胰岛素生长因子及组织蛋白酶B在慢性阻塞性肺疾病患者血液中的表达及临床意义

发布时间：2018-03-31 23:35

  本文选题：慢性阻塞性肺疾病　切入点：胰岛素生长因子Ⅰ　出处：《山西医科大学》2013年硕士论文

【摘要】：研究目的 近些年来,慢性阻塞性肺疾病(Chronic obstructive pulmonary diseases, COPD)已经逐渐成为了一个十分重要的公共卫生问题,其主要原因包括患病人数剧增,死亡率居高不下,从而直接成为一个严重的社会经济负担。更好的了解COPD的分子学和细胞学的发病机制,可指导许多基础和临床的研究方向,从而改进早期诊断方法,寻求干预性靶向治疗,发现“易感”人群及治疗急性加重期患者。胰岛素生长因子(Insulin-like growth factor, IGF)由于其在细胞分化,细胞增殖以及细胞个体发育中都表现出十分重要的促进作用,所以具有重要的研究意义,而该因子本身是一类多功能细胞增殖调控因子。目前已经有关于IGF与生长、代谢、心脏、骨质疏松等多个领域的研究,但IGF作为气道的重塑因子,这方面的研究极少。由于IGF对细胞增殖和凋亡具有双重调节的功能,并且在临床上,多种慢性疾病及肿瘤多伴随IGF的异常,因此利用这一因子,发挥其在诊断和治疗中的独特价值变得由为重要。组织蛋白酶在蛋白降解中起重要作用,它还参与生长因子、血管增殖调节及协助其他细胞因子调节等,有助于细胞迁移、增殖及凋亡等的调节。组织蛋白酶B(Cathepsin B, CB)是半胱氨酸蛋白水解酶家族中的一员,其引起细胞外基质的降解也越来越得到人们的关注,目前在临床方面有组织蛋白酶与肿瘤、血管性疾病、肾疾病及骨骼疾病等的研究,有关组织蛋白酶B在肺部疾病的研究甚少。本实验通过对COPD患者血清中胰岛素生长因子-Ⅰ(IGF-Ⅰ)、胰岛素生长因子-Ⅱ(IGF-Ⅱ)及外周血单个核细胞中组织蛋白酶B的测定,可以了解这些因子及蛋白在人体内含量的变化及其三者之间的关系,从而对COPD早期诊断方法及干预性靶向治疗提供更多的内容。 材料和方法 在我院筛选79例COPD患者及40例健康对照者,抽取静脉血,应用ELISA方法测定了19例I级、20例II级、21例III级、19例IV级COPD患者和40例健康人血清中IGF-Ⅰ、IGF-Ⅱ的含量,应用Western blot检测所有研究对象外周血单个核细胞中组织蛋白酶B的含量,由定量数据分析其直线相关关系。 研究结果 与对照组相比,COPD组血清中IGF-Ⅰ、IGF-Ⅱ水平均明显升高(P0.05, P▲0.05); COPD患者血清中IGF-Ⅰ、IGF-Ⅱ水平随着疾病分级的增加而明显增加(P0.05,P*0.05)；组织蛋白酶B含量随着COPD分级的增加而明显降低,COPD组组织蛋白酶B的表达水平与血清中IGF-Ⅰ、IGF-Ⅱ的水平分别呈负相关(P0.01,P*0.01)。 结论 COPD患者血清中IGF-Ⅰ、IGF-Ⅱ含量升高,且随着疾病分级的增加而明显增加；COPD患者外周血单个核细胞中的组织蛋白酶B表达下降,且随COPD分级的增加而明显降低,组织蛋白酶B表达水平与IGF-Ⅰ、IGF-Ⅱ的含量分别呈负相关,组织蛋白酶B可能通过降解IGF结合蛋白蛋白酶发挥作用,从而间接降低IGF-Ⅰ、IGF-Ⅱ的含量。
[Abstract]:Research purposeChronic obstructive pulmonary disease (copd) has become an important public health problem in recent years, mainly due to the sharp increase in the number of people suffering from the disease and the high mortality rate.Thus directly become a serious social and economic burden.A better understanding of the molecular and cytological pathogenesis of COPD can guide many basic and clinical research directions, so as to improve the early diagnosis, seek intervention targeted therapy, and find the "susceptible" population and the treatment of acute exacerbation patients.Insulin-like growth factor (IGF) plays an important role in promoting cell differentiation, cell proliferation and cell ontogeny.And this factor itself is a kind of multifunctional cell proliferation regulation factor.At present, there have been many studies on IGF and growth, metabolism, heart, osteoporosis and so on. However, as airway remodeling factor, IGF is rarely studied.Because IGF has dual regulation function on cell proliferation and apoptosis, and many kinds of chronic diseases and tumors are accompanied by abnormal IGF in clinic, it is important to use this factor to play its unique value in diagnosis and treatment.Cathepsin plays an important role in protein degradation. It also participates in the regulation of growth factor, vascular proliferation and other cytokines, which is helpful to the regulation of cell migration, proliferation and apoptosis.Cathepsin B(Cathepsin B (CBB) is a member of the cysteine proteolytic enzyme family. The degradation of extracellular matrix (ECM) caused by cathepsin B (CBB) has attracted more and more attention.There are few studies on cathepsin B in lung diseases, such as kidney disease and bone disease.In this study, we measured the levels of serum IGF- 鈪，

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