平肺口服液对急性放射性肺损伤大鼠肺损伤及p38MAPK/Nrf2/HO-1信号通路的影响

Effect of Pingfei oral liquid on lung injury and p38MAPK/Nrf2/HO-1 signal pathway in rats with acute radiation induced lung injury

目的探讨平肺口服液对急性放射性肺损伤大鼠肺损伤的影响及其可能作用机制。方法将18只健康雄性SD大鼠随机分为正常组、模型组及平肺口服液组,每组6只。模型组及平肺口服液组大鼠给予20 Gy X射线全胸单次照射建立急性放射性肺损伤模型,自造模当日开始,平肺口服液组大鼠灌胃平肺口服液20 g/(kg·d),正常组和模型组大鼠灌胃等量生理盐水,均1次/d,连续28 d。观察并记录各组大鼠一般状况及体重;灌胃28 d结束后处死各组大鼠,摘取全肺,观察肺组织大体形态,计算肺指数,HE染色观察肺组织病理形态,对肺泡炎症进行评分,免疫组化法测定肺组织中血红素氧合酶1(HO-1)、核因子E2相关因子2(Nrf2)、p38丝裂原活化蛋白激酶(p38MAPK)蛋白表达情况。结果平肺口服液组大鼠一般状况明显好于模型组,大鼠脱毛程度较轻,照射后28 d体重明显高于模型组(P<0.05);肺组织色泽、质地、充血水肿情况较模型组轻,无胸腔积液。模型组大鼠肺指数明显高于正常组(P<0.05),平肺口服液组明显低于模型组(P<0.05)。HE染色显示模型组大鼠肺组织发生广泛炎性改变,肺泡炎评分明显高于正常组(P<0.05);平肺口服液组整体炎性改变程度较模型组轻,肺泡炎评分明显低于模型组(P<0.05)。模型组大鼠肺组织中HO-1和p38MAPK蛋白表达IOD值均明显高于正常组(P均<0.05);平肺口服液组大鼠肺组织中HO-1和Nrf2蛋白表达IOD值均明显高于模型组(P均<0.05),p38MAPK蛋白表达IOD值明显低于模型组(P<0.05)。结论平肺口服液可能通过调控p38MAPK/Nrf2/HO-1信号通路减轻急性放射性肺损伤大鼠的肺泡损伤。

Objective It is to investigate the effect of Pingfei oral liquid on lung injury in the rats with acute radiation-induced lung injury and to explore its possible mechanism.Methods Eighteen healthy male SD rats were randomly divided into normal group,model group and Pingfei oral liquid group,with 6 rats in each group.The rats in the model group and the Pingfei oral liquid group were given a single dose of 20 Gy X ray to the whole chest to establish models of acute radiation lung injury.Since the day of modeling,the rats in the Pingfei oral liquid group were given Pingfei oral liquid 20 g/(kg·d)by gavage,and the rats in the normal group and the model group were given the same amount of normal saline,all once a day,continuously treated for 28 days.The general condition and weight of the rats in each group were observed and recorded.After 28 days of intragastric administration,the rats in each group were killed,their whole lungs were harvested to observe the general morphology of lung tissue,and the lung index was calculated,the pathological morphology of lung tissue was observed with HE staining,and the alveolar inflammation was scored.The expression of heme oxygenase-1(HO-1),nuclear factor E 2 related factor 2(Nrf2),and p38 mitogen activated protein kinase(p38MAPK)proteins in lung tissue were measured with immunohistochemistry.Results The general condition of rats in the Pingfei oral liquid group was significantly better than that in the model group,the degree of hair removal was less,and the body weight 28 days after irradiation was significantly higher than that in the model group(all P<0.05);The color,texture,congestion and edema of lung tissue were lighter than those in the model group,and there was no pleural effusion.The lung index of rats in the model group was significantly higher than that in the normal group(P<0.05),and that in the Pingfei oral liquid group was significantly lower than that in the model group(P<0.05).HE staining showed that the lung tissue of the model group had extensive inflammation,and the alveolitis score was significantly higher than that of the normal group(P<0.05);The overall inflammation of Pingfei oral liquid group was lighter than that of the model group,and the score of alveolar inflammation was significantly lower than that of the model group(P<0.05).The IOD values of HO-1 and p38MAPK protein expression in the lung tissues of the model group were significantly higher than those of the normal group(P<0.05);The IOD values of HO-1 and Nrf2 protein expression in lung tissue of rats in Pingfei oral liquid group were significantly higher than those in model group(P<0.05),and the IOD values of p38MAPK protein expression were significantly lower than those in model group(P<0.05).Conclusion Pingfei oral liquid may reduce the alveolar injury in rats with acute radiation-induced lung injury by regulating p38MAPK/Nrf2/HO-1 signal pathway.