重型血友病A患儿关节出血后IL—1β、IL—6、TNF—α释放与关节病变形成的相关性研究(1)
[摘要] 目的 探讨重型血友病A患儿关节出血后IL-1β、IL-6、TNF-α释放与关节病变形成的相关性。方法 方便选取该院(2015年1月—2017年1月)收治的重型血友病A患儿60例，无关节出血组(n=20)，关节出血组(n=36)，急性关节出血组(n=20)，慢性关节出血组(n=15)，应用酶联免疫吸附实验测定血清TNF-α、IL-6、IL-1β水平。 结果 急性关节出血组关节病变患者细胞內TNF-α信使核糖核酸表达水平(6.695±2.523)ng/L，明显高于无关节病变患者(1.791±1.479)ng/L，差异有统计学意义(t=4.934 6，P<0.05)；急性关节出血组关节病变细胞内IL-6、IL-1β信使核糖核酸表达水平分别为(0.912±0.525)ng/L、(1.879±1.542)ng/L；无关节病变者分别为(1.263±0.647)ng/L、(0.971 8±0.517)ng/L，急性关节出血组关节病变与无关节病变细胞内IL-6、IL-1β信使核糖核酸表达水平对比差异无统计学意义(t=1.336 2、1.592 9，P>0.05)。结论 重型血友病A患儿急性关节出血TNF-α、IL-6、IL-1β水平明显升高，以TNF-α表达水平最高，且伴关节病变患儿TNF-α水平也明显升高，因此关节病变形成的关键因子为TNF-α。
[关键词] 重型血友病A；急性关节出血；TNF-α；IL-6；IL-1β；关节病变
[中图分类号] R4 [文献标识码] A [文章编号] 1674-0742(2019)03(a)-0013-03
[Abstract] Objective To investigate the relationship between the release of IL-1β， IL-6 and TNF-α and the formation of joint lesions in children with severe hemophilia A. Methods 60 patients with severe hemophilia A admitted to our hospital (January 2015 to January 2017)， no joint bleeding group (n=20)， joint bleeding group (n=36)， acute joint bleeding group were selected (n=20)， chronic joint bleeding group (n=15)， serum TNF-α， IL-6， IL-1β levels were determined by enzyme-linked immunosorbent assay. Results The expression level of TNF-α messenger ribonucleic acid in patients with acute joint hemorrhage was (6.695±2.523)ng/L， which was significantly higher than that of patients without joint disease (1.791±1.479)ng/L. The difference was statistically significant (t=4.934 6， P<0.05)； acute joint expression levels of IL-6 and IL-1β messenger RNA in the joints of the hemorrhagic group were (0.912±0.525)ng/L and (1.879±1.542)ng/L， respectively. The patients without joint lesions were (1.263±0.647)ng/L and (0.971 8±0.517)ng/L， respectively. There was no significant difference in the expression levels of IL-6 and IL-1β messenger RNA in articular lesions (t=1.336 2， 1.592 9， P>0.05). Conclusion The levels of TNF-α， IL-6 and IL-1β in patients with severe hemophilia A are significantly increased， and the expression level of TNF-α is the highest， and the level of TNF-α is also significantly increased in children with joint disease. Therefore， the key factor for the formation of joint lesions is TNF-α.
