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黑色素瘤缺失因子炎性小体通路相关蛋白在类风湿关节炎与骨关节炎滑膜差异表达分析

Differential expression analysis of absent in melanoma 2-inflammasome pathway associated protein in rheumatoid arthritis and osteoarthritis synovium
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摘要 目的比较RA与OA滑膜标本黑色素瘤缺失因子(AIM2)炎性小体通路的表达水平差异。方法收集膝关节炎滑膜组织标本,RA 41例与OA 26例,采用辣根过氧酶免疫组织化学染色法,检测AIM2炎性小体通路相关蛋白,包括:AIM2、凋亡相关斑点样蛋白(ASC)、胱天蛋白酶-1(caspase-1)、IL-1β的表达水平差异。并根据阳性程度进行半定量评分(H评分)。H评分结果与临床指标ESR、CRP进行相关性分析。采用t检验分析RA与OA滑膜染色H评分,H评分与ESR、CRP的相关性分析采用Spearman相关性分析。结果RA滑膜组织中AIM2的H评分为(132±7),高于OA滑膜组织中AIM2的H评分(54±8),2组间比较差异有统计学意义(t=7.42,P<0.01);RA滑膜组织中ASC的H评分为(107±9)分,高于OA滑膜组织中ASC的H评分(74±6),2组间比较差异有统计学意义(t=2.36,P<0.05);RA滑膜组织中caspase-1的H评分为(99±5),高于OA滑膜组织中caspase-1的H评分(74±10),2组间比较差异有统计学意义(t=2.15,P<0.05);RA滑膜组织中IL-1β的H评分为(118±11),高于OA滑膜组织中IL-1β的H评分(76±7),2组间比较差异有统计学意义(t=3.30,P<0.05)。AIM2与ESR呈中等强度相关性[r=0.74,P<0.01,95%置信区间(95%CI)(0.38,0.9)]、CRP呈中等强度相关性[r=0.65,P<0.05,95%CI(0.25,0.86)]。ASC与ESR[r=0.5,P<0.05,95%CI(0.16,0.74)],CRP[r=0.42,P<0.05,95%CI(0.05,0.69)]呈中等强度相关性。IL-1β与ESR[r=0.62,P<0.01,95%CI(0.31,0.81)],CRP[r=0.41,P<0.05,95%CI(0.05,0.67)]呈中等强度相关性。caspase-1与ESR、CRP未见明显相关性(P>0.05)。结论RA滑膜中AIM2炎性小体通路相关蛋白包括AIM2、ASC、caspase-1和IL-1β表达高于OA,并且与活动度呈正相关;AIM2炎性小体通路的激活可能是RA活动的机制。 Objective To compare the expression levels of absent in melanoma 2(AIM2)inflammasome pathways in rheumatoid arthritis(RA)and osteoarthritis(OA)synovial specimens.Methods Synovial tissue samples were collected from 41 RA and 26 OA patients,respectively.Horseradish peroxidase immunohi stochemical staining was used to detect AIM2 inflammasome pathway-related proteins,including AIM2,apoptosis-associated speck-like protein containing a CARD(ASC),caspase-1,and interleukin-1(IL-1β).A semi-quantitative score(H-score)was performed according to the degree of positiveness.Correlation analysis between H-score results and clinical indicators of erythrocyte sedimentation tate(ESR)and C-reactive protein(CRP)were performed.The H score between RA and OA was analyzed by t test and Spearman correlation analysis were utilized for correlation analysis between H score and ESR and CRP.Results The H scores of AIM2 protein in RA synovial tissues was(132±7)and(54±8)in OA synovial tissues(t=7.42,P<0.01).The H scores of ASC protein in RA synovial tissues was(107±9)and(74±6)in OA synovial tissues(t=2.36,P<0.05).The H scores of caspase-1 protein in RA synovial tissues was(99±5)and(74±10)in OA synovial tissues(t=2.15,P<0.05).The H scores of IL-1βprotein in RA synovial tissues was(118±11)and(76±7)in OA synovial tissues(t=3.30,P<0.05).In the correlation analysis,AIM2 was positively correlated with ESR[r=0.74,P<0.01,95%CI(0.38,0.9)],and ASC was positively correlated with ESR[r=0.5,P<0.05,95%CI(0.16,0.74)],IL-1βwas positively correlated with ESR[r=0.62,P<0.05,95%CI(0.31,0.81)],and the difference was statistically significant(P<0.05).At the same time,AIM2 was positively correlated with CRP[r=0.65,P<0.05,95%CI(0.25,0.86)];ACS was positively correlated with CRP[r=0.42,P<0.05,95%CI(0.05,0.69)].IL-1βwas positively correlated with C-reactive Protein[r=0.41,P<0.05,95%CI(0.05,0.67)]and positively correlated with C-reactive protein,and the difference was statistically significant(P<0.05).Conclusion:The expression of AIM2 inflammasome pathway-related proteins in RA synovium,including AIM2,ASC,caspase-1,and IL-1β,is higher than that of OA and are positively correlated with disease activity.Activation of AIM2 inflammasome pathway may be associated with the pathogenesis of RA disease activity.
作者 邱富娟 陈永 赵晓峰 陈恩生 左芳芳 袁毅 吴自勋 苏琴 肖长虹 Qiu Fujuan;Chen Yong;Zhao Xiaofeng;Chen Ensheng;Zuo Fangfang;Yuan Yi;Wu Zixun;Su Qin;Xiao Changhong(Department of Rheumatology and Immunology,Integrated Traditional Chinese and Western Medicine Hospital,Southern Medical University,Guangzhou 510315,China;Department of Pathology,Integrated Traditional Chinese and Western Medicine Hospital,Southern Medical University,Guangzhou 510315,China)
出处 《中华风湿病学杂志》 CAS CSCD 北大核心 2020年第6期383-387,I0002,共6页 Chinese Journal of Rheumatology
基金 国家自然科学基金(81673723)。
关键词 关节炎 类风湿 黑色素瘤缺失因子炎性小体 红细胞沉降率 C反应蛋白质 Arthritis rheumatoid Absent in melanoma 2-inflammasome Erythrocyte sedimentation tate C-reactive protein
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