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DHA对脂多糖致小鼠急性肺损伤保护作用

Antioxidant mechanism of DHA on LPS-induced acute lung injury (ALI) in mice

  • 摘要: 目的观察二十二碳六烯酸(DHA)预防脂多糖(LPS)性小鼠急性肺损伤(ALI)的效果,探讨其抗氧化作用机制。方法雄性昆明种小鼠经灌胃给予DHA 250、500 mg/kg,连续10 d,然后经腹腔注射6 mg/kg脂多糖建立ALI模型;染毒16 h后,分别对各组动物肺组织进行病理学观察,支气管-肺泡灌洗液(BALF)和肺脏中氧化、抗氧化指标检测。结果脂多糖明显损伤肺组织氧化和抗氧化系统,DHA能明显改善脂多糖导致的肺脏病理学改变;给予250、500 mg/kg的DHA可分别使肺脏髓过氧化酶活性比脂多糖组降低12.2%和27.6%(P<0.05或P<0.01),丙二醛降低12.5%和25.5%(P<0.05或P<0.01);BALF和肺脏中超氧化物歧化酶活性分别升高13.2%和23.0%(P<0.05或P<0.01),19.9%和36.1%(P<0.01);谷胱甘肽过氧化物酶活性升高20.2%和33.1%(P<0.01);总抗氧化能力升高48.5%和102.4%(P<0.01)。结论 DHA对脂多糖导致的肺组织损伤具有预防作用,可能与其抗氧化功能相关。

     

    Abstract: ObjectiveTo observe the protective effects and antioxidant mechanism of docosahexaenoic acid(DHA)on lipopolysaccharide(LPS)-induced acute lung injury(ALI)in mice.MethodsMale Kunming mice were randomly divided into low dose DHA+LPS group,high dose DHA+LPS group,DHA group,LPS group,and control group.The mice of low and high dose DHA+LPS groups were treated with DHA at dosage of 250 and 500 mg/kg·bw.The mice of DHA group were treated with 500 mg/kg·bw and those in control group with equivalent corn oil by gavage daily for 10 days.At the 11th day,the mice in LPS groups were given 6 mg/kg·bw LPS by intraperitoneal injection to develop ALI model,and the mice in another two groups were treated with equivalent saline.Sixteen hours later,the lung pathologic changes together with the oxidation and antioxidant parameters in bronchial-alveolar lavage fluid(BALF)and lung tissues were detected.ResultsThe results showed that the DHA could ameliorate lung pathologic changes such as alveolar interval thickening and inflammatory neutrophilic exudates induced by LPS.LPS treatment also impaired oxidation-antioxidation balance of lung tissues.Compared to the LPS group,the medulary peroxidase(MPO)activities decreased by 12.2% (P<0.05)and 27.6% (P<0.01)and the levels of malondialdehyde(MDA)decreased by 12.5% (P<0.05)and 25.5% (P<0.01)in lung tissues following 250 mg/kg·bw and 500 mg/kg·bw treatment,respectively.The superoxide dismutase(SOD)activities were increased by 13.2% (P<0.05)and 23.0% (P<0.01)for BALF,19.9% (P<0.01)and 36.1% (P<0.01)for lung tissue.Glutathione peroxidase(GSH-PX)activities were also upregulated by 20.2% (P<0.01)and 33.1% (P<0.01),and total antioxidant capacity(T-AOC)increased by 48.5% (P<0.01)and 102.4% (P<0.01)after 250 mg/kg·bw and 500 mg/kg·b DHA administration,respectively.ConclusionDHA treatment could reduce LPS-induced lung tissue injury,and the oxidative stress amelioration might account for its preventive effects in mice.

     

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