[Key words] Severe hemophilia A； Acute joint bleeding； TNF-α； IL-6； IL-1β； Joint disease
血友病A为一种先天性出血性疾病，主要原因为缺乏凝血因子Ⅷ，统计显示，每年发病率为0.02%[1]。虽然随着医学技术的发展，血友病的治疗效果有了极大的提高，但血友病关节出血后第一合并症关节病变并没有得到有效的预防和治疗，导致患者出现炎症甚至残疾[2]。虽然世界血友病联盟推荐预防治疗，但该预防治疗也仅能降低出血时间的发生几率，若患者形成了关节病，就不能再逆转，因此预防治疗效果不全面[3]。有学者研究显示，同样的出血情况下，关节病形成存在个体差异，这提示血友病关节病的形成不仅与关节出血有关，还存在其他因素[4]。血液充满关节腔后激活基质金属蛋白酶类、肿瘤坏死因子-α(TNF-α)、单核/巨噬系统释放白细胞介素-1β(IL-1β)，致使血管内皮生长因子增加，形成滑膜炎性反应，出血后滑膜内铁沉积损害软骨细胞，导致关节出现功能障碍或退行性变，这个过程与风湿性关节很相似[5]。目前在风湿免疫病领域中，已经发现了炎性反应因子与关节炎的关系，特别是TNF-α、白介素-6(IL-6)、IL-1β，且抗TNF-α、IL-6、IL-1β的靶向药物也已广泛运用于慢性关节病变预防[6]。虽然目前知道TNF-α、IL-6、IL-1β与血友病关节病变有密切关系，但其形成过程中的作用如何还不清楚，本研究选取我院(2015年1月—2017年1月)收治的重型血友病A患儿60例，就探讨重型血友病A患儿关节出血后IL-1β、IL-6、TNF-α释放与关节病变形成的相关性。, http://www.100md.com(周娟)
[关键词] 重型血友病A；急性关节出血；TNF-α；IL-6；IL-1β；关节病变
[中图分类号] R4 [文献标识码] A [文章编号] 1674-0742(2019)03(a)-0013-03
[Abstract] Objective To investigate the relationship between the release of IL-1β， IL-6 and TNF-α and the formation of joint lesions in children with severe hemophilia A. Methods 60 patients with severe hemophilia A admitted to our hospital (January 2015 to January 2017)， no joint bleeding group (n=20)， joint bleeding group (n=36)， acute joint bleeding group were selected (n=20)， chronic joint bleeding group (n=15)， serum TNF-α， IL-6， IL-1β levels were determined by enzyme-linked immunosorbent assay. Results The expression level of TNF-α messenger ribonucleic acid in patients with acute joint hemorrhage was (6.695±2.523)ng/L， which was significantly higher than that of patients without joint disease (1.791±1.479)ng/L. The difference was statistically significant (t=4.934 6， P<0.05)； acute joint expression levels of IL-6 and IL-1β messenger RNA in the joints of the hemorrhagic group were (0.912±0.525)ng/L and (1.879±1.542)ng/L， respectively. The patients without joint lesions were (1.263±0.647)ng/L and (0.971 8±0.517)ng/L， respectively. There was no significant difference in the expression levels of IL-6 and IL-1β messenger RNA in articular lesions (t=1.336 2， 1.592 9， P>0.05). Conclusion The levels of TNF-α， IL-6 and IL-1β in patients with severe hemophilia A are significantly increased， and the expression level of TNF-α is the highest， and the level of TNF-α is also significantly increased in children with joint disease. Therefore， the key factor for the formation of joint lesions is TNF-α.
[Key words] Severe hemophilia A； Acute joint bleeding； TNF-α； IL-6； IL-1β； Joint disease
血友病A为一种先天性出血性疾病，主要原因为缺乏凝血因子Ⅷ，统计显示，每年发病率为0.02%[1]。虽然随着医学技术的发展，血友病的治疗效果有了极大的提高，但血友病关节出血后第一合并症关节病变并没有得到有效的预防和治疗，导致患者出现炎症甚至残疾[2]。虽然世界血友病联盟推荐预防治疗，但该预防治疗也仅能降低出血时间的发生几率，若患者形成了关节病，就不能再逆转，因此预防治疗效果不全面[3]。有学者研究显示，同样的出血情况下，关节病形成存在个体差异，这提示血友病关节病的形成不仅与关节出血有关，还存在其他因素[4]。血液充满关节腔后激活基质金属蛋白酶类、肿瘤坏死因子-α(TNF-α)、单核/巨噬系统释放白细胞介素-1β(IL-1β)，致使血管内皮生长因子增加，形成滑膜炎性反应，出血后滑膜内铁沉积损害软骨细胞，导致关节出现功能障碍或退行性变，这个过程与风湿性关节很相似[5]。目前在风湿免疫病领域中，已经发现了炎性反应因子与关节炎的关系，特别是TNF-α、白介素-6(IL-6)、IL-1β，且抗TNF-α、IL-6、IL-1β的靶向药物也已广泛运用于慢性关节病变预防[6]。虽然目前知道TNF-α、IL-6、IL-1β与血友病关节病变有密切关系，但其形成过程中的作用如何还不清楚，本研究选取我院(2015年1月—2017年1月)收治的重型血友病A患儿60例，就探讨重型血友病A患儿关节出血后IL-1β、IL-6、TNF-α释放与关节病变形成的相关性。, http://www.100md.com(周娟)