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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 investigate the anti-oxidative effects of different concentrations of reduced glutathione (GSH) on pulmonary fibrosis in rats and compare with traditional hormones. Methods One hundred and eight healthy SD rats were randomly divided into control group, model group, dexamethasone intervention group, low dose GSH intervention group, middle dose GSH intervention group and high dose GSH intervention group, with 18 rats in each group. Except the control group, rats in the other groups were given bleomycin through intratracheal injection to make pulmonary fibrosis model, and corresponding dexamethasone or different doses of GSH were given according to the group. Groups were randomly selected on the 7th, 14th, and 28th days after the model was established. The degree of alveolitis and pulmonary fibrosis was analyzed by HE staining and Masson collagen staining. The contents of GSH, hydroxyproline, superoxide dismutase (SOD) and glutathione Oxidase (GSH-Px) concentration. Results At the 7th day and the 14th day, the degree of alveolitis in the model group and the intervention group was significantly higher than that in the control group (P <0.05). On the 28th day, the degree of pulmonary fibrosis in the intervention group was significantly lower than that in the model group P <0.05). The level of GSH in model group was significantly lower than that in control group on the 7th day (P <0.05), and the intervention group was significantly higher than that of model group (P <0.05). Dexamethasone intervention group and low dose GSH intervention group were significantly lower than the control group Group (P <0.05), high dose GSH intervention group was significantly higher than dexamethasone intervention group (P <0.05). The levels of hydroxyproline in dexamethasone intervention group and GSH intervention group on the 7th, 14th and 28th day after modeling were significantly lower than those in the model group (P <0.05), and the levels of hydroxyproline in the GSH intervention group were significantly lower than those on the 14th day The intervention group (P <0.05). Compared with the control group, the levels of SOD and GSH-Px in the lung tissue homogenate at each time point in the model group were significantly decreased (P <0.05). Compared with the model group, the levels of SOD and GSH-Px in the lung homogenate after the intervention of different doses of GSH Significantly increased (P <0.05). Conclusion Reduced GSH can significantly reduce the degree of pulmonary fibrosis in rats, but compared with dexamethasone, its effect has no obvious advantage.