间歇低氧合并肺气肿大鼠模型肝脏氧化应激及凝血功能的研究

摘要

Objective To establish the rat overlap syndrome (OS) model of intermittent hypoxia (IH) combined with pulmonary emphysema and to explore its connection with hepatic oxidative stress, inflammatory status in the live and coagu⁃lation profile. Methods Male Wistar rats (n=60) were randomly divided into four groups:control group (A), IH group (B), pulmonary emphysema group (C) and OS group (D). The rat model of pulmonary emphysema was established by exposing rats in smoke for 16 weeks. From the 13th week, pre-programmed intermittent hypoxia/re-oxygenation (IH/ROX) exposure was given in the meantime of smoke exposure in OS group. Liver tissues were sectioned or triturated for pathological scoring or for detecting expression levels of superoxide dismutase (SOD), catalase (CAT) and malondialdehyde (MDA) respectively. Se⁃rum levels of coagulant/anticoagulant factors such as antithrombin (AT), fibrinogen (FIB), von Willebrand factor(vWF) and FactorⅧ(FⅧ) were also evaluated using biochemistry analysis. Results The levels of pathological scores and coagulant factors(FIB, FⅧ:C and vWF:Ag)were significantly higher in group D than those in group A, B and C. The values of SOD, CAT and AT were significantly lower in group D than those in other three groups. Serum levels of FIB, vWF:Ag, FⅧ:C and AT:A correlated with SOD(r equal to-0.905、-0.941、-0.946 and 0.817 respective,P<0.01). Conclusion In rat overlap syndrome when IH combined with pulmonary emphysema, hepatic inflammation and coagulability present mutual promotion effect and produce a more significant liver-derivative inflammatory and prothrombotic status.%目的：建立肺气肿合并间歇低氧（IH）的重叠综合征（OS）大鼠模型，探讨OS大鼠肝脏炎性损伤及其凝血功能的变化。方法将60只雄性Wistar大鼠随机分成正常组（A组）、IH组（B组）、肺气肿组（C组）和IH合并肺气肿组（D组）。通过对大鼠进行16周的熏烟暴露造成大鼠肺气肿；从13周开始，同时施加程控预制的间歇低氧/再氧合（IH/ROX）处理对大鼠进行IH暴露4周。暴露结束后取各组大鼠肺和肝脏组织于光镜下观察并计算肝脏炎性损伤病理评分。取肝组织匀浆采用ELISA方法测定其超氧化物歧化酶（SOD）活性、过氧化氢酶（CAT）活性和丙二醛（MDA）浓度。检测血浆纤维蛋白原（FIB），血浆因子FⅧ促凝活性（FⅧ：C）、血管性血友病因子抗原（vWF：Ag）和抗凝血酶活性（AT：A）水平。结果 D组肝脏炎性损伤病理评分和凝血因子FIB、FⅧ：C、vWF：Ag水平均高于A、B、C组，而SOD和CAT活性以及AT：A水平低于其他3组（均P<0.05）。FIB、vWF：Ag、FⅧ：C、AT：A与SOD呈明显相关（r分别为-0.905、-0.941、-0.946和0.817，均P<0.01）。结论 OS动物模型下IH和肺气肿在导致氧化应激和高凝状态上具有一定叠加效应，可引起更强的肝脏炎症反应和血栓前状态。