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急性痛风性关节炎患者血浆中微小RNA的表达以及秋水仙碱和依托考昔对微小RNA差异表达的影响

Expression of microRNAs in the plasma of patients with acute gouty arthritis and the effects of colchicine and etoricoxib on the differential expression of microRNAs.

作者信息

Liu Peng, Chen Ying, Wang Bin, Wang Zhongchao, Li Changgui, Wang Yangang

机构信息

Department of Endocrinology, the Affiliated Hospital of Qingdao University, Qingdao, China.

Department of Endocrinology, Laiwu Hospital Affiliated to Taishan Medical College, Laiwu, China.

出版信息

Arch Med Sci. 2019 Jul;15(4):1047-1055. doi: 10.5114/aoms.2018.75502. Epub 2018 Apr 26.

Abstract

INTRODUCTION

To determine the microRNA (miRNA) expression profiles in the plasma of acute gouty arthritis (AGA) patients and investigate the effects of colchicine and etoricoxib treatment on the differential expression of miRNAs.

MATERIAL AND METHODS

Exiqon miRCURYLNA microRNA Array was used for miRNA expression profiling in AGA. Two of the 21 differentially expressed miRNAs were confirmed using quantitative real-time polymerase chain reaction (qRT-PCR). A randomized, double-blind, parallel-controlled design was used to divide 160 AGA patients into colchicine and etoricoxib groups. Changes in 2 differentially expressed miRNAs, interleukin-1 (IL-1) β, cyclooxygenase-2 (COX-2) and joint pain scores were detected.

RESULTS

Compared with normal subjects and asymptomatic hyperuricemia (HUA) patients, plasma of AGA contained 21 differentially expressed miRNAs. qRT-PCR indicated specific downregulation of miR-223-3p and miR-451a in AGA. There were no statistically significant differences in the baseline characteristics between colchicine and etoricoxib groups. Furthermore, no significant difference in joint pain scores after 5- and 10-day treatment were found between groups ( > 0.05). Comparison of differences between pre- and 5-day post-treatment values confirmed that the upregulation of miR-223-3p and downregulation of IL-1β induced by colchicine were more significant than etoricoxib ( < 0.05). However, the latter outperformed the former in the upregulation of miR-451a and downregulation of COX-2 ( < 0.05). After 10-day treatment, the magnitude of miR-223-3p upregulation and IL-1β downregulation in the colchicine group was significantly higher than in the etoricoxib group, while the etoricoxib group had higher expression of miR-451a and lower expression of COX-2 than the colchicine group ( < 0.05).

CONCLUSIONS

In AGA patients, 21 differentially expressed miRNAs were detected in the plasma. Colchicine could upregulate miR-223-3p and downregulate IL-1β in the plasma, while etoricoxib may treat AGA by upregulating miR-451a and downregulating COX-2.

摘要

引言

确定急性痛风性关节炎(AGA)患者血浆中的微小RNA(miRNA)表达谱,并研究秋水仙碱和依托考昔治疗对miRNA差异表达的影响。

材料与方法

使用Exiqon miRCURYLNA微小RNA芯片对AGA患者进行miRNA表达谱分析。使用定量实时聚合酶链反应(qRT-PCR)对21种差异表达的miRNA中的两种进行了验证。采用随机、双盲、平行对照设计,将160例AGA患者分为秋水仙碱组和依托考昔组。检测2种差异表达的miRNA、白细胞介素-1(IL-1)β、环氧化酶-2(COX-2)的变化及关节疼痛评分。

结果

与正常受试者和无症状高尿酸血症(HUA)患者相比,AGA患者血浆中有21种差异表达的miRNA。qRT-PCR表明AGA患者中miR-223-3p和miR-451a特异性下调。秋水仙碱组和依托考昔组的基线特征无统计学显著差异。此外,两组在治疗5天和10天后的关节疼痛评分无显著差异(P>0.05)。治疗前与治疗后5天数值差异的比较证实,秋水仙碱诱导的miR-223-3p上调和IL-1β下调比依托考昔更显著(P<0.05)。然而,依托考昔在miR-451a上调和COX-2下调方面优于秋水仙碱(P<0.05)。治疗10天后,秋水仙碱组miR-223-3p上调幅度和IL-1β下调幅度显著高于依托考昔组,而依托考昔组miR-451a表达高于秋水仙碱组,COX-2表达低于秋水仙碱组(P<0.05)。

结论

在AGA患者血浆中检测到21种差异表达的miRNA。秋水仙碱可上调血浆中miR-223-3p并下调IL-1β,而依托考昔可能通过上调miR-451a和下调COX-2治疗AGA。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/658e/6657241/f4389571fb3f/AMS-15-32699-g001.jpg

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