miR-223 / mTOR / S6K通路与类风湿关节炎活动性和抗体水平的相关性

白文花; 李向培; 刘娟; 刘焱; 蒋真

doi:10.16766/j.cnki.issn.1674-4152.003868

miR-223 / mTOR / S6K通路与类风湿关节炎活动性和抗体水平的相关性

doi: 10.16766/j.cnki.issn.1674-4152.003868

白文花¹,
李向培²,
刘娟³,
刘焱³,
蒋真^{1, 3, ,}

1.
徐州医科大学淮安临床学院风湿免疫科, 江苏淮安 223300
2.
中国科学技术大学附属第一医院风湿免疫科, 安徽合肥 230001
3.
南京医科大学附属淮安市第一人民医院风湿免疫科, 江苏淮安 223300

基金项目:

江苏省第五期“333工程”科研资助项目 BRA2020226

详细信息

通讯作者:
蒋真，E-mail: docjiang@126.com

中图分类号: R593.22
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- 文章访问数: 7
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- 被引次数: 0
出版历程
- 收稿日期: 2024-05-12
- 网络出版日期: 2025-03-27

Correlations between miR-223/ mTOR/ S6K pathway and the activity of rheumatoid arthritis and antibody levels

BAI Wenhua¹,
LI Xiangpei²,
LIU Juan³,
LIU Yan³,
JIANG Zhen^{1, 3
, ,}

1.
Department of Rheumatology and Immunology, the Huaian Clinical College of Xuzhou Medical University, Huaian, Jiangsu 223300, China

摘要

摘要: 目的探讨类风湿关节炎(RA) 患者滑膜组织中miR-223表达与mTOR / S6K通路的相关性及miR-223 / mTOR / S6K通路与疾病活动性和抗体水平的相关性。方法选取2016年1月—2017年12月淮安市第一人民医院风湿免疫科住院的17例中重度RA住院患者和同期9例因膝骨关节炎(OA)手术住院的患者。超声引导下获取或由骨科医生术中获取膝关节滑膜组织。QRT-PCR检测滑膜组织中mTOR、S6K、RPS6 mRNA和miR-223表达水平。分析2组间miR-223水平以及mTOR、S6K、RPS6 mRNA水平的差异。RA组分析miR-223表达水平与mTOR、S6K、RPS6 mRNA水平的相关性, 并分析miR-223水平和mTOR、S6K、RPS6 mRNA水平与疾病活动性指标和抗环瓜氨酸肽抗体(抗CCP抗体)的相关性。结果 RA组miR-223水平较OA组显著升高(P < 0. 001), RA组S6K、RPS6 mRNA水平较OA组均显著降低(P < 0.05), RA组与OA组mTOR mRNA表达水平差异无统计学意义。RA组miR-223表达水平与S6K、RPS6 mRNA水平呈负相关关系(P < 0.05), miR-223表达水平与mTOR mRNA水平无相关性。RA组miR-223、mTOR mRNA水平与血清抗CCP抗体水平呈负相关关系(P < 0.05), RPS6 mRNA水平与血清抗CCP抗体水平呈正相关关系(P=0.009)。RA组miR-223表达水平与血清CRP水平呈正相关关系(P=0.043), RPS6、mTOR和S6K mRNA水平与血清CRP水平均无相关性。结论 RA患者膝关节滑膜组织中存在miR-223 / mTOR / S6K通路异常, 且与抗CCP抗体、CRP水平相关, 为RA发病机制的进一步研究指明了方向。
- 类风湿关节炎 /
- miR-223 /
- mTOR / S6K通路 /
- C-反应蛋白 /
- 抗CCP抗体
Abstract: Objective To investigate the expression levels of miR-223 and the mTOR / S6K pathway in synovial tissues of rheumatoid arthritis (RA) and their correlation with disease activity and antibody levels. Methods A total of 17 RA patients who were hospitalized in the Department of Rheumatology and Immunology of Huaian First People' s Hospital from January 2016 to December 2017 with moderate to severe disease RA were selected, along with 9 patients hospitalized for knee osteoarthritis (OA) surgery as controls. The synovial tissue from the knees of RA patients was obtained under the guidance of ultrasound, while tissue from OA patients were obtained by orthopedic surgeons. The expression levels of mTOR, S6K, RPS6 mRNAs, and miR-223 level in the synovial tissue were detected by qRT-PCR. Differences in miR-223 level and mRNA levels of mTOR, S6K, and RPS6 between the two groups were compared. The correlations between the level of miR-223 and the mRNA levels of mTOR, S6K, and RPS6, as well as anti-CCP antibody and disease activity indicators, were analyzed in the RA group. Results The miR-223 level in the RA group was significantly increased compared with the OA group (P < 0. 001), while the mRNA levels of S6K and RPS6 in the RA group were significantly decreased compared with the OA group (P < 0.05), There was no statistically significant difference in the expression level of mTOR mRNA between the RA group and the OA group. The miR-223 level in the RA group was negatively correlated with the mRNA levels of S6K and RPS6 (P < 0.05), but no significant correlation was found between miR-223 level and the level of mTOR mRNA. The levels of miR-223 and mTOR mRNA in the RA group were negatively correlated with the serum antiCCP antibody level (P < 0.05), while the level of RPS6 mRNA was positively correlated with the anti-CCP antibody level (P=0.009). The miR-223 level in the RA group was positively correlated with the serum CRP level (P=0.043), There was no correlation between the mRNA levels of RPS6, mTOR, and S6K and the CRP level. Conclusion An abnormal miR-223/ mTOR / S6K pathway exists in the synovial tissue of RA knee joints, correlating with the levels of anti-CCP antibody and CRP, indicating the potential pathways for further research into the pathogenesis of RA.
- Rheumatoid arthritis /
- miR-223 /
- mTOR / S6K pathway /
- C-reactive protein /
- Anti-CCP antibody

