类风湿关节炎患者外周血miR-146a、miR-155与Ets-1、IRAK1的表达及临床意义
发布时间：2019-01-06 14:35
【摘要】：目的:研究类风湿关节炎(rheumatoid arthiritis,RA)患者外周血单个核细胞(peripheral blood mononuclear cells,PBMCs)中 miR-146a、miR-155 与 Ets-1、IRAK1和血浆中炎症因子的表达水平,同时结合临床指标分析以上因子及与RA病情的相关性,初步探讨上述几种因子在RA发病过程中的作用。方法:收集2015年9月至2016年5月在南方医院中医科住院RA患者44例,其中男性6例,女性38例。根据患者的病情活动度分为高活动组23例,其中男性4例,女性19例;低活动组21例,其中男性2例,女性19例。所有RA患者均符合2010年美国风湿学会(ACR)联合欧洲抗风湿联盟(EULAR)修订的RA分类标准。健康对照组为同期在南方医院体检科的体检者22例,其中男性6例,女性16例。两组在年龄及性别构成方面的差异无统计学意义。采用实时荧光定量聚合酶反应(RT-PCR)检测分离的PBMCs中的miR-146a、miR-155及Ets-1、IRAK1 mRNA的相对表达水平,同时ELISA检测血浆中Ets-1和IRAK1的蛋白水平,检测血浆中TNF-α、IL-1β、IL-2、IL-6、IL-17、IL-21 的水平,并与DAS28、CRP、ESR、RF、抗CCP、Hb、总补体等进行相关性分析。统计学处理采用t检验,非参数检验,单因素方差分析,Pearson、Spearman相关分析,以P0.05为差异有统计学意义。结果:miR-146a、miR-155在RA患者PBMCs中的相对表达水平显著高于健康对照组(P0.05),高活动组的表达水平明显高于低活动组(P0.05)、低活动组和健康对照组比较未发现统计学差异(P0.05);RA患者PBMCs的Ets-1 mRNA相对表达水平与健康对照组无统计学意义(P0.05),但高活动组中的相对表达水平显著低于低活动组和健康对照组(P0.05),低活动组与健康对照组无统计学差异(P0.05);RA患者中的IRAK1mRNA相对表达水平明显低于健康对照组(P0.05),高活动组显著低于健康对照组(P0.01)、低活动组显著低于健康对照组(P0.05),而高活动组与低活动组之间未发现有统计学差异(P0.05)。Ets-1、IRAKI在RA血浆中的蛋白表达水平与健康对照者无统计学差异(P0.05)。ELISA检测发现TNF-α、IL-1β、IL-6、IL-21的蛋白表达水平在RA患者血浆中表达增高的,而IL-2、IL-17在RA患者与健康对照者的血浆中无明显变化。相关性分析显示miR-155的表达水平与血沉正相关(r=0.319,P=0.042),与 Hb 成负相关(r=-0.386,PP=0.017);Ets-1 与 CRP负相关(r=-0.408,P,P=0.007);IRAK1 与 RF、DAS28、总补体负相关(r=-0.513,P=0.001;r=-0.332,P=0.029;r=-0.49,P=0.015)。结论:此次研究发现RA患者PBMCs的miR-146a、miR155相对表达水平增高,提示miR146a、miR155参与RA的发病,可能成为RA高活动的诊断标志物;Ets-1、IRAK1相对表达水平降低,可能参与RA的调控;RA患者血浆中TNF-α IL-1β、IL-6、IL-21炎症因子表达明显增高,可能在RA发病中扮演重要角色,TNF-α、IL-6与CRP、ESR、CRP呈正相关,对病情活动的判断有一定的参考意义。由于本研究样本量有限,miR-146a、miR1 55和Ets-1、IRAK1参与RA发病的关系及炎症因子的变化有待后续大样本研究证实,其相关调控机制仍需进一步研究。
[Abstract]:Objective: to study the expression of miR-146a,miR-155 and Ets-1,IRAK1 in peripheral blood mononuclear cells (peripheral blood mononuclear cells,PBMCs) and inflammatory factors in plasma of patients with rheumatoid arthritis (rheumatoid arthiritis,RA). At the same time, the relationship between the above factors and the condition of RA was analyzed, and the role of these factors in the pathogenesis of RA was preliminarily discussed. Methods: from September 2015 to May 2016, 44 RA patients, including 6 males and 38 females, were enrolled in the Department of traditional Chinese Medicine of Southern Hospital. According to the degree of disease activity, 23 patients were divided into high activity group (4 males and 19 females) and low activity group (21 patients), including 2 males and 19 females. All patients with RA met the RA classification criteria as revised by the American Rheumatology Society (ACR) and the European Union against Rheumatism (EULAR) in 2010. The healthy control group consisted of 22 patients, including 6 males and 16 females, who were examined in the Department of physical examination of Southern Hospital in the same period. There was no significant difference in age and sex composition between the two groups. Real-time fluorescence quantitative polymerase reaction (RT-PCR) was used to detect the relative expression of miR-146a,miR-155 and Ets-1,IRAK1 mRNA in isolated PBMCs, while ELISA was used to detect the protein levels of Ets-1 and IRAK1 and TNF- 伪 in plasma. The levels of IL-1 尾, IL-2,IL-6,IL-17,IL-21 and DAS28,CRP,ESR,RF, anti CCP,Hb, total complement