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哮喘患儿血清VEGF、MMP-9及TIMP-1含量变化和意义

发布时间:2018-11-04 16:29
【摘要】:目的:支气管哮喘(bronchial asthma)简称哮喘,是儿童时期最常见的慢性呼吸道疾病。哮喘是由多种细胞和细胞组分共同参与的气道慢性炎症性疾病,这种慢性炎症导致气道反应性的增高,出现广泛多变的可逆性气流受限,,并引起反复发作的喘息、气促、胸闷或咳嗽等症状,并多在夜间和(或)清晨发作或加剧,重者可发生哮喘持续状态而危及生命,严重影响了患儿的身心健康。哮喘的发病机制极为复杂,与免疫、神经、精神、内分泌因素和遗传学背景密切相关。其主要的病理生理机制是气道炎症和气道重塑。而气道重塑情况对哮喘患儿的远期预后起着更重要的作用。基质金属蛋白酶-9(Matrix Metalloproteinase-9,MMP-9)和金属蛋白酶组织抑制剂-1(Tissue inhibitor of metalloproteinase-1,TIMP-1)的失衡是哮喘气道重塑的重要理论,血管形成是哮喘患者气道重塑的先决条件,而血管内皮生长因(Vascular endothelial growth factor,VEGF)是血管新生最重要的正调控因子。本研究通过监测MMP-9、TIMP-1及VEGF在哮喘患者不同时期的动态变化,探讨其在支气管哮喘发病中的机制和作用,为临床诊治提供新的理论依据和实验室证据,评价治疗效果,并为支气管哮喘开辟新的治疗途径。 方法:随机选取2011年2月---2012年1月就诊于河北医科大学第二医院和沧州市人民医院儿科门诊及入住病房的支气管哮喘患儿63例作为研究对象,根据其病史及临床表现分为哮喘急性发作期和临床缓解期两组,所有研究对象诊断标准均符合中华医学会儿科学分会呼吸学组2008年制定的《儿童支气管哮喘诊断与防治指南》中关于儿童支气管哮喘的诊断标准,并剔除近一个月内口服或静脉使用过糖皮质激素或免疫调节剂的,第一次喘息发作的及哮喘合并其他免疫性疾病如幼年类风湿性关节炎、结核病、系统性红斑狼疮等患儿。其中哮喘急性发作期38例,临床缓解期25例。另随机选取同时期同年龄组25例健康体检儿童作为对照,对照组儿童均无过敏性疾病病史及免疫相关性疾病病史及家族史,近期(1个月内)无全身感染性疾病,未使用抗生素与糖皮质激素、抗组胺药物。各组间在性别、年龄上均无明显差异(P0.05)。采用酶联免疫双抗体夹心(ELISA)法测定各组儿童血清中MMP-9、TIMP-1及VEGF的水平。所得数据采用SPSS13.0软件进行统计学处理。统计学方法采用方差分析、直线回归相关分析,以P0.05为显著性界限。 结果: 1血清MMP-9水平(ng/ml):急性发作期组为516.18±186.81;临床缓解期组为251.95±58.67;正常对照组为79.29±26.09。三组间比较差异有显著性(P0.05)。急性发作期和临床缓解期高于正常对照,有统计学意义(P0.05);急性发作期高于临床缓解期,有统计学意义(P0.05)。 2血清TIMP-1水平(ng/ml):急性发作期组为139.04±49.91;临床缓解期组为97.64±36.54;正常对照组为78.10±32.11。三组间比较差异有显著性(P0.05)。急性发作期高于临床缓解期和正常对照,有统计学意义(P0.05;临床缓解期与正常对照间无统计学意义(P0.05)。 3血清VEGF水平(pg/ml):急性发作期组为341.73±19.32;临床缓解期组为141.80±18.66;正常对照组为41.12±13.96。三组间比较差异有显著性(P0.05)。急性发作期和临床缓解期高于正常对照,有统计学意义(P0.05);急性发作期高于临床缓解期,有统计学意义(P0.05)。 4血清MMP-9/TIMP-1:急性发作期组为:3.74±0.28;临床缓解期组为:2.85±1.04;正常对照组为:1.07±0.16。三组间比较差异有显著性(P0.05)。急性发作期和临床缓解期高于正常对照,有统计学意义(P0.05);急性发作期高于临床缓解期,有统计学意义(P0.05)。 5哮喘儿童血清急性发作期MMP-9与VEGF之间呈直线正相关关系,相关系数r=0.358(P0.05),直线回归方程为Y=322.59+0.037X。 结论: 1哮喘患儿血清VEGF水平增高,参与了哮喘气道重塑。 2血清VEGF水平在缓解期患儿中明显低于发作期患儿,积极有效的治疗可减轻气道重塑。 3哮喘患儿血清MMP-9、TIMP-1的水平及二者比例增高,参与了气道重塑过程。
[Abstract]:Objective: Asthma is the most common chronic respiratory disease in childhood. asthma is an airway chronic inflammatory disease that is co-administered by a plurality of cells and cell components, which results in an increase in airway reactivity, a wide variety of reversible airflow limitations, and symptoms such as wheezing, shortness of breath, chest distress, or cough, and at night and/ or early in the morning or exacerbates, the heavy person can cause the persistent state of the asthma to endanger the life, and seriously affect the physical and mental health of the child. The pathogenesis of asthma is very complex, which is closely related to immunity, nerve, spirit, endocrine factor and genetic background. Its main pathological characteristics are airway inflammation and airway remodeling. And airway remodeling plays a more important role in the long-term prognosis of children with asthma. The imbalance of matrix metalloproteinase-9 (MMP-9) and metalloprotease tissue inhibitor-1 (TIMP-1) is an important theory of airway remodeling in asthma. VEGF) is the most important positive regulator of angiogenesis. By monitoring the dynamic changes of MMP-9, TIMP-1 and VEGF in different periods of asthma patients, the mechanism and role of MMP-9, TIMP-1 and VEGF in the pathogenesis of bronchial asthma were discussed, and new theoretical basis and laboratory evidence were provided for clinical diagnosis and treatment. Methods: From February 2011 to January 2012, 63 children with bronchial asthma were selected from the Second Affiliated Hospital of Hebei Medical University and Cangzhou People's Hospital. Subjects were divided into asthma acute attack period