乌苯美司对慢性阻塞性肺疾病小鼠免疫失衡及氧化应激的影响

Effect of Ubenimex on Immune Imbalance and Oxidative Stress in Mice with Chronic Obstructive Pulmonary Disease

关键词:  慢性阻塞性肺疾病  乌苯美司  免疫功能  氧化应激  小鼠

Key words:  chronic obstructive pulmonary disease  ubenimex  immune function  oxidative stress  mouse

摘要:

目的 研究乌苯美司对慢性阻塞性肺疾病（chronic obstructive pulmonary disease，COPD）小鼠免疫失衡及氧化应激的影响。方法 50只小鼠随机分为空白组、模型组、乌苯美司组、氨茶碱+吸氧组、氨茶碱+吸氧+乌苯美司组，共5组。空白组不做处理，其余4组均诱导建立COPD小鼠模型，造模第8天开始，乌苯美司组以20 mg·kg^-1乌苯美司灌胃治疗；氨茶碱+吸氧组采用吸氧、氨茶碱溶液（10 mL·kg^-1）灌胃常规治疗；氨茶碱+吸氧+乌苯美司组在氨茶碱+吸氧组基础上加以20 mg·kg^-1灌胃乌苯美司治疗；空白组、模型组予以同等剂量的生理盐水，连续给药4周，采用Buxco系统检测小鼠肺功能吸气峰流量（peak inspiratory flow，PIF）、呼气峰流量（peak expiratory flow，PEF）、每分钟通气量（minute volume，MV）后处死小鼠，采血样及肺组织样本。HE染色考察肺组织病理学变化；流式细胞测定全血CD3⁺、CD4⁺、CD8⁺水平，并计算CD4⁺/CD8⁺；ELISA检测血清MDA、SOD、IL-8、TNF-α、CRP水平。结果 与模型组相比，乌苯美司组、氨茶碱+吸氧组、氨茶碱+吸氧+乌苯美司组病理损伤明显减轻；氨茶碱+吸氧+乌苯美司组PIF、PEF、MV及CD3⁺、CD4⁺、CD4⁺/CD8⁺水平明显升高（P<0.01），CD8⁺水平明显降低（P<0.05）；仅氨茶碱+吸氧+乌苯美司组较模型组MDA、SOD、TNF-α、IL-8、CRP含量均明显改善（P<0.01）。结论 乌苯美司辅助常规治疗能有效改善COPD小鼠肺功能及免疫水平，减轻炎症反应和调节氧化应激，促进肺组织明显恢复。

Abstract:

OBJECTIVE To study the effects of ubenimex on immune imbalance and oxidative stress in mice with chronic obstructive pulmonary disease(COPD). METHODS Fifty mice were randomly divided into 5 groups:blank group, model group, ubenimex group, aminophylline+oxygen group, aminophylline+oxygen+ubenimex group. The blank group was not treated, and the other four groups were induced mice model of COPD. On the 8th day of modeling, ubenimex group was treated with 20 mg·kg^-1 ubenimex; aminophylline+oxygen group was treated with oxygen and aminophylline solution(10 mL·kg^-1); aminophylline+oxygen+ubenimex group was treated with 20 mg·kg^-1 of ubenimex on the basis of aminophylline+oxygen group; the blank group and model group were given the same dose of normal saline, continuous administration for 4 weeks. Lung function of peak inspiratory flow(PIF), peak expiratory flow(PEF), minute volume(MV) were detected by Buxco system and then the mice were sacrificed for collecting blood samples and lung tissue samples. HE staining was used to investigate the pathological changes of lung tissue; flow cytometry to determine CD3⁺, CD4⁺, CD8⁺ levels in blood, and calculate CD4⁺/CD8⁺; serum MDA, SOD, IL-8, TNF-α, and CRP levels were measured by ELISA. RESULTS Compared with model group, the pathological damage in ubenimex group, aminophylline+oxygen group and aminophylline+oxygen+ubenimex group were significantly reduced(P<0.01). PIF, PEF, MV and CD3⁺, CD4⁺, CD4⁺/CD8⁺ levels of aminophylline+oxygen+ubenimex group were significantly increased(P<0.01), while the CD8⁺ level were significantly decreased(P<0.05). The contents of MDA, SOD, TNF-α, IL-8 and CRP only in aminophylline+oxygen+ubenimex group were all significantly improved compared with model group(P<0.01). CONCLUSION Ubenimex adjuvant therapy can effectively improve lung function and immune level in COPD mice, reduce inflammation and regulate oxidative stress and promote the recovery of lung tissue in COPD mice.