were analyzed. T test, nonparametric test, single factor analysis of variance and Pearson,Spearman correlation analysis were used in statistical processing. Results: the relative expression level of miR-146a,miR-155 in PBMCs of RA patients was significantly higher than that of healthy control group (P0.05), and the expression level of miR-146a,miR-155 in high activity group was significantly higher than that in low activity group (P0.05). There was no statistical difference between the low activity group and the healthy control group (P0.05). The relative expression level of PBMCs in RA patients was not significantly higher than that in healthy control group (P0.05), but the relative expression level in high activity group was significantly lower than that in low activity group and healthy control group (P0.05). There was no significant difference between the low activity group and the healthy control group (P0.05). The relative expression of IRAK1mRNA in RA group was significantly lower than that in healthy control group (P0.05), high activity group was significantly lower than healthy control group (P0.01), low activity group was significantly lower than healthy control group (P0.05). However, there was no significant difference between the high activity group and the low activity group (P0.05). There was no significant difference in the expression of Ets-1,IRAKI protein between the high activity group and the low activity group. There was no significant difference between the high activity group and the low activity group in the expression of TNF- 伪, IL-1 尾 (P0.05). ELISA). The expression of IL-6,IL-21 protein was increased in the plasma of RA patients, but IL-2,IL-17 did not change in the plasma of RA patients and healthy controls. Correlation analysis showed that the expression level of miR-155 was positively correlated with erythrocyte sedimentation rate (r = 0.319), negatively correlated with Hb (r = 0.386), Ets-1 was negatively correlated with CRP (r = 0.408, P < 0. 007), and was negatively correlated with Hb (r = 0. 386, P < 0. 007), Ets-1 was negatively correlated with CRP (r = 0. 408, P < 0. 007). There was a negative correlation between IRAK1 and total complement of RF,DAS28, (r ~ 0.513 ~ P ~ (0.001) ~ 0. 001 ~ 0. 332 ~ 0. 029 ~ 0. 49 ~ 0. 09 ~ 0. 015). Conclusion: this study found that the relative expression of miR-146a,miR155 in PBMCs was increased in RA patients, suggesting that miR146a,miR155 is involved in the pathogenesis of RA and may be a diagnostic marker of high activity of RA. The relative expression of Ets-1,IRAK1 was decreased, which may be involved in the regulation of RA. The expression of TNF- 伪 IL-1 尾 and IL-6,IL-21 inflammatory factors in plasma of RA patients was significantly increased, which may play an important role in the pathogenesis of RA. TNF- 伪, IL-6 were positively correlated with CRP,ESR,CRP. The judgement of disease activity has certain reference significance. Due to the limited sample size of this study, the relationship between miR-146a,miR1 55 and Ets-1,IRAK1 in the pathogenesis of RA and the changes of inflammatory factors need to be confirmed in a large number of subsequent studies, and the related regulatory mechanisms need to be further studied.
