哮喘患兒血清VEGF、MMP-9及TIMP-1含量變化和意義
發(fā)布時間：2018-11-04 16:29
【摘要】：目的：支氣管哮喘（bronchial asthma）簡稱哮喘，是兒童時期最常見的慢性呼吸道疾病。哮喘是由多種細(xì)胞和細(xì)胞組分共同參與的氣道慢性炎癥性疾病，這種慢性炎癥導(dǎo)致氣道反應(yīng)性的增高，出現(xiàn)廣泛多變的可逆性氣流受限，，并引起反復(fù)發(fā)作的喘息、氣促、胸悶或咳嗽等癥狀，并多在夜間和（或）清晨發(fā)作或加劇，重者可發(fā)生哮喘持續(xù)狀態(tài)而危及生命，嚴(yán)重影響了患兒的身心健康。哮喘的發(fā)病機(jī)制極為復(fù)雜，與免疫、神經(jīng)、精神、內(nèi)分泌因素和遺傳學(xué)背景密切相關(guān)。其主要的病理生理機(jī)制是氣道炎癥和氣道重塑。而氣道重塑情況對哮喘患兒的遠(yuǎn)期預(yù)后起著更重要的作用。基質(zhì)金屬蛋白酶-9（Matrix Metalloproteinase-9，MMP-9）和金屬蛋白酶組織抑制劑-1（Tissue inhibitor of metalloproteinase-1，TIMP-1）的失衡是哮喘氣道重塑的重要理論，血管形成是哮喘患者氣道重塑的先決條件，而血管內(nèi)皮生長因（Vascular endothelial growth factor，VEGF）是血管新生最重要的正調(diào)控因子。本研究通過監(jiān)測MMP-9、TIMP-1及VEGF在哮喘患者不同時期的動態(tài)變化，探討其在支氣管哮喘發(fā)病中的機(jī)制和作用，為臨床診治提供新的理論依據(jù)和實(shí)驗(yàn)室證據(jù)，評價治療效果，并為支氣管哮喘開辟新的治療途徑。 方法：隨機(jī)選取2011年2月---2012年1月就診于河北醫(yī)科大學(xué)第二醫(yī)院和滄州市人民醫(yī)院兒科門診及入住病房的支氣管哮喘患兒63例作為研究對象，根據(jù)其病史及臨床表現(xiàn)分為哮喘急性發(fā)作期和臨床緩解期兩組，所有研究對象診斷標(biāo)準(zhǔn)均符合中華醫(yī)學(xué)會兒科學(xué)分會呼吸學(xué)組2008年制定的《兒童支氣管哮喘診斷與防治指南》中關(guān)于兒童支氣管哮喘的診斷標(biāo)準(zhǔn)，并剔除近一個月內(nèi)口服或靜脈使用過糖皮質(zhì)激素或免疫調(diào)節(jié)劑的，第一次喘息發(fā)作的及哮喘合并其他免疫性疾病如幼年類風(fēng)濕性關(guān)節(jié)炎、結(jié)核病、系統(tǒng)性紅斑狼瘡等患兒。其中哮喘急性發(fā)作期38例，臨床緩解期25例。另隨機(jī)選取同時期同年齡組25例健康體檢兒童作為對照，對照組兒童均無過敏性疾病病史及免疫相關(guān)性疾病病史及家族史，近期（1個月內(nèi)）無全身感染性疾病，未使用抗生素與糖皮質(zhì)激素、抗組胺藥物。各組間在性別、年齡上均無明顯差異（P0.05）。采用酶聯(lián)免疫雙抗體夾心（ELISA）法測定各組兒童血清中MMP-9、TIMP-1及VEGF的水平。所得數(shù)據(jù)采用SPSS13.0軟件進(jìn)行統(tǒng)計學(xué)處理。統(tǒng)計學(xué)方法采用方差分析、直線回歸相關(guān)分析，以P0.05為顯著性界限。 結(jié)果： 1血清MMP-9水平（ng/ml）：急性發(fā)作期組為516.18±186.81；臨床緩解期組為251.95±58.67；正常對照組為79.29±26.09。三組間比較差異有顯著性（P0.05）。急性發(fā)作期和臨床緩解期高于正常對照,有統(tǒng)計學(xué)意義（P0.05）；急性發(fā)作期高于臨床緩解期，有統(tǒng)計學(xué)意義（P0.05）。 2血清TIMP-1水平（ng/ml）：急性發(fā)作期組為139.04±49.91；臨床緩解期組為97.64±36.54；正常對照組為78.10±32.11。三組間比較差異有顯著性（P0.05）。急性發(fā)作期高于臨床緩解期和正常對照，有統(tǒng)計學(xué)意義（P0.05；臨床緩解期與正常對照間無統(tǒng)計學(xué)意義(P0.05)。 3血清VEGF水平（pg/ml）：急性發(fā)作期組為341.73±19.32；臨床緩解期組為141.80±18.66；正常對照組為41.12±13.96。三組間比較差異有顯著性（P0.05）。急性發(fā)作期和臨床緩解期高于正常對照,有統(tǒng)計學(xué)意義（P0.05）；急性發(fā)作期高于臨床緩解期，有統(tǒng)計學(xué)意義（P0.05）。 4血清MMP-9/TIMP-1：急性發(fā)作期組為：3.74±0.28；臨床緩解期組為：2.85±1.04；正常對照組為：1.07±0.16。三組間比較差異有顯著性（P0.05）。急性發(fā)作期和臨床緩解期高于正常對照，有統(tǒng)計學(xué)意義（P0.05）；急性發(fā)作期高于臨床緩解期，有統(tǒng)計學(xué)意義（P0.05）。 5哮喘兒童血清急性發(fā)作期MMP-9與VEGF之間呈直線正相關(guān)關(guān)系，相關(guān)系數(shù)r=0.358（P0.05）,直線回歸方程為Y=322.59+0.037X。 結(jié)論： 1哮喘患兒血清VEGF水平增高,參與了哮喘氣道重塑。 2血清VEGF水平在緩解期患兒中明顯低于發(fā)作期患兒，積極有效的治療可減輕氣道重塑。 3哮喘患兒血清MMP-9、TIMP-1的水平及二者比例增高,參與了氣道重塑過程。
[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.
【學(xué)位授予單位】：河北醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2012
【分類號】：R725.6
本文編號：2310448
[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.
【學(xué)位授予單位】：河北醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2012
【分類號】：R725.6
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