類風濕關節(jié)炎患者外周血miR-146a、miR-155與Ets-1、IRAK1的表達及臨床意義
發(fā)布時間：2019-01-06 14:35
【摘要】：目的:研究類風濕關節(jié)炎(rheumatoid arthiritis,RA)患者外周血單個核細胞(peripheral blood mononuclear cells,PBMCs)中 miR-146a、miR-155 與 Ets-1、IRAK1和血漿中炎癥因子的表達水平,同時結合臨床指標分析以上因子及與RA病情的相關性,初步探討上述幾種因子在RA發(fā)病過程中的作用。方法:收集2015年9月至2016年5月在南方醫(yī)院中醫(yī)科住院RA患者44例,其中男性6例,女性38例。根據患者的病情活動度分為高活動組23例,其中男性4例,女性19例;低活動組21例,其中男性2例,女性19例。所有RA患者均符合2010年美國風濕學會(ACR)聯(lián)合歐洲抗風濕聯(lián)盟(EULAR)修訂的RA分類標準。健康對照組為同期在南方醫(yī)院體檢科的體檢者22例,其中男性6例,女性16例。兩組在年齡及性別構成方面的差異無統(tǒng)計學意義。采用實時熒光定量聚合酶反應(RT-PCR)檢測分離的PBMCs中的miR-146a、miR-155及Ets-1、IRAK1 mRNA的相對表達水平,同時ELISA檢測血漿中Ets-1和IRAK1的蛋白水平,檢測血漿中TNF-α、IL-1β、IL-2、IL-6、IL-17、IL-21 的水平,并與DAS28、CRP、ESR、RF、抗CCP、Hb、總補體等進行相關性分析。統(tǒng)計學處理采用t檢驗,非參數檢驗,單因素方差分析,Pearson、Spearman相關分析,以P0.05為差異有統(tǒng)計學意義。結果:miR-146a、miR-155在RA患者PBMCs中的相對表達水平顯著高于健康對照組(P0.05),高活動組的表達水平明顯高于低活動組(P0.05)、低活動組和健康對照組比較未發(fā)現(xiàn)統(tǒng)計學差異(P0.05);RA患者PBMCs的Ets-1 mRNA相對表達水平與健康對照組無統(tǒng)計學意義(P0.05),但高活動組中的相對表達水平顯著低于低活動組和健康對照組(P0.05),低活動組與健康對照組無統(tǒng)計學差異(P0.05);RA患者中的IRAK1mRNA相對表達水平明顯低于健康對照組(P0.05),高活動組顯著低于健康對照組(P0.01)、低活動組顯著低于健康對照組(P0.05),而高活動組與低活動組之間未發(fā)現(xiàn)有統(tǒng)計學差異(P0.05)。Ets-1、IRAKI在RA血漿中的蛋白表達水平與健康對照者無統(tǒng)計學差異(P0.05)。ELISA檢測發(fā)現(xiàn)TNF-α、IL-1β、IL-6、IL-21的蛋白表達水平在RA患者血漿中表達增高的,而IL-2、IL-17在RA患者與健康對照者的血漿中無明顯變化。相關性分析顯示miR-155的表達水平與血沉正相關(r=0.319,P=0.042),與 Hb 成負相關(r=-0.386,PP=0.017);Ets-1 與 CRP負相關(r=-0.408,P,P=0.007);IRAK1 與 RF、DAS28、總補體負相關(r=-0.513,P=0.001;r=-0.332,P=0.029;r=-0.49,P=0.015)。結論:此次研究發(fā)現(xiàn)RA患者PBMCs的miR-146a、miR155相對表達水平增高,提示miR146a、miR155參與RA的發(fā)病,可能成為RA高活動的診斷標志物;Ets-1、IRAK1相對表達水平降低,可能參與RA的調控;RA患者血漿中TNF-α IL-1β、IL-6、IL-21炎癥因子表達明顯增高,可能在RA發(fā)病中扮演重要角色,TNF-α、IL-6與CRP、ESR、CRP呈正相關,對病情活動的判斷有一定的參考意義。由于本研究樣本量有限,miR-146a、miR1 55和Ets-1、IRAK1參與RA發(fā)病的關系及炎癥因子的變化有待后續(xù)大樣本研究證實,其相關調控機制仍需進一步研究。
[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- 偽 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- 偽, 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- 偽 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- 偽, 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.
【學位授予單位】：南方醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R593.22
本文編號：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- 偽 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- 偽, 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- 偽 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- 偽, 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.
【學位授予單位】：南方醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R593.22
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