摘要
目的探讨慢性阻塞性肺疾病(COPD)高凝状态的相关影响因素。方法采用脂多糖叠加烟熏法建立COPD大鼠模型,将SD大鼠随机分为COPD组和对照组,每组10只。检测肺总量(TLC)、功能残气量(FRC)、吸气阻力(RI)、200 ms用力呼气量与用力肺活量比值(FEV200/FVC)等肺功能指标,HE染色观察肺组织病理学改变,ELISA检测血浆中缺氧诱导因子-1α(HIF-1α)、EPO、血浆纤维蛋白原(FIB)、D二聚体(D-D)表达量,RT-qPCR检测肺组织中HIF-1α、EPO表达量,凝血分析仪检测凝血酶原时间(PT)、活化部分凝血酶原时间(APTT)表达量,血常规仪检测RBC、HGB表达量,并对HIF-1α、EPO、RBC、HGB与PT、APTT、FIB、D-D做相关性分析。结果COPD组大鼠TLC、FRC、RI均高于对照组,FEV200/FVC低于对照组(P均<0.05)。与对照组相比,COPD组大鼠肺组织HE染色显示肺气肿和慢性支气管炎改变。COPD组HIF-1α、EPO、RBC、HGB、FIB、D-D均高于对照组,PT、APTT均低于对照组(P均<0.05)。相关性分析显示,血浆EPO与血浆HIF-1α、D-D、全血RBC及HGB呈正相关,血浆HIF-1α与血浆FIB、D-D呈正相关,全血RBC、HGB与血浆D-D呈正相关(P均<0.05)。结论脂多糖叠加烟熏3个月造模,可建立符合人类COPD病理生理改变的大鼠模型。COPD大鼠高凝状态的发生与HIF-1α、EPO、RBC、HGB高表达相关。
Objective To explore the related factors of hypercoagulability in chronic obstructive pulmonary disease(COPD).Methods COPD rat model was established by lipopolysaccharide combined with smoking.SD rats were randomly divided into COPD group and control group with 10 rats in each group.The lung function indexes such as total lung capacity(TLC),functional residual capacity(FRC),airway resistance(RI),and FEV200/FVC were detected.HE staining was used to observe the pathological changes of lung tissue.The expression of HIF-1α,EPO,fibrinogen(FIB)and D-dimer(D-D)in plasma were detected by ELISA.The expression of HIF-1αand EPO in lung tissue were detected by RT-qPCR.The expression of prothrombin time(PT)and activated partial prothrombin time(APTT)were detected by coagulation analyzer.The expression of RBC and HGB was detected by blood routine analyzer.The correlation between HIF-1α,EPO,RBC,HGB and PT,APTT,FIB,D-D were analyzed.Results The levels of TLC,FRC and RI in COPD group were higher than those in control group,and FEV200/FVC in COPD group was lower than that in control group(P all<0.05).Compared with the control group,HE staining showed emphysema and chronic bronchitis in COPD group.The levels of HIF-1α,EPO,RBC,HGB,FIB and D-D in COPD group were higher than those in control group,while PT and APTT in COPD group were lower than those in control group(P<0.05).Correlation analysis showed that plasma EPO level was positively correlated with plasma HIF-1α,D-D,whole blood RBC and HGB levels,plasma HIF-1αlevel was positively correlated with Plasma FIB and D-D levels,and whole blood RBC and HGB levels was positively correlated with D-D level(P all>0.05).Conclusion Lipopolysaccharide combined with smoking for 3 months was used to establish a COPD rat model in accordance with the pathophysiological changes of human COPD.The occurrence of hypercoagulable state in COPD rats is related to the high expression of HIF-1α,EPO,RBC and HGB.
作者
武杰
张瑞
许旺
张少华
陈丽君
WU Jie;ZHANG Rui;XU Wang;ZHANG Shaohua;CHEN Lijun(Ningxia Medical University,Yinchuan 750004,China;Ningxia Key Laboratory of Cerebrocranial Diseases,Ningxia Medical University,Yinchuan 750004,China;Department of Respiratory and Critical Care Medicine,The Second Affiliated Hospital of Ningxia Medical University,Yinchuan 750001,China;Department of Pathology,The Second Affiliated Hospital of Ningxia Medical University,Yinchuan 750001,China)
出处
《宁夏医科大学学报》
2021年第6期603-607,613,共6页
Journal of Ningxia Medical University
基金
宁夏重点研发项目(2018BEG03077)。