类风湿关节炎患者膝关节滑膜组织中Sirt2和Sirt3 mRNA表达及意义
|
摘要
目的探讨类风湿关节炎(rheumatoid arthritis,RA)患者膝关节滑膜组织中Sirt2和Sirt3mRNA的表达情况及意义。方法行膝关节置换术的RA患者8例为RA组,行关节镜手术的半月板损伤患者6例为对照组,采用实时荧光定量PCR检测2组膝关节滑膜组织Sirt2、Sirt3mRNA表达水平,RA组患者检测抗环瓜氨酸多肽抗体、血沉、高敏C反应蛋白、类风湿因子水平,采用DAS28评分评估RA疾病活动度,采用Pearson相关性分析RA患者膝关节滑膜组织Sirt2、Sirt3mRNA表达水平与其临床检验指标间的相关性。结果 RA组膝关节滑膜组织Sirt2 mRNA表达水平(0.56±0.19)低于对照组(1.00±0.00),Sirt3mRNA表达水平(1.89±0.64)高于对照组(1.00±0.00)(P<0.05);RA患者抗环瓜氨酸多肽抗体水平为375.96(182.85,865.21)RU/mL,血沉47.00(28.25,68.25)mm/h,高敏C反应蛋白28.20(12.33,40.58)g/L,类风湿因子32.15(0,207.78)u/mL,DAS28评分4.18(3.52,4.69);RA患者膝关节滑膜组织Sirt3mRNA表达水平与抗环瓜氨酸多肽抗体呈正相关(r=0.770,P=0.025),与血沉、高敏C反应蛋白、DAS28评分、类风湿因子和病程无相关性(P>0.05),RA患者膝关节滑膜组织Sirt2mRNA表达水平与临床各指标均无明显相关性(P>0.05)。结论 RA患者膝关节滑膜组织中Sirt3mRNA表达增高,Sirt2mRNA表达降低;Sirt3可能与RA疾病预后相关。
Objective To explore the expressions and significances of Sirt2 and Sirt3 mRNA in synovial tissues of knee joint in patients with rheumatoid arthritis(RA).Methods The expressions of Sirt2 and Sirt3 mRNA in synovial tissues of knee joint were detected by real-time quantitative PCR in 8 patients with RA undergoing joint replacement(RA group)and 6 patients with menisici injuries undergoing arthroscopic surgery(control group).The levels of anti-cyclic peptide containing citrulline(anti-CCP)antibody,erythrocyte sedimentation rate(ESR),high-sensitivity C-reactive protein(hsCRP)and rheumatoid factor(RF)were detected in RA group.RA disease activity was analyzed by Disease Activity Score28(DAS28).The correlations of clinical indexes with Sirt2 and Sirt3 mRNA were analyzed by Pearson correlation method.Results The level of Sirt2 mRNA was significantly lower,and the level of Sirt3 mRNA was significantly higher in RA group(0.56±0.19,1.89±0.64)than that in control group(1.00±0.00,1.00±0.00)(P<0.05).In RA group,anti-CCP antibody was 375.96(182.85,865.21)RU/mL,ESR was 47.00(28.25,68.25)mm/h,hs-CRP was28.20(12.33,40.58)g/L,RF was 32.15(0,207.78)IU/mL and DAS28 was 4.18(3.52,4.69).The level of Sirt3 mRNA expression in RA group was positively correlated with anti-CCP antibody(r=0.770,P=0.025),and was not correlated with ESR,hs-CRP,DAS28,RF and disease duration(P>0.05).The level of Sirt2 mRNA was not correlated with all above clinical indexes(P>0.05).Conclusion Sirt3 mRNA expression increases and Sirt2 mRNA expression decreases in synovial tissues of knee joint in RA patients.The level of Sirt3 may be correlated with the prognosis of RA.
Objective To explore the expressions and significances of Sirt2 and Sirt3 mRNA in synovial tissues of knee joint in patients with rheumatoid arthritis(RA).Methods The expressions of Sirt2 and Sirt3 mRNA in synovial tissues of knee joint were detected by real-time quantitative PCR in 8 patients with RA undergoing joint replacement(RA group)and 6 patients with menisici injuries undergoing arthroscopic surgery(control group).The levels of anti-cyclic peptide containing citrulline(anti-CCP)antibody,erythrocyte sedimentation rate(ESR),high-sensitivity C-reactive protein(hsCRP)and rheumatoid factor(RF)were detected in RA group.RA disease activity was analyzed by Disease Activity Score28(DAS28).The correlations of clinical indexes with Sirt2 and Sirt3 mRNA were analyzed by Pearson correlation method.Results The level of Sirt2 mRNA was significantly lower,and the level of Sirt3 mRNA was significantly higher in RA group(0.56±0.19,1.89±0.64)than that in control group(1.00±0.00,1.00±0.00)(P<0.05).In RA group,anti-CCP antibody was 375.96(182.85,865.21)RU/mL,ESR was 47.00(28.25,68.25)mm/h,hs-CRP was28.20(12.33,40.58)g/L,RF was 32.15(0,207.78)IU/mL and DAS28 was 4.18(3.52,4.69).The level of Sirt3 mRNA expression in RA group was positively correlated with anti-CCP antibody(r=0.770,P=0.025),and was not correlated with ESR,hs-CRP,DAS28,RF and disease duration(P>0.05).The level of Sirt2 mRNA was not correlated with all above clinical indexes(P>0.05).Conclusion Sirt3 mRNA expression increases and Sirt2 mRNA expression decreases in synovial tissues of knee joint in RA patients.The level of Sirt3 may be correlated with the prognosis of RA.
