人参总皂苷在实验性肺纤维化小鼠中的抗氧化损伤作用

Antioxidative effect of total ginsenosides on exprimental pulmonary fibrosis of mice

目的探讨人参总皂苷(TG)对小鼠肺纤维化的保护作用,并初步探讨其作用机制。方法 60只昆明种小鼠随机分为假手术组、模型组、TG 40,80和160 mg·kg-1组及阳性药醋酸泼尼松5 mg·kg-1组。气管内灌注博来霉素(BLM)5 mg·kg-1建立肺纤维化小鼠模型。制模次日ig给药,每天1次,连续28 d,计算小鼠肺系数、HE染色及Masson染色观察肺组织病理形态改变、实时荧光定量PCR法检测α平滑肌肌动蛋白(α-SMA)m RNA的表达;试剂盒检测小鼠肺组织羟脯氨酸(HYP)、谷胱甘肽(GSH)含量、一氧化氮合酶(NOS)和髓过氧化物酶(MPO)活性、总抗氧化能力(T-AOC)和羟自由基(·OH)的水平。结果与假手术组比较,模型组小鼠肺系数显著升高(P<0.05),肺泡炎及肺纤维化明显,α-SMA m RNA的表达明显升高(P<0.01),小鼠肺组织HYP,·OH,NOS和MPO活性升高(P<0.05),但GSH和T-AOC水平下降(P<0.05);TG和醋酸泼尼松给药后能显著降低模型小鼠的肺系数(P<0.05),减轻肺纤维化程度;TG可使模型小鼠肺组织匀浆中·OH,NOS,MPO和HYP活性降低(P<0.05),GSH和T-AOC的水平显著升高(P<0.05)。结论 TG能改善博来霉素所致小鼠肺纤维化,其作用机制可能与其增加机体的抗氧化能力,减轻氧化损伤有关。

OBJECTIVE To observe the protective effect and underlying mechanism of total ginsenosides（TG） on bleomycin- induced pulmonary fibrosis. METHODS Intratracheal instillation of bleomycin 5 mg·kg^-1was conducted to establish a pulmonary fibrosis mouse model. Kunming mice（1/2males and 1/2 females）were randomly divided into sham-operation（Sham）,model,total ginsenosides 40,80 and 160 mg·kg^-1and prednisone acetate（5 mg·kg^-1） groups. After 28 d administration,the histopathological changes in the lung were analyzed by hematoxylin eosin（HE）and Masson staining.The exprssion of alpha smooth muscle actin（α-SMA）in the lung was detected by real-time PCR. The content of hydroxyproline（HYP）and glutathione（GSH）,level of total antioxidant capacity（T-AOC）and hydroxy radical（·OH）,activity of myeloperoxidase（MPO）and nitric oxide synthase（NOS）in the lung were detected by corresponding kits. RESULTS Compared with the sham group,the pulmonary indexes in model group were significantly increased（P〈0.01）,alveolitis and pulmonary fibrosis were obvious. The m RNA expression of α-SMA,content of HYP and ·OH,activity of MPO and NOS were increased（P〈0.05）,but the content of GSH and T- AOC in model group was decreased（P〈0.05）. Compared with model group,the pulmonary indexes in TG 80 and 160 mg·kg- 1and prednisone acetate 5 mg·kg- 1groups were reduced（P〈0.05）,and the degree of alveolitis and pulmonary fibrosis was mitigated. The m RNA expression of α-SMA,content of HYP and ·OH,the activity of MPO and NO were decreased（P〈0.05）,while the content of GSH and T- AOC was increased（P〈0.05）. CONCLUSION TG can improve the degree of mice pulmonary fibrosis induced by bleomycin. The mechanism may be related to the increased antioxidant capacity of organisms.