【学位授予单位】：南方医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R593.22
本文编号：2402924
[Abstract]:Objective: to study the expression of miR-146a,miR-155 and Ets-1,IRAK1 in peripheral blood mononuclear cells (peripheral blood mononuclear cells,PBMCs) and inflammatory factors in plasma of patients with rheumatoid arthritis (rheumatoid arthiritis,RA). At the same time, the relationship between the above factors and the condition of RA was analyzed, and the role of these factors in the pathogenesis of RA was preliminarily discussed. Methods: from September 2015 to May 2016, 44 RA patients, including 6 males and 38 females, were enrolled in the Department of traditional Chinese Medicine of Southern Hospital. According to the degree of disease activity, 23 patients were divided into high activity group (4 males and 19 females) and low activity group (21 patients), including 2 males and 19 females. All patients with RA met the RA classification criteria as revised by the American Rheumatology Society (ACR) and the European Union against Rheumatism (EULAR) in 2010. The healthy control group consisted of 22 patients, including 6 males and 16 females, who were examined in the Department of physical examination of Southern Hospital in the same period. There was no significant difference in age and sex composition between the two groups. Real-time fluorescence quantitative polymerase reaction (RT-PCR) was used to detect the relative expression of miR-146a,miR-155 and Ets-1,IRAK1 mRNA in isolated PBMCs, while ELISA was used to detect the protein levels of Ets-1 and IRAK1 and TNF- 伪 in plasma. The levels of IL-1 尾, IL-2,IL-6,IL-17,IL-21 and DAS28,CRP,ESR,RF, anti CCP,Hb, total complement were analyzed. T test, nonparametric test, single factor analysis of variance and Pearson,Spearman correlation analysis were used in statistical processing. Results: the relative expression level of miR-146a,miR-155 in PBMCs of RA patients was significantly higher than that of healthy control group (P0.05), and the expression level of miR-146a,miR-155 in high activity group was significantly higher than that in low activity group (P0.05). There was no statistical difference between the low activity group and the healthy control group (P0.05). The relative expression level of PBMCs in RA patients was not significantly higher than that in healthy control group (P0.05), but the relative expression level in high activity group was significantly lower than that in low activity group and healthy control group (P0.05). There was no significant difference between the low activity group and the healthy control group (P0.05). The relative expression of IRAK1mRNA in RA group was significantly lower than that in healthy control group (P0.05), high activity group was significantly lower than healthy control group (P0.01), low activity group was significantly lower than healthy control group (P0.05). However, there was no significant difference between the high activity group and the low activity group (P0.05). There was no significant difference in the expression of Ets-1,IRAKI protein between the high activity group and the low activity group. There was no significant difference between the high activity group and the low activity group in the expression of TNF- 伪, IL-1 尾 (P0.05). ELISA). The expression of IL-6,IL-21 protein was increased in the plasma of RA patients, but IL-2,IL-17 did not change in the plasma of RA patients and healthy controls. Correlation analysis showed that the expression level of miR-155 was positively correlated with erythrocyte sedimentation rate (r = 0.319), negatively correlated with Hb (r = 0.386), Ets-1 was negatively correlated with CRP (r = 0.408, P < 0. 007), and was negatively correlated with Hb (r = 0. 386, P < 0. 007), Ets-1 was negatively correlated with CRP (r = 0. 408, P < 0. 007). There was a negative correlation between IRAK1 and total complement of RF,DAS28, (r ~ 0.513 ~ P ~ (0.001) ~ 0. 001 ~ 0. 332 ~ 0. 029 ~ 0. 49 ~ 0. 09 ~ 0. 015). Conclusion: this study found that the relative expression of miR-146a,miR155 in PBMCs was increased in RA patients, suggesting that miR146a,miR155 is involved in the pathogenesis of RA and may be a diagnostic marker of high activity of RA. The relative expression of Ets-1,IRAK1 was decreased, which may be involved in the regulation of RA. The expression of TNF- 伪 IL-1 尾 and IL-6,IL-21 inflammatory factors in plasma of RA patients was significantly increased, which may play an important role in the pathogenesis of RA. TNF- 伪, IL-6 were positively correlated with CRP,ESR,CRP. The judgement of disease activity has certain reference significance. Due to the limited sample size of this study, the relationship between miR-146a,miR1 55 and Ets-1,IRAK1 in the pathogenesis of RA and the changes of inflammatory factors need to be confirmed in a large number of subsequent studies, and the related regulatory mechanisms need to be further studied.
【学位授予单位】：南方医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R593.22
【参考文献】
相关期刊论文 前6条
1 尹志华;罗秀霞;张春容;陈新鹏;黄进贤;叶志中;;微小RNA-155通过抑制Ets-1促进Th17分化[J];中华风湿病学杂志;2015年11期
2 Izabela Korczowska;;Rheumatoid arthritis susceptibility genes: An overview[J];World Journal of Orthopedics;2014年04期
3 马倩;李向培;陶金辉;厉小梅;汪国生;钱龙;项楠;任启洁;何孝亮;方璇;;系统性红斑狼疮患者Ets-1表达及其调控微小RNAs的研究[J];中华风湿病学杂志;2013年12期
4 曾小峰;朱松林;谭爱春;谢小平;;我国类风湿关节炎疾病负担和生存质量研究的系统评价[J];中国循证医学杂志;2013年03期
5 张晓苹;李茹;王世瑶;穆荣;刘燕鹰;慈春增;栗占国;;微小RNA-146a对类风湿关节炎患者滑膜成纤维细胞抑制作用的研究[J];中华风湿病学杂志;2010年04期
6 ;2006年第二次全国残疾人抽样调查主要数据公报[J];中国康复理论与实践;2006年12期
相关硕士学位论文 前1条
1 戴超;SLE患者CD4+T细胞中miR326与Ets-1表达水平与Th17细胞比例的相关性研究及临床意义[D];安徽医科大学;2016年
，本文编号：2402924
本文链接：https://www.wllwen.com/yixuelunwen/nfm/2402924.html
最近更新
教材专著
