柚皮素通过调控Nrf2/HO-1信号通路对百草枯中毒大鼠急性肺损伤保护的作用

Protective effect of naringenin on paraquat-induced acute lung injury in the rats by the regulation of Nrf2/HO-1 pathway

目的探究柚皮素(NAR)对百草枯(PQ)中毒大鼠急性肺损伤(ALI)的保护作用机制。方法SPF级雄性SD大鼠随机分为对照组(Con组),PQ模型组(PQ组),NAR低剂量组(NAR-L组)和NAR高剂量组(NAR-H组),每组18只。PQ组大鼠灌胃25 mg/kg PQ溶液,NAR-L组和NAR-H组在灌胃25 mg/kg PQ溶液1 h后分别灌胃25 mg/kg和100 mg/kg NAR,Con组灌胃等量生理盐水。分别检测处理24、48、72 h时各组大鼠体质量、肺系数、肺湿干质量比(W/D),以及肺组织丙二醛(MDA)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)水平;苏木素-伊红(HE)染色观察24、48、72 h时大鼠肺组织病理学变化;荧光定量聚合酶链反应(PCR)和Western blot检测肺组织中Nrf2和HO-1 mRNA和蛋白表达水平。结果与Con组比较,各时间点PQ组大鼠体质量、肺组织SOD和GSH-Px活力显著降低(P<0.05),而肺系数、肺组织W/D比值及MDA含量显著升高(P<0.05);与PQ组比较,NAR处理后大鼠体质量、肺组织SOD和GSH-Px活力显著升高(P<0.05),而肺系数、肺组织W/D比值及MDA显著降低(P<0.05)。PQ可诱导大鼠肺组织出现显著损伤,而NAR高剂量处理可显著改善大鼠肺组织病理损伤。与PQ组比较,NAR-L组和NAR-H组大鼠肺组织中核因子E2相关因子2(Nrf2)和血红素氧化酶-1(HO-1)的mRNA和蛋白水平均显著升高(P<0.05),且NAR-H组显著高于NARL组(P<0.05)。结论NAR可以通过激活Nrf2/HO-1信号通路,促进抗氧化酶SOD和GSHPx的释放,改善PQ中毒大鼠引起ALI。

Objective To investigate protective effect and the mechanism of naringenin(NAR) on paraquat( PQ)-induced acute lung injury( ALI) in rats. Methods SPF male SD rats were randomly divided into normal group(Con group),PQ model group( PQ group),NAR low-dose group( NAR-L group) and NAR high-dose group( NAR-H group),18 rats in each group. Rats in PQ group were given 25 mg/kg paraquat solution by gavage,NAR-L group and NAR-H group were given25 mg/kg and 100 mg/kg NAR respectively after the gavage of 25 mg/kg paraquat for 1 h. The Con group was given the same amount of normal saline. The body mass,lung coefficient,wet-to-dry weight( W/D) ratio and the levels of malondialdehyde( MDA),superoxide dismutase( SOD) and glutathion peroxidase( GSH-Px) level in lung tissues of rats were detected at 24,48 and 72 h after treatment. Histopathological changes of rat lung were observed by HE staining at 24,48 and 72 h aftertreatment. Real time PCR and Western blot were used to detect mRNA and protein expression levels of Nrf2 and HO-1. Results Compared with the Con group,the body mass and the levels of SOD and GSH-Px in lung tissue of rats were decreased significantly in PQ group( P<0. 05),but the lung coefficient,W/D value and the MDA levels in lung tissue were increased significantly( P<0. 05).Compared with the PQ group,the body mass and the levels of SOD and GSH-Px in lung tissue of rats was increased significantly( P<0. 05),and the lung coefficient,W/D ratio and MDA levels in lung tissue were decreased significantly in NAR-H group( P<0. 05). PQ induced inflammatory cell infiltration,hemorrhage,and slight collapse of the alveoli and thickening of the alveolar wall in the lung tissue of rats. NAR high-dose treatment significantly improve PQ-induced serious pathological damage of the lung tissue in rats. Compared with the PQ group,the mRNA and protein levels of Nrf2 and HO-1 in the lung tissues of rats increased significantly in both NAR-L group and NAR-H group( P<0. 05),and the mRNA and protein levels in the NAR-H group was higher than those in the NAR-L group( P<0. 05). Conclusions NAR plays a protective role against PQ-induced ALI via regulating Nrf2/HO-1 signaling pathway to promote the release of SOD and GSH-Px.