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表 1 RA组与OA组患者基本特征

Table 1. Basic characteristics of patients in RA group and OA group

组别	例数	年龄(x±s，岁)	性别(男性/ 女性，例)	病程[M(P₂₅, P₇₅)，月]	DAS28-ESR (x±s，分)	DAS28-CRP (x±s，分)	ESR[M(P₂₅, P₇₅)，mm/h]	CRP[M(P₂₅, P₇₅)，mg/L]	压痛关节数(x±s，个)	肿胀关节数(x±s，个)	抗CCP抗体[M(P₂₅, P₇₅)，RU/mL]	RF[M(P₂₅, P₇₅)，IU/mL]
RA组	17	55.3±9.6	4/13	120.0(30.0，240.0)	6.54±1.74	6.02±1.67	79.0(37.5，104.0)	49.3(31.2，124.5)	10.7±9.1	9.7±8.0	553.1(78.4，673.0)	495.2(25.1，344.5)
OA组	9	49.8±15.0	5/4	4.5(0.8，15.8)			10.0(8.0~14.0)	2.4(1.6，4.3)			21.9(19.1，23.7)	15.0(11.5，19.0)

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表 2 RA组与OA组膝关节滑膜组织中miR-223和mTOR、S6K、RPS6 mRNA水平比较[M(P₂₅, P₇₅)]

Table 2. Comparison of miR-223 and mTOR, S6K, and RPS6 mRNA levels in synovial tissues of knee joints between RA and OA groups[M(P₂₅, P₇₅)]

组别	例数	miR-223	S6K mRNA	RPS6 mRNA	mTOR mRNA
RA组	17	5.26(2.65，9.99)	0.54(0.28，0.76)	0.69(0.45，0.93)	1.31(0.92，2.74)
OA组	9	0.73(0.52，2.26)	0.95(0.73，1.48)	1.06(0.90，1.34)	1.02(0.88，1.83)
Z值		-3.598	-2.738	-2.919	-1.154
P值		< 0.001	0.007	0.004	0.258

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