磷脂酰肌醇3一激酶在ALS萎缩肌纤维中表达的意义

Significance of phosphatidyl inositol 3-kinase expression in amyotrophic lateral sclerosis atrophy muscle fibers

目的研究磷脂酰肌醇3．激酶（P13K）在肌萎缩侧索硬化（ALS）患者骨骼肌细胞中的表达及意义。探讨ALS肌纤维萎缩的发病机制。方法选取河北医科大学第三医院神经肌肉病科住院部自2005年6月至2013年1月收治的90例ALS患者临床资料．分析临床、血肌酸激酶及电生理特点。全部患者行开放式骨骼肌活检，冰冻连续切片，组织化学、酶学染色及P13K、神经细胞黏附分子（NCAM）免疫组织化学染色病理分析，电镜观察其超微结构。结果（1）ALS患者骨骼肌病理可见大量小角化肌纤维、萎缩肌纤维和核聚集现象。（2）PISK在萎缩肌纤维膜上呈阳性表达，NCAM在萎缩肌纤维中阴性表达。（3）电镜下萎缩肌纤维中存在典型的线粒体形态异常。结论（1）ALS骨骼肌细胞存在线粒体结构和功能异常。（2）ALS的肌纤维萎缩与肌细胞凋亡机制有关。（3）P13K的异常表达对ALS的诊断或有意义。

Objective To study the significance of phosphatidyl inositol 3-kinase （PI3K） expression in amyotrophic lateral sclerosis （ALS） atrophy muscle fibers and investigate the pathogenesis of muscle fiber atrophy. Methods The clinical data of 90 ALS inpatients, admitted to our hospital from June 2005 to January 2013, were collected; and the features of clinical manifestations, creatine kinase level and electrophysiology were investigated. All patients accepted open muscle biopsy; the frozen tissues were performed histochemical, ertzymology, anti-PI3K and nerve cell adhesion molecules （NCAM） monoclonal antibody immunohistochemistry staining; the pathological and ultrastructure characteristics were observed. Results A lot of small angular fibers, atrophy fibers and nuclear clump grouping were observed in skeletal muscle samples of ALS. PI3K positively expressed in sarcolemma of atrophy fibers, while NCAM negatively expressed. The pathologic changes of ultrastructure in transmission electromicroscope illustrated ALS atrophy fibers, having typical mitochondria paramorphia changes. Conclusion Mitochondria paramorphia changes and dysfunction are observed in ALS muscle fibers; atrophy fibers of ALS are related to muscle fiber apoptosis.