摘要
目的探索重型血友病A患儿关节出血后炎性反应因子白细胞介素-1β(interleukin-1β,IL-1β)、白细胞介素-6(interleukin-6,IL-6)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)在形成关节病变中的作用,为进一步开展血友病关节病变防控提供理论依据。方法收集2015年10月至2016年4月于首都医科大学附属北京儿童医院血友病门诊就诊、符合入组条件的血友病A患儿,记录患儿关节出血情况,根据患儿关节出血情况进行分组:无关节出血(non-joint bleeding,NJB)组和关节出血(joint bleeding,JB)组,后者包括急性关节出血(acute joint bleeding,AJB)组与慢性关节出血(chronic joint bleeding,CJB)组,留取外周静脉血标本,用酶联免疫吸附实验(enzyme-linked immunosorbent assay,ELISA)检测血清中IL-1β、IL-6及TNF-α的表达水平,用反转录-聚合酶链反应(reverse transcription-polymerase chain reaction,RT-PCR)检测细胞内IL-1β、IL-6、TNF-α的mRNA表达水平,收集实验数据并进行统计学分析。结果共入组患儿47例,其中无关节出血组17例、急性关节出血组17例(有关节病变者8例,无关节病变者9例)、慢性关节出血组13例,入组患儿中位年龄5.5(2~18)岁。急性关节出血组、慢性关节出血组与无关节出血组的TNF-α的细胞内mRNA的水平差异有统计学意义(P<0.05),且急性关节出血组、慢性关节出血组的TNF-α的细胞内mRNA的水平均高于无关节出血组(P<0.05)。急性关节出血组伴关节病变与急性关节出血组不伴关节病变的TNF-α的细胞内mRNA的水平(5.584±3.634 vs 1.680±1.590)差异有统计学意义(P=0.02)。结论重型血友病A患儿关节出血急性期IL-1β、IL-6、TNF-α表达升高,以TNF-α升高为主,慢性期只见TNF-α表达升高,伴有关节病变的患儿TNF-α表达水平明显升高,故TNF-α是关节病变形成的关键因子。
Objective To explore the role of inflammatory factors [interleukin-1β( IL-1β),interleukin-6( IL-6),tumor necrosis factor-α( TNF-α) ] in the formation of haemophilic arthropathy in children with severe hemophilia A,and to provide theoretical basis for further prevention and treatment target of hemophilia joint disease. Methods The eligibility hemophilia A children were enrolled from the Hemophilia Outpatient Clinic of Beijing Children Hospital during 2015-2016. Patients were divided into non-joint bleeding( NJB) group,joint bleeding( JB) group [acute joint bleeding( AJB) group,chronic joint bleeding( CJB) group]. Peripheral venous blood was collected,the expression of IL-1β, IL-6 and TNF-α in blood serum were detected by enzyme-linked immunosorbent assay( enzyme-linked immunosorbent assay,ELISA). The expression of mRNA of IL-1β,IL-6 and TNF-α was detected by reverse transcription-polymerase chain reaction( RT-PCR). Statistical analysis the levels of IL-1β,IL-6 and TNF-α in blood serum and their mRNA expression. Results A total of 47 cases were collected in the patients group,including 17 cases of NJB group,17 cases of AJB group( 8 cases with target joint,9 cases without target joint) and 13 cases of CJB group. Median age was 5. 5 years( 2 years to18 years). There was significant difference in the expression of mRNA of TNF-α between NJB group,JB group and AJB group( P < 0. 05). There was significant difference in the expression of mRNA of TNF-α between AJB group with arthropathy( n = 8,5. 584 ± 3. 634) and AJB group without arthropathy( n = 9,1. 680 ± 1. 590)( P = 0. 02). Conclusion The expression of IL-1β,IL-6 and TNF-α in children with hemophilia increased in acute joint bleeding,and the expression of TNF-α increased mainly in acute,chronic and with haemophilic arthropathy,so TNF-α is the key of cytokines in the formation of haemophilic arthropathy in children with severe hemophilia A.
引文
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