肌肉活检中ER诱导自噬标志物的表达水平与特发性炎症性肌病病情的相关性

Correlation between the expression of ER-induced autophagy markers in muscle biopsy and idiopathic inflammatory myopathy

目的探讨肌肉活检中ER诱导自噬标志物的表达水平与特发性炎症性肌病(Idiopathic inflammatory myopathy,IIM)病情的相关性。方法37例免疫介导坏死性肌病(Immune-mediated necrotizing myopathy,IMNM)患者、14例皮肌炎(Dermatomyositis,DM)患者、6例抗合成酶综合征(Antisynthase syndrome,ASS)患者和10例对照者纳入研究;采用组织学切片、Western blot和实时定量聚合酶链式反应(Polymerase chain reaction,PCR)检测内质网应激诱导自噬通路的表达水平。结果内质网应激诱导的自噬途径在IMNM,DM和ASS患者的活检肌肉中被激活,骨骼肌中内质网伴侣蛋白、葡萄糖调节蛋白78(Glucose-regulating protein 78,GRP78)/免疫球蛋白结合蛋白(Immunoglobulin binding protein,BiP)表达水平与IMNM的自噬、肌纤维萎缩、肌坏死、肌再生和疾病活动性相关。结论内质网应激自噬与特发性炎症性肌病患者有关,并与IMNM的疾病活动性相关,内质网应激反应可能是IIM患者骨骼肌损伤和修复的原因。

Objective To investigate the correlation between the expression of ER-induced autophagy markers in muscle biopsy and idiopathic inflammatory myopathy(IIM).Methods Thirty-seven patients with immune-mediated necrotizing myopathy(IMNM),14 patients with dermatomyositis(DM),6 patients with anti-synthase syndrome(ASS),and 10 controls were included in the study.Histological sections,Western blot and real-time quantitative PCR were used to detect the expression of endoplasmic reticulum stress-induced autophagy pathway.Results Endoplasmic reticulum stress-induced autophagy pathway is activated in biopsied muscles of patients with IMNM,DM,and ASS,and the expression of endoplasmic reticulin,glucose-regulatory protein 78(GRP78)/BiP in skeletal muscle is associated with IMNM autophagy,muscle fiber atrophy,muscle necrosis,muscle regeneration,and disease activity.Conclusion Endoplasmic reticulum stress autophagy is associated with IIM patients and disease activity of IMNM,and the endoplasmic reticulum stress response may be the cause of skeletal muscle injury and repair in IIM.