秦皮苷对肺炎克雷伯菌所致重症肺炎大鼠肺组织损伤及纤维化的作用及机制研究

Effect and Mechanism of Aesculin on Lung Injury and Fibrosis in Rats with Severe Pneumonia Induced by Klebsiella Pneumoniae

目的探究秦皮苷对肺炎克雷伯菌所致重症肺炎大鼠肺组织损伤及纤维化的作用,并分析可能的机制。方法50只大鼠随机分为对照组、模型组及秦皮苷低、中、高剂量组(10只·组^(-1)),除对照组外其余各组大鼠均建立肺炎克雷伯菌所致重症肺炎模型,并于建模成功后,秦皮苷低、中、高剂量组大鼠给予10、20、40 mg·kg^(-1)秦皮苷溶液灌胃处理(连续7 d),模型组及对照组同时间给予等量生理盐水灌胃处理。采用全自动血气分析仪检测血清中动脉血二氧化碳分压(PaCO_(2))、动脉血氧饱和度(SaO_(2))、动脉氧分压(PaO_(2));苏木精-伊红(HE)染色、胶原纤维(Masson)染色观察肺组织病理学变化并对小鼠肺纤维化程度进行评分;免疫印迹法检测各组大鼠肺组织中蛋白激酶B(Akt)、缺氧诱导因子-1α(HIF-1α)蛋白水平。结果与对照组比较,模型组大鼠血液中PaCO_(2)活性、肺纤维化评分、肺组织中p-Akt/Akt、HIF-1α、CollagenⅢ蛋白水平均升高,SaO_(2)、PaO_(2)水平均降低(P<0.05);与模型组比较,秦皮苷低、中、高剂量组大鼠血液中PaCO_(2)活性、肺纤维化评分、肺组织中p-Akt/Akt、HIF-1α、CollagenⅢ蛋白水平均降低,SaO_(2)、PaO_(2)水平均升高(P<0.05)。结论秦皮苷能够改善肺炎克雷伯菌所致重症肺炎大鼠肺组织损伤及纤维化,可能是通过抑制Akt/HIF-1α通路活化抑制胶原沉积实现的。

Objective To investigate the effect of aesculin on lung injury and fibrosis in rats with severe pneumonia caused by Klebsiella pneumoniae and analyze the possible mechanism.Methods Fifty rats were randomly divided into control group,model group and aesculetin low,medium and high dose groups(10 rats·group^(-1)).Except the control group,the rats in the other groups established the model of severe pneumonia caused by Klebsiella pneumoniae.After the model was successfully established,the rats in aesculetin low,medium and high dose groups were given 10 mg·kg^(-1),20 mg·kg^(-1)and 40 mg·kg^(-1)aesculetin solution by gavage(for 7 days).The model group and the control group were given the same amount of normal saline at the same time.The arterial partial pressure of carbon dioxide(PaCO_(2)),arterial oxygen saturation(SaO_(2))and arterial partial pressure of oxygen(PaO_(2))were measured by automatic blood gas analyzer.Hematoxylin eosin(HE)staining and collagen fiber(Masson)staining were used to observe the pathological changes of lung tissue and score the degree of pulmonary fibrosis in mice.The protein levels of protein kinase B(Akt)and hypoxia inducible factor-1α(HIF-1α)were detected by Western blot.Results Compared with those of the control group,PaCO_(2)activity in blood,pulmonary fibrosis score,p-Akt/Akt,HIF-1α and Collagen Ⅲ protein levels in lung tissue of the model group increased,the levels of SaO_(2)and PaO_(2)were decreased(P<0.05).Compared with those of the model group,the PaCO_(2)activity in blood,pulmonary fibrosis score,p-Akt/Akt,HIF-1α and Collagen Ⅲ protein levels in lung tissue of rats in low,medium and high-dose aescin groups were decreased,the levels of SaO_(2)and PaO_(2)increased(P<0.05).Conclusion Aescin can improve lung injury and fibrosis in rats with severe pneumonia caused by Klebsiella pneumoniae,possibly by inhibiting Akt/HIF-1α of collagen deposition by pathway activation.