Several autoantibodies, including anti-U1 RNP, anti-U2 RNP, anti-Ku, and anti-PM-Scl, have been associated with scleroderma–PM overlap. In recent years, these MSAs and their antigens have been characterized using molecular biology approaches. It is not known if the MSAs are involved in tissue injury or the pathogenesis of PM/DM. However, an understanding of the production mechanisms of these autoantibodies can provide insight into the etiology of this disorder.     

Severe subcutaneous generalized edema in a patient with dermatomyositis

Abstract

Subcutaneous generalized edema associated with dermatomyositis (DM)/polymyositis (PM) is extremely rare. Herein we report a case of severe subcutaneous generalized edema complicating DM. A 78-year-old woman was hospitalized in our department because of massive edema in the four limbs. Elevated muscle enzymes, heliotrope rash, results of electromyography, and muscle biopsy confirmed the diagnosis of DM. The absence of other diseases that could cause the symptoms indicated that massive edema was correlated with the pathophysiology of DM. Although myopathy and edema responded well to oral prednisolone, dysphagia persisted. We conclude that subcutaneous generalized edema can occur during the course of DM/PM, and subcutaneous vasculopathy may be involved in the pathogenesis of DM/PM.     

MiR-381通过靶向基质细胞衍生因子-1对多发性肌炎组织浸润的巨噬细胞的作用机制

目的 探讨miR-381通过靶向基质细胞衍生因子-1(SDF-1)对多发性肌炎(PM)组织浸润的巨噬细胞的作用机制.方法 通过兔肌球蛋白(1.5mg)、结核分枝杆菌(5mg)和百日咳毒素(500 ng)构建PM小鼠模型.将30只PM模型小鼠随机分为PM组和PM+miR-381组(每组15只),另取同期15只健康小鼠作为...