原发性胆汁性肝硬化患者外周血IL-8及其受体CXCR1、CXCR2的表达及临床意义  

Expressions and clinical significances of IL-8 and its receptors( CXCR1/2) in peripheral blood from the patients with primary biliary cirrhosis

作　　者：杨敏[1] 黄凤楼[1] 傅海涛[1] 秦保东[1] 姚定康[2] 杨再兴[1] 仲人前[1] 

机构地区：[1]第二军医大学长征医院实验诊断科,上海200003 [2]第二军医大学长征医院消化科,上海200003

出　　处：《临床检验杂志》2014年第5期362-365,共4页Chinese Journal of Clinical Laboratory Science

基　　金：国家自然科学基金(81072479);卫生部卫生公益性行业科研专项(201202004)

摘　　要：目的探讨原发性胆汁性肝硬化(PBC)患者血浆白介素-8(IL-8)和外周血单个核细胞(PBMC)中IL-8、白介素-8受体1(CXCR1)、白介素-8受体2(CXCR2)、G蛋白耦联受体激酶5(G protein-coupled receptor kinase 5,GRK5)的表达变化及其临床意义。方法用实时荧光定量PCR(qRT-PCR)法检测25例PBC患者和25例健康人对照组PBMCs中IL-8、CXCR1、CXCR2、GRK5的mRNA水平,western blot检测CXCR1、CXCR2蛋白表达水平,ELISA法检测血浆IL-8的含量,连续监测法测定血清碱性磷酸酶(ALP)、γ-谷氨酰基转移酶(GGT)含量,并对各指标进行相关性分析。结果 PBC组血浆中IL-8浓度[(73.43±13.24)pg/mL]明显高于对照组[(34.76±10.12)pg/mL](P<0.01)。PBC组IL-8、CXCR1、CXCR2、GRK5的mRNA相对表达水平[M(P25,P75)]为2.17(0.96,2.84)、1.71(0.97,3.26)、1.64(0.95,2.56)、1.86(1.34,2.30),高于对照组的0.99(0.48,1.35)、0.99(0.39,1.24)、1.06(0.56,1.32)、0.99(0.53,1.28),差异有统计学意义(P均<0.05)。western blot结果提示,CXCR1、CXCR2的蛋白质水平也较对照组升高。PBC组血清ALP活性为128.0(99.5,164.5)IU/mL,对照组为51.0(42.3,62.0)IU/mL,P<0.01;PBC组GGT活性为85.0(43.5,138.0)IU/mL,对照组为14.0(12.0,16.8)IU/mL,P<0.01。PBMC中IL-8 mRNA表达水平与CXCR1存在正相关,相关系数(r)=0.420,P<0.05;CXCR1与CXCR2呈正相关(r=0.441,P<0.05);CXCR2与GRK5呈正相关(r=0.515,P<0.01);血清ALP与GGT呈正相关(r=0.702,P<0.01),其他指标之间无相关关系。结论 PBC患者外周血IL-8及其受体水平升高,推测IL-8及其受体信号转导过程可能在PBC的发病过程中起重要作用,为PBC的免疫干预治疗途径提供新的方向,但其与PBC的严重程度并无明显相关关系。Objective To investigate the expression levels of IL-8 in plasma,and IL-8,its receptors（ CXCR1 /CXCR2） and G protein-coupled receptor kinase 5（ GRK5） in peripheral blood mononuclear cells（ PBMC） from the patients with primary biliary cirrhosis（ PBC） and their clinical significances. Methods The mRNA levels of IL-8,CXCR1,CXCR2 and GRK5 and the protein levels of CXCR1 and CXCR2 in PBMCs from 25 PBC patients and 25 health controls were detected by quantitative real time polymerase chain reaction（ qRT-PCR） and Western blot,respectively. The levels of IL-8 in plasma and ALP and GGT in serum were determined by ELISA and continuous monitoring method,respectively. Then,the correlations between these markers were analyzed. Results Plasma IL-8 concentration in PBC patients [（ 73. 43 ± 13. 24） pg / mL] was significantly higher than that in the controls [（ 34. 76 ± 10. 12） pg /mL） ]（ P〈0. 01）. Similarly,the mRNA levels [M（ P25,P75） ]of IL-8 [2. 17（ 0. 96,2. 84） vs 0. 99（ 0. 48,1. 35） ],CXCR1 [1. 71（ 0. 97,3. 26） vs 0. 99（ 0. 39,1. 24） ],CXCR2 [1. 64（ 0. 95,2. 56） vs 1. 06（ 0. 56,1. 32） ]and GRK5 [1. 86（ 1. 34, 2. 30） vs 0. 99（ 0. 53,1. 28） ]in PBC patients were also significantly higher than those in the controls（ P〈0. 05）. Western blot demonstrated that the protein levels of CXCR1 and CXCR2 also increased in PBC patients. In addition,the activities [M（ P25,P75） ]of serum ALP [128. 0（ 99. 5,164. 5） IU / mL vs 51. 0（ 42. 3,62. 0） IU / mL] and GGT [85. 0（ 43. 5,138. 0） IU / mL vs 14. 0（ 12. 0, 16. 8） IU / mL]in PBC patients were significantly higher than those in the controls（ P〈0. 01）. There was no any correlation between these markers except positive correlations between IL-8 and CXCR1（ r = 0. 420,P〈0. 05）,between CXCR1 and CXCR2（ r = 0. 441, P〈0. 05）,between CXCR2 and GRK5（ r = 0. 515,P〈0. 01）,and between ALP and GGT（ r = 0. 702,P〈0. 01）. Conclusion The expression levels of IL-8 and its receptors

关 键 词：原发性胆汁性肝硬化 白介素-8 白介素-8受体1 2 G蛋白耦联受体激酶5 

分 类 号：R392.3[医药卫生—免疫学]