全真一气汤对COPD模型小鼠Nrf2通路及对炎性细胞因子和肺组织超微结构的影响

目的:研究全真一气汤对慢性阻塞性肺疾病(COPD)模型小鼠炎性细胞因子及肺组织超微结构的影响。方法:实验小鼠分为正常组、模型组、全真一气汤低、高剂量(4.3,8.6 g·kg-1)组、氨茶碱(2.3 mg·kg-1)组,采用熏香烟联合气道内细菌脂多糖(LPS)滴入法制作COPD稳定期小鼠模型,熏烟于16周结束。观察小鼠的一般情况,检测小鼠肺功能,计算肺泡灌洗液炎性细胞总数,肺组织白细胞介素-6(IL-6)和趋化因子(KC)表达量,免疫组化法检测肺组织细胞外调节蛋白激酶(ERK),核转录因子NF-E2相关因子(Nrf2),血红素加氧酶(HO-1)蛋白表达,透射电镜观察肺组织超微结构改变。结果:模型组小鼠一般状态较正常组差,全真一气汤低剂量组及高剂量组小鼠状态较模型组好转。与模型组比较,全真一气汤可降低COPD模型小鼠气道阻力(P0.05),降低肺静态顺应性(P0.05)和功能残气量;降低肺泡炎症细胞数(P0.05),降低炎症介质IL-6和KC表达量(P0.05),降低ERK和Nrf2蛋白表达量,增高HO-1蛋白表达量,肺组织电镜结果显示全真一气汤能减轻肺组织超微损害。结论:全真一气汤可改善COPD模型小鼠一般状态,减少炎症细胞因子表达,保护肺功能,减轻肺组织超微结构损害,能降低ERK和Nrf2蛋白表达量,上调HO-1蛋白表达,起到抗炎作用。

Effect of Quanzhen Yiqi Tang on Inflammatory Cytokines and Pulmonary Ultrastructure of Mice with Chronic Obstructive Pulmonary Disease

Objective: To study the effect of Quanzhen Yiqi Tang on inflammatory cytokines and pulmonary ultrastructure of mice with chronic obstructive pulmonary disease (COPD). Method: COPD mouse model were built by cigarette smoking and lipopolysaccharides(LPS) instillation in airway. They were divided into five groups, namely control group, model group, Quanzhen Yiqi Tang low-dose and high-dose groups (4.3, 8.6 g·kg^-1), and aminophylline group. After 16 weeks, lung function were tested, the total number of alveolar lavage inflammatory cells, expressions of lung tissue interleukin-6 (IL-6) and cutin chemotactic cytokines (KC) were counted. The immunohistochemistry method was used to detect extraeelluar regulated protein kinase(ERK), Nrf2 and heme oxygenase-1(HO-1) protein expressions. The lung tissue ultrastructure changes were observed by transmission electron microscope(TEM). Result: Compared with normal control group, Quanzhen Yiqi Tang low-dose group and high-dose group showed recovery in mice state. Compared with model group, Quanzhen Yiqi Tang reduced COPD airway resistance in model mice (P<0.05), the static lung compliance (P<0.05), functional residual capacity, the number of alveolar inflammatory cells (P<0.05), inflammation medium IL-6 (P<0.05) and KC (P<0.05) expression, Nrf2 and ERK protein expressions, and increased HO-1 protein expression. The electron microscope results showed that Quanzhen Yiqi Tang can reduce the lung tissue ultrastructural damage. Conclusion: Quanzhen Yiqi Tang could improve the general state of mice with COPD, reduce inflammatory cytokines, protect lung function, reduce the lung tissue ultrastructural damage and the amount of Nrf2 and ERK protein expression, and up-regulate HO-1 protein expression.