柚皮素对急性肺损伤小鼠保护作用的机制研究

Mechanism of the protective effect of naringenin on mice with acute lung injury

目的探讨柚皮素(Nar)对急性肺损伤(ALI)小鼠的影响及其作用机制。方法15只雌性BALB/c小鼠随机分成对照组(Control组)、模型组(LPS组)、柚皮素组(LPS+Nar组)。采用气管内滴入脂多糖(5mg/kg)建立急性肺损伤小鼠模型,造模成功后24 h取动脉血和双肺组织。HE染色观察肺组织病理改变,测定肺组织湿干重(W/D)比值,检测动脉血氧分压(PaO_(2))并计算氧合指数(OI),ELISA法检测肺组织TNF-α、IL-1β浓度水平,Western blot法检测肺组织p-SGK1、α-ENaC、Na^(+)-K^(+)-ATPaseα1蛋白表达水平。结果LPS组肺泡结构大量破坏、间隔增宽、大量炎症细胞浸润、肺泡腔内可见红细胞渗出,柚皮素干预能减轻脂多糖诱导的ALI小鼠肺组织病理改变。与Control组比较,LPS组W/D、TNF-α、IL-1β水平升高(P<0.05),OI、p-SGK1、α-ENaC、Na^(+)-K^(+)-ATPaseα1蛋白表达降低(P<0.05);与LPS组比较,LPS+Nar组W/D、TNF-α、IL-1β水平降低(P<0.05),OI、p-SGK1、α-ENaC、Na^(+)-K^(+)-ATPaseα1蛋白表达升高(P<0.05)。结论柚皮素通过抑制炎症介质的释放及上调α-ENaC、Na^(+)-K^(+)-ATPaseα1蛋白表达,对脂多糖诱导的ALI小鼠具有保护作用,其机制可能与激活SGK1信号通路有关。

Objective To investigate the protective effect of naringin(Nar)on acute lung injury(ALI)mice and its potential mechanism.Methods Fifteen female BALB/c mice were randomly divided into the control group(Control group),model group(LPS group),and naringenin group(LPS+Nar group).The mice model of ALI was established by intratracheal dripping of LPS(5mg/kg).All mice were sacrificed 24 hours after successful modeling,and lung tissue and arterial blood were collected.HE staining was used to observe the pathological changes of lung tissue.The wet-dry weight(W/D)ratio of lung tissue was measured.The partial pressure of oxygen(PaO_(2))was measured,and the oxygenation index(OI)was calculated.The concentrations of TNF-αand IL-1βin lung tissue were measured by ELISA.The protein levels of p-SGK1,α-ENAC,and Na^(+)-K^(+)-ATPaseα1 in lung tissue were determined by Western blot.Results In the LPS group,the alveolar structure was greatly destroyed,with widened interstitial,a large number of inflammatory cells infiltration,and erythrocyte exudation in the alveolar cavity.The intervention of Nar could alleviate the pathological changes in the lung tissue of ALI mice induced by LPS.Compared with the Control group,the levels of W/D,TNF-α,and IL-1βwere increased in the LPS group(P<0.05),while OI and the expression of p-SGK1,α-ENAC,Na^(+)-K^(+)-ATPaseα1 were decreased(P<0.05).Compared with the LPS group,the levels of W/D,TNF-α,and IL-1βwere decreased in the LPS+Nar group(P<0.05),while OI and the expression of p-SGK1,α-ENAC,Na^(+)-K^(+)-ATPaseα1 were increased(P<0.05).Conclusion Nar has a protective effect on lipopolysaccharide-induced ALI mice by inhibiting the release of inflammatory mediators and up-regulating the expression ofα-ENaC and Na^(+)-K^(+)-ATPaseα1 proteins,and the mechanism may be related to the activation of the SGK1 signaling pathway.