细胞焦亡非经典途径蛋白质在皮肌炎/多发性肌炎患者肌肉组织中的表达及意义  

Expression and significance of non-canonical pyroptosis pathway-related proteins in muscle tissues of patients with dermatomyositis/polymyositis

作　　者：邓蕊 柴克霞[1] Deng Rui;Chai Kexia(Department of Rheumatology and Immunology,Qinghai University Affiliated Hospital,Xining 810001,China)

机构地区：[1]青海大学附属医院风湿免疫科,西宁810001

出　　处：《中华微生物学和免疫学杂志》2021年第10期771-777,共7页Chinese Journal of Microbiology and Immunology

基　　金：青海省科技厅应用基础研究科技计划项目(2019-ZJ-7094)。

摘　　要：目的检测caspase-4、caspase-5、gasdermin D(GSDMD)、核苷酸结合寡聚化结构域NOD样受体蛋白质3(nucleotide-binding oligomerization domain-like receptor protein 3,NLRP3)、泛连接蛋白质1(Pannexin-1)及P2X7在皮肌炎(dermatomyositis,DM)和多发性肌炎(polymyositis,PM)患者肌肉组织中的表达水平,研究探讨细胞焦亡非经典途径蛋白质在DM和PM发病机制中的作用及意义。方法选取2019年1月—2020年9月在我院就诊的DM患者13例,PM患者9例及因单纯骨科创伤行清创术的无其他伴随疾病的志愿者20例。采用HE染色检测各组肌肉组织的病理改变,并采用免疫组织化学法检测各组肌肉组织中caspase-4、caspase-5、GSDMD、NLRP3、Pannexin-1和P2X7的表达水平。结果(1)HE染色显示对照组肌肉组织肌纤维形态结构基本正常,未见明显炎性细胞浸润及萎缩、变性、坏死;DM组和PM组肌纤维大小不一、粗细不等,有大量炎性细胞浸润,可见不同程度的萎缩、变性、坏死;DM组和PM组患者肌肉组织HE染色病理学评分显著高于对照组,差异有统计学意义(P<0.05);(2)免疫组织化学染色显示caspase-4、caspase-5、GSDMD、NLRP3、Pannexin-1及P2X7在DM组和PM组肌肉组织中的表达均高于对照组(P<0.05);(3)Pearson相关分析提示DM组和PM组肌肉组织HE染色病理学评分和caspase-4、caspase-5、GSDMD、NLRP3、Pannexin-1以及P2X7的免疫组化评分均呈正相关(P<0.05);caspase-4、caspase-5的免疫组化评分与GSDMD和Pannexin-1的免疫组化评分均成正相关(P<0.05);GSDMD与NLRP3的免疫组化评分均成正相关(P<0.05);Pannexin-1与P2X7的免疫组化评分均成正相关(P<0.05)。结论细胞焦亡非经典途径蛋白质可能参与了DM和PM的发病过程,并且可能是通过促进炎症反应来参与其发病,提示在DM和PM的免疫发病机制中非经典途径的细胞焦亡起着至关重要作用。Objective To detect the expression of cysteinyl aspartate specific proteinase 4(caspase-4),caspase-5,gasdermin D(GSDMD),nucleotide-binding oligomerization domain-like receptor protein-3(NLRP3),Pannexin-1 and P2X7 involved in non-canonical pyroptosis pathway in muscle tissues of patients with dermatomyositis(DM)/polymyositis(PM)and to investigate the roles and significance of them in the pathogenesis of DM and PM.Methods Altogether 13 DM patients,nine PM patients and 20 volunteers(control group)treated in the Affiliated Hospital of Qinghai University from January 2019 to September 2020 were enrolled in the present study.The 20 volunteers with no additional concomitant diseases underwent debridement due to simple orthopedic trauma.Pathological changes in muscle tissues were detected by hematoxylin&eosin(HE)staining.Expression of caspase-4,caspase-5,GSDMD,NLRP3,Pannexin-1 and P2X7 in muscle tissues was measured using immunohistochemistry(IHC).Results(1)HE staining results showed that the muscle fibers in the control group had basically normal morphology and structure with no obvious inflammatory cell infiltration,atrophy,degeneration or necrosis.However,the size and thickness of muscle fibers in DM and PM groups were different with excessive inflammatory cell infiltration,atrophy,degeneration and necrosis to varying degrees.Moreover,the pathological scores of HE staining in muscle tissues of DM and PM groups were significantly higher than that of the control group and the differences were of statistical significance(P<0.05).(2)IHC staining results suggested that the expression of caspase-4,caspase-5,GSDMD,NLRP3,Pannexin-1 and P2X7 in muscle tissues was higher in DM and PM groups than in the control group(P<0.05).(3)As indicated by Pearson correlation analysis,the pathological scores of HE staining in muscle tissues of DM and PM groups were positively correlated with the IHC scores of caspase-4,caspase-5,GSDMD,NLRP3,PAnnexin-1 and P2X7(P<0.05).Furthermore,the IHC scores of caspase-4 and caspase-5 were positively corr

关 键 词：皮肌炎 多发性肌炎 细胞焦亡 Caspase-4 Caspase-5 GSDMD NLRP3 Pannexin-1 P2X7 

分 类 号：R593.26[医药卫生—内科学]