基于动物模型文献的慢性阻塞性肺疾病与其客观指标的关联性分析

Relationship between objective markers and chronic obstructive pulmonary disease in animal models:a review of literature

目的:通过研究烟熏加气管内滴入脂多糖法建立慢性阻塞性肺疾病(COPD)的动物模型文献,对COPD模型与文献中出现的客观指标进行数理分析,探索COPD与客观指标的关联性,为揭示COPD的发病机制及疗效评价提供思路和方法。方法:以中国学术期刊全文数据库(CNKI)、中文科技期刊数据库(维普、VIP)、万方数据库和中国生物医学文献数据库为数据源,以"慢性阻塞性肺疾病"、"COPD"、"动物"、"鼠"为检索词检索相关文献,数据预处理后,运用"比值法"和"积分法"两种数学方法进行数据分析,并进行等级排序。结果:对纳入的合格文献156篇中的60项客观指标进行数理分析,结果显示:气道阻力(R)、呼气阻力(Re)、吸气阻力(Ri)、二氧化碳分压(PaCO2)、平均肺动脉压(MPAP)、气道炎症病理评分、腺体厚度/气管壁厚度(Reid指数)、羟脯氨酸(Hy)、平均肺泡面积、气管壁厚度、平滑肌面积、肺平均内衬间隔、透明质酸、上皮层面积、层粘连蛋白、中性粒细胞、细胞总数、淋巴细胞、转化生长因子-β2、转化生长因子-β1、碱性成纤维细胞生长因子、表皮生长因子、细胞间黏附分子-1、核因子-κB、白介素-6、巨噬细胞炎症蛋白-2、白介素-8、核因子相关因子2、活性氧浓度、γ-谷氨酰半胱氨酸合成酶活性、丙二醛、过氧化物酶、基质金属酶-2、基质金属酶-9、金属蛋白酶组织抑制因子-1的比值,│P│值(或│Q│值)较大且P值(或Q值)为正值;白介素-10的比值,│P│值(或│Q│值)较大且P值(或Q值)为负值。0.3s用力呼气容积占用力肺活量百分比(FEV0.3/FVC)、用力肺活量(FVC)、血氧饱和度(SaO2)、右心室/左心室+室间隔重量比值、巨噬细胞等指标│P│值(或│Q│值)较小。结论:COPD模型与R、Re、Ri、PaCO2、MPAP等指标关联性较强,而与FEV0.3/FVC、FVC、SaO2等指标表现出较弱的相关性。本研究为基于该模型而评价疗效或探讨机制提供依据。

Objective： To study the animal model [a combination of tobacco smoke（TS） and lipopolysaccharide（LPS）] of chronic obstructive pulmonary disease（COPD） and analyze the relationship between COPD and its objective markers by mathematical method from literature, to providing new insights into COPD pathogenesis and therapeutic evaluation. Methods： Based on the database of China National Knowledge Infrastructure Database（CNKI）, Chongqing VIP Chinese Science and Technology Periodical Database（VIP）, Wan fang Data and Chinese Biomedical Literature Database（CBM）, using ＇chronic obstructive pulmonary disease＇ , ＇COPD＇ , ＇animal＇ , ＇rat＇ as mesh term, we searched literature of animal experiments and analyzed objective data using ＂ratio-comparison＂ and ＂integration-comparison＂ methods. Results： 156 literatures（involving 60 objective indicators） were included and analyzed by mathematical methods, those results showed that airway resistance（R）, expiratory resistance（Re）, inspiration resistance（Ri）, PaCO2, MPAP, pathological score of airway inflammation, the ratio of mean thickness of glands and airway wall, hydroxyproline, average pulmonary alveoli area, mean thickness of airway wall, area of bronchial smooth muscle （WArn）, pulmonary mean linear intercept（MLI）, hyaluronic acid（HA）, area of epidermis, laminin（LN）, neutrophils, the total number of cells, Lymphocyte, TGF- β 2, TGF- β 1, BFGF, EGF, ICAM-1, NF-κB, IL-6, MIP-2, IL-8, Nrf2, concentration of reactive oxygen species, γ-glutamylcysteine synthetase（GCS） activity, malondialdehyde（MDA）, peroxidase （POD）, MMP-2, MMP-9, TIMP-1 had great IPI （or laD values and positive [P] （or/QI）, IL-10 had great Iel （or [Q]） values and negative IPI （or IQ[）. FEV0.flFVC, FVC, SaO2, the ratio of fight ventricular and left ventricle plus interventricular septum, macrophages had small [P[ （or [Q[）values. Conclusion： There are strong correlation between the animal model of COPD and R, Re, Ri, PaCO2, MPAP, etc, however, FEV0JFVC, FVC, SaO2 and other indicators show less importance for COPD. The outcome will provides some new idea for pathogenesis researching and therapeutic evaluating.