益肺活血汤对大鼠慢性阻塞性肺疾病模型肺组织氧化抗氧化失衡的影响

Effect of Yifei Huoxue soup on the lung tissue oxidant/antioxidant imbalance in COPD rats

关键词:  益肺活血汤  慢性阻塞性肺疾病  氧化应激  氧化抗氧化失衡  大鼠

Key words:  Yifei Huoxue soup  COPD  oxidant stress  oxidant  antioxidant imbalance  rat

摘要:

[目的] 观察益肺活血汤对大鼠慢性阻塞性肺疾病（COPD）模型病理和肺功能的影响，评价其在氧化/抗氧化失衡机制方面的干预效应。[方法] 采用SPF级雄性SD大鼠40只随机分为对照组10只、COPD组15只、益肺活血汤组15只。COPD组采用气管内注射脂多糖联合香烟烟雾吸入法制备大鼠COPD模型同时给予生理盐水灌胃。益肺活血汤组在COPD组制备方法基础上同时给予益肺活血汤灌胃治疗。对照组则采用室内环境喂养，气管内注射液生理盐水，同时给予生理盐水灌胃。模型制备及治疗过程结束后检测各组大鼠肺功能，并检测肺组织中谷胱甘肽（GSH）、丙二醛（MDA）和超氧化物歧化酶（SOD）含量，转录因子红细胞系-2p45（NF-E2）相关因子-2（Nrf2）和γ-谷氨酰半胱氨酸合成酶（γ-GCS）蛋白及mRNA表达。[结果] 与对照组比较，模型组肺功能及肺组织病理切片提示COPD模型制备成功，MDA、GSH增高，SOD下降，NRF2和γ-GCS的蛋白及mRNA表达增高。与模型组比较，治疗组肺功能和肺组织病理变化减轻，MDA、GSH下降，SOD增高，NRF2和γ-GCS的蛋白及mRNA表达下降。[结论] 益肺活血汤能有效减轻气管内注射脂多糖联合香烟烟雾吸入所造成的大鼠肺功能下降和肺组织病理变化。其机制应与通过提高肺组织SOD的含量从而减轻氧化应激有关，与激活Keap1-Nrf2-ARE通路引起γ-GCS基因和蛋白水平上调、GSH增多相关可能性小。

Abstract:

[Objective] The aim of this study is to evaluate the effect of Yifei Huoxue soup (YFHXS) intervention on pathology, pulmonary function, oxidative stress and antioxidant status of COPD rats.[Methods] Forty SPF-grade male Sprague-Dawley rats were randomly divided into the control group (n=10), the COPD model group (n=15) and the YFHXS group (n=15). The COPD rat model was established by exposure to cigarettes smoke plus intratracheal injecting of lipopolysaccharide (LPS) and administered with physiological saline by gastro gavage. YFHXS group was established in the same way as COPD model group and administered with YFHXS by gastro gavage. The control group was administered with physiological saline by gastro gavage. After all medication, pulmonary function was measured by testing FEV_0.3, FEV_0.3/FVC and PEF. Morphological changes of the lung tissue were observed under microscope after H&E staining. The level of MDA, SOD and GSH were detected to estimate the oxidative stress level in rat lungs. The expression of Nrf2 and γ-GCS in the lung tissue were also detected.[Results] The difference between pulmonary function and pathology in COPD group with in control group indicated that the COPD model was made up successfully. In contrast with the control group, the COPD group had a significant increase in MDA and GSH, where as there was a significant decrease in SOD levels. The γ-GCS and Nrf2 both in mRNA and protein levels were also detected higher in COPD group than in control group. In comparison with COPD group, YFHXS was effective to increase pulmonary function and improve lung pathological impairment. YFHXS treatment decreased MDA and GSH, while improved SOD levels. The γ-GCS and Nrf2 both in mRNA and protein levels were also detected decreased in YFHXS group than in COPD group. [Conclusion] YFHXS was effective to improve pulmonary function and lung pathological impairment which were caused by exposing to smoke plus LPS. YFHXS showed antioxidative capacity by improving SOD levels. However, it was unlikely that the antioxidative effect of YFHXS was associated with activation of Keap1-Nrf2-ARE pathway and increase of γ-GCS and GSH levels.