引文
[1]LOPEZ-ARMADA M J,RIVEIRO-NAVEIRA R R,VAAMONDE-GARCA C,et al.Mitochondrial dysfunction and the inflammatory response[J].Mitochondrion,2013,13(2):106-118.
[2]CARAFA V,NEBBIOSO A,ALTUCCI L.Sirtuins and disease:the road ahead[J].Front Pharmacol,2012,3:1-6.
[3]VACHHARAJANI V T,LIU T,WANG X,et al.Sirtuins link inflammation and metabolism[J].J Immunol Res,2016:8167273.
[4]PLOUG D,GYSEMANS C,LUNDH M,et al.Lysine deacetylase inhibition prevents diabetes by chromatinindependent immunoregulation andβ-cell protection[J].Proc Natl Acad Sci USA,2014,111(3):1055-1059.
[5]ANDERSON R M,SHANMUGANAYAGAM D,WEINDRUCH R.Caloric restriction and aging:studies in mice and monkeys[J].Toxicol Pathol,2009,37(1):47-51.
[6]ANDERSON R M,WEINDRUCH R.The caloric restriction paradigm:implications for healthy human aging[J].Am J Hum Biol,2012,24(2):101-106.
[7]QIN W,CHACHICH M,LANE M,et al.Calorie restriction attenuates Alzheimers disease type brain amyloidosis in Squirrel monkeys(Saimiri sciureus)[J].J Alzheimers Dis,2006,10(4):417-422.
[8]SOMEYA S,YAMASOBA T,WEINDRUCH R,et al.Caloric restriction suppresses apoptotic cell death in the mammalian cochlea and leads to prevention of presbycusis[J].Neurobiol Aging,2007,28(10):1613-1622.
[9]ZENG L,YANG Y,HU Y,et al.Age-related decrease in the mitochondrial Sirtuin deacetylase Sirt3 expression associated with ROS accumulation in the auditory cortex of the mimetic aging rat model[J].PLoS One,2014,9(2):e88019.
[10]宋佳,杜引会,张巧娟,等.类风湿性关节炎肩关节高频超声评分与多项血清学指标的相关性分析[J].中华实用诊断与治疗杂志,2017,30(10):1011-1013.
[11]安乐美,楚天舒,刘谓,等.血清CXCL13在类风湿关节炎中的表达及意义[J].中华实用诊断与治疗杂志,2018,32(3):248-250.
[12]王露.雷公藤多苷联合甲氨蝶呤治疗类风湿性关节炎的临床疗效[J].中国实用医刊,2018,45(10):117-119.
[13]陈赵玲,刘岐焕,刘婧依,等.白芍总苷联合甲氨蝶呤治疗难治性类风湿关节炎效果观察[J].中华实用诊断与治疗杂志,2017,31(7):700-702.
[14]FEARON U,CANAVAN M,BINIECKA M,et al.Hypoxia,mitochondrial dysfunction and synovial invasiveness in rheumatoid arthritis[J].Nat Rev Rheumatol,2016,12(7):385-397.
[15]程兆明,王苏芹,庄禄昌,等.维生素E对骨性关节炎氧自由基水平的影响及意义[J].中国实用医刊,2018,45(1):17-19.
[16]BAUSE A S,HAIGIS M C.Sirt3regulation of mitochondrial oxidative stress[J].EXG,2013,48(7):634-639.
[17]YANG W,NAGASAWA K,MNCH C,et al.Mitochondrial Sirtuin network reveals dynamic Sirt3-dependent deacetylation in response to membrane depolarization[J].Cell,2017,167(4):985-1000.
[18]LIN J,SUN B,JIANG C,et al.Sirt2suppresses inflammatory responses in collagen-induced arthritis[J].Biochem Biophys Res Commun,2013,441(4):897-903.
[19]LEE H,KA S,LEE S,et al.Overexpression of Sirt6suppresses inflammatory responses and bone destruction in mice with collagen-induced arthritis[J].Arthritis Rheum,2013,65(7):1776-1785.
[20]PAIS T F,MARQUES O,MILLER-FLEMING L,et al.The NAD-dependent deacetylase Sirt2is a suppressor of microglial activation and brain in ammation[J].EMBO J,2013,32(19):2603-2616.