and clinical remission stage according to their medical history and clinical manifestations. Both groups, all the diagnostic criteria of the study subjects met the guidelines for the diagnosis and control of bronchial asthma in children, formulated in 2008 by the Respiratory Society of the Chinese Medical Association's Academy of Pediatrics, and the diagnosis of bronchial asthma in children. Patients with asthma and other immunological diseases, such as juvenile rheumatoid arthritis, tuberculosis, systemic lupus erythematosus, etc., for the first time of wheezing and other immunological diseases, such as juvenile rheumatoid arthritis, tuberculosis, systemic lupus erythematosus, etc. The acute episode of asthma in 38 patients, the clinical remission stage 2 In 5 cases, 25 healthy children in the same age group were randomly selected as control group. The control group had no history of allergic disease history and history of immune-related diseases and family history. In the near term (within 1 month), there were no systemic infectious diseases, antibiotics and glucocorticoid, antihistamines were not used. There was no significant difference in sex and age (P0.05). 5) Determination of MMP-9, TIMP-1 and VEGF in serum of children by enzyme-linked immunosorbent assay (ELISA) Level. The obtained data were statistics using SPSS 13.0 software Statistical methods were analyzed by variance analysis and linear regression analysis. Limits. Results: The level of MMP-9 in serum (ng/ ml): the acute attack period was 516. 18 and 186. 81; the clinical remission stage group was 251. 95 65.58. 67; the normal control group was 79. 29. 26. 09. There was significant difference between the three groups The acute attack period and the clinical remission stage were higher than that in the normal control group (P 0.05). The acute attack period was higher than the clinical remission stage. The serum TIMP-1 level (ng/ ml): the acute attack stage group was 139.04/ 49.91; the clinical remission stage group was 97. 64, 36. 54; the normal control group was 78. 10 110.32. 11. Comparison of three groups There was a significant difference (P0.05). The acute attack period was higher than the clinical remission stage and the normal control, there was statistical significance (P0.05). (p0.05). Serum VEGF level (pg/ ml): The acute attack period was 341. 73 and 19. 32; the clinical remission stage group was 141. 80 72.18. 66; normal. The ratio between the three groups was 41. 12 and 13.96. The difference was significant (P0.05). The acute attack period and clinical remission stage were higher than that of normal control (P0.05). There was statistical significance (P0.05). Serum MMP-9/ TIMP-1: The acute attack period was 3.74 Mt. 0. 28; the clinical remission stage group was 2.85% 1.04. The normal control group was 1. 07, 0. 16. 3. There was a significant difference between the groups (P0.05). The acute attack period and the clinical remission stage were higher than that of the normal control group (P 0.05). There was a positive correlation between MMP-9 and VEGF in children with asthma, and the correlation coefficient r = 0.358 (P0.05). regress Cheng is Y = 322. 59 + 0. 037X. Conclusion: Serum VEGF levels increased in children with asthma, and were involved in airway remodeling in asthmatic children. The positive and effective treatment can relieve airway remodeling in children who are obviously lower than those in the stage of onset, and the serum of children with asthma can be treated with positive and effective treatment.
【学位授予单位】:河北医科大学
【学位级别】:硕士
【学位授予年份】:2012
【分类号】:R725.6

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