还原型谷胱甘肽对大鼠肺纤维化的干预作用

Effects of Reduced Glutathione in Rats with Pulmonary Fibrosis

目的探讨不同浓度的还原型谷胱甘肽(GSH)对大鼠肺纤维化的抗氧化干预作用并与传统激素进行比较。方法将健康的SD大鼠108只随机分为对照组、模型组、地塞米松干预组、小剂量GSH干预组、中剂量GSH干预组和大剂量GSH干预组,每组18只。除对照组外,其余组大鼠均经气管内注入博来霉素制造肺纤维化模型,根据组别予以相应的地塞米松或不同剂量GSH干预。各组分别于造模后第7、14、28 d随机抽取6只处死。通过HE染色、Masson胶原染色分析肺泡炎和肺纤维化程度,并通过比色法检测各组测肺组织匀浆GSH、羟脯氨酸、超氧化物歧化酶(SOD)及谷胱甘肽过氧化物酶(GSH-Px)浓度。结果在造模第7 d和14 d时,模型组和干预组大鼠肺泡炎程度较对照组显著增加(P<0.05),第28 d时干预组肺纤维化程度均较模型组显著减轻(P<0.05)。第7 d时模型组肺组织GSH含量显著低于对照组(P<0.05),干预组较模型组显著升高(P<0.05),地塞米松干预组和小剂量GSH干预组显著低于对照组(P<0.05),大剂量GSH干预组显著高于地塞米松干预组(P<0.05)。造模后第7、14、28 d地塞米松干预组和GSH干预组羟脯氨酸含量较模型组显著降低(P<0.05),第14 d时中、高剂量GSH干预组显著低于地塞米松干预组(P<0.05)。与对照组比较,模型组各时间点肺组织匀浆液中SOD和GSH-Px水平均显著降低(P<0.05),给予不同剂量GSH干预后,肺组织匀浆SOD及GSH-Px水平较模型组显著增加(P<0.05)。结论还原型GSH能显著降低大鼠肺纤维化程度,但与地塞米松比较其效果并无明显优势。

Objective To explore the antioxidant effects of reduced glutathione on rat pulmonary fibrosis compared with traditional corticosteroid. Methods One-hundred and eight healthy SD rats were randomly divided into 6 groups,ie. a control group,a model group,a dexamethasone group,a low-dose glutathione group,a middle-dose glutathione group,and a high-dose glutathione group,with 18 rats in each group. The pulmonary fibrosis model was established by intratrachially instillation of bleomycin in all rats except the control group. The severity of lung fibrosis was evaluated by HE staining and Masson staining of collagen,and measurement of glutathione,hydroxyproline,superoxide dismutase（ SOD）,glutathion peroxidase（ GSH-Px） in lung tissue homogenate by photocolorimetric method. Results On 7thday and 14 th day after bleomycin instillation,the severity of alveolitis in the model group,the dexamethasone group,and three glutathione intervention groups was significantly reduced compared with the control group（ P 〈 0. 05）.On 28 thday,the severity of lung fibrosis was significantly reduced in the dexamethasone group and three glutathione intervention groups compared with the model group（ P 〈 0. 05）. On 7thday,lung glutathione content was significantly lower in the model group compared with the control group（ P 〈 0. 05）,significantly higher in the dexamethasone group and three glutathione intervention groups compared with the model group（P 〈 0. 05）,significantly lower in the dexamethasone group and the low-dose glutathione group compared with the control group（ P 〈 0. 05）,and significantly higher in the high-dose glutathione group compared with the dexamethasone group（ P 〈 0. 05）. On 7th,14 th,and 28 thday,the hydroxyproline content in the dexamethasone group and three glutathione intervention groups decreased significantly compared with the model group（ P 〈 0. 05）. On 14 thday,the hydroxyproline content in the middle-dose and high-dose glutathione groups was significantly lower than that in the dexamethasone group（ P 〈 0. 05）. SOD and GSH-Px were significantly reduced in the model group compared with the control group on all time points（P 〈 0. 05）,but significantly increased after intervention by different doses of glutathione（ P 〈 0. 05）.Conclusion Reduced glutathione can significantly reduce the degree of pulmonary fibrosis in rats,but has no obvious advantage over dexamethasone.