[21]ROTHGIESSER K M,ERENER S,WAIBEL S,et al.Sirt2regulates NF-κB dependent gene expression through deacetylation of p65 Lys310[J].J Cell Sci,2010,123(24):4251-4258.
[22]KARA M,YOLBAS S,SAHIN C,et al.Changes in Sirt2and Sirt3 mRNA expressions in rheumatoid arthritis[J].Eur JRheumatol,2017,4(2):83-86.
[2]CARAFA V,NEBBIOSO A,ALTUCCI L.Sirtuins and disease:the road ahead[J].Front Pharmacol,2012,3:1-6.
[3]VACHHARAJANI V T,LIU T,WANG X,et al.Sirtuins link inflammation and metabolism[J].J Immunol Res,2016:8167273.
[4]PLOUG D,GYSEMANS C,LUNDH M,et al.Lysine deacetylase inhibition prevents diabetes by chromatinindependent immunoregulation andβ-cell protection[J].Proc Natl Acad Sci USA,2014,111(3):1055-1059.
[5]ANDERSON R M,SHANMUGANAYAGAM D,WEINDRUCH R.Caloric restriction and aging:studies in mice and monkeys[J].Toxicol Pathol,2009,37(1):47-51.
[6]ANDERSON R M,WEINDRUCH R.The caloric restriction paradigm:implications for healthy human aging[J].Am J Hum Biol,2012,24(2):101-106.
[7]QIN W,CHACHICH M,LANE M,et al.Calorie restriction attenuates Alzheimers disease type brain amyloidosis in Squirrel monkeys(Saimiri sciureus)[J].J Alzheimers Dis,2006,10(4):417-422.
[8]SOMEYA S,YAMASOBA T,WEINDRUCH R,et al.Caloric restriction suppresses apoptotic cell death in the mammalian cochlea and leads to prevention of presbycusis[J].Neurobiol Aging,2007,28(10):1613-1622.
[9]ZENG L,YANG Y,HU Y,et al.Age-related decrease in the mitochondrial Sirtuin deacetylase Sirt3 expression associated with ROS accumulation in the auditory cortex of the mimetic aging rat model[J].PLoS One,2014,9(2):e88019.
[10]宋佳,杜引会,张巧娟,等.类风湿性关节炎肩关节高频超声评分与多项血清学指标的相关性分析[J].中华实用诊断与治疗杂志,2017,30(10):1011-1013.
[11]安乐美,楚天舒,刘谓,等.血清CXCL13在类风湿关节炎中的表达及意义[J].中华实用诊断与治疗杂志,2018,32(3):248-250.
[12]王露.雷公藤多苷联合甲氨蝶呤治疗类风湿性关节炎的临床疗效[J].中国实用医刊,2018,45(10):117-119.
[13]陈赵玲,刘岐焕,刘婧依,等.白芍总苷联合甲氨蝶呤治疗难治性类风湿关节炎效果观察[J].中华实用诊断与治疗杂志,2017,31(7):700-702.
[14]FEARON U,CANAVAN M,BINIECKA M,et al.Hypoxia,mitochondrial dysfunction and synovial invasiveness in rheumatoid arthritis[J].Nat Rev Rheumatol,2016,12(7):385-397.
[15]程兆明,王苏芹,庄禄昌,等.维生素E对骨性关节炎氧自由基水平的影响及意义[J].中国实用医刊,2018,45(1):17-19.
[16]BAUSE A S,HAIGIS M C.Sirt3regulation of mitochondrial oxidative stress[J].EXG,2013,48(7):634-639.
[17]YANG W,NAGASAWA K,MNCH C,et al.Mitochondrial Sirtuin network reveals dynamic Sirt3-dependent deacetylation in response to membrane depolarization[J].Cell,2017,167(4):985-1000.
[18]LIN J,SUN B,JIANG C,et al.Sirt2suppresses inflammatory responses in collagen-induced arthritis[J].Biochem Biophys Res Commun,2013,441(4):897-903.
[19]LEE H,KA S,LEE S,et al.Overexpression of Sirt6suppresses inflammatory responses and bone destruction in mice with collagen-induced arthritis[J].Arthritis Rheum,2013,65(7):1776-1785.
[20]PAIS T F,MARQUES O,MILLER-FLEMING L,et al.The NAD-dependent deacetylase Sirt2is a suppressor of microglial activation and brain in ammation[J].EMBO J,2013,32(19):2603-2616.
[21]ROTHGIESSER K M,ERENER S,WAIBEL S,et al.Sirt2regulates NF-κB dependent gene expression through deacetylation of p65 Lys310[J].J Cell Sci,2010,123(24):4251-4258.
[22]KARA M,YOLBAS S,SAHIN C,et al.Changes in Sirt2and Sirt3 mRNA expressions in rheumatoid arthritis[J].Eur JRheumatol,2017,4(2):83-86.