白及颗粒对慢性阻塞性肺疾病模型大鼠肺组织α-1 antitrypsin、Neutrophil Elastase及MPO表达的影响

Effect of Baiji Granule on expression of α-1 antitrypsin,Neutrophil Elastase and MPO in lung tissue of rats with chronic obstructive pulmonary disease

关键词:  白及颗粒  慢性阻塞性肺疾病  α-抗胰蛋白酶  中性粒细胞弹性蛋白酶  髓过氧化物酶

Key words:  Baiji Granule  chronic obstructive pulmonary disease  α-1 antitrypsin  Neutrophil Elastase  MPO

摘要:

[目的] 研究白及颗粒对大鼠慢性阻塞性肺疾病（COPD）横型的治疗作用及作用机制。[方法] 60只SPF级SD大鼠分为空白对照组、模型对照组、羧甲司坦片组（0.14 g/kg）、白及颗粒高剂量组（5.4 g生药/kg）、白及颗粒中剂量组（3.6 g生药/kg）、白及颗粒低剂量组（1.8 g生药/kg）。除空白对照组外其余大鼠于实验第1、15天经气管注入0.2 mL脂多糖（LPS）溶液。第15天除外第2~28天每天给予烟熏。记录0.3 s内最大呼气容积与肺活量比值（FEV 0.3/FVC%），采用苏木精-伊红（HE）染色及免疫组化染色观察各组大鼠肺组织的病理改变。[结果] 与空白对照组比较，模型对照组FEV 0.3/FVC%显著降低（P<0.01），与模型对照组比较，白及颗粒低剂量组、中剂量组、高剂量组FEV 0.3/FVC%显著增加（P<0.01）；病理检测结果显示：与空白对照组比较，模型对照组HE染色病理分级显著增加（P<0.01），与模型对照组比较，白及颗粒中剂量组、高剂量组HE染色炎症分级显著降低（P<0.01）；与空白对照组比较，模型对照组肺脏细胞α-抗胰蛋白酶（α-1 antitrypsin）表达显著增加（P<0.05）；与模型对照组比较，白及颗粒剂低剂量组、中剂量组和高剂量组大鼠肺脏细胞α-1 antitrypsin表达显著增加（P<0.05）；与空白对照组比较，模型对照组肺脏细胞中性粒细胞弹性蛋白酶（NE）表达显著增加（P<0.05），与模型对照组比较，白及颗粒中剂量组、高剂量组大鼠肺脏细胞NE表达显著降低（P<0.05）；与空白对照组比较，模型对照组肺脏细胞髓过氧化物酶（MPO）表达显著增加（P<0.05），与模型对照组比较，白及颗粒低剂量组、中剂量组和高剂量组大鼠肺脏细胞MPO表达显著降低（P<0.05）。蛋白印迹检测结果显示：与空白对照组比较，模型对照组肺组织NE及MPO表达显著增加（P<0.05）；与模型对照组比较，白及颗粒中剂量组、高剂量组大鼠肺组织内NE及MPO表达显著降低（P<0.05）。[结论] 白及颗粒可能通过增加慢阻肺模型大鼠肺脏α-1 antitrypsin表达，降低NE及MPO的表达，起到减轻慢阻肺模型大鼠肺组织细胞炎症反应，最终产生改善COPD模型大鼠肺功能的药理作用。

Abstract:

[Objective] To study the therapeutic effect and mechanism of Baiji Granules on chronic obstructive pulmonary disease in rats. [Methods] Sixty SPF SD rats were divided into blank control group,model group,carboxymethine tablet group (0.14 g/kg),Baiji Granules high-dose group (5.4 g crude drug/kg),Baiji Granules medium-dose group (3.6 g crude drug/kg),Baiji Granules low-dose group (1.8 g crude drug/kg). Except the blank group,the rats were injected with 0.2 mL LPS solution through the trachea on the 1st and 15th day of the experiment. Smoke is given except for the 2nd day and the 15th day. The percentage of maximum expiratory volume (FEV 0.3/FVC%) was recorded. The pathological changes of lung tissue were observed by HE staining and immunohistochemical staining. [Results] Compared with the blank control group,the FEV 0.3/FVC% of the model control group was significantly reduced (P<0.01). Compared with the model control group,the FEV 0.3/FVC% of the Baiji Granules low-dose group,Baiji Granules medium-dose group,and Baiji Granules high-dose group FEV0 were significantly increased by 3% (P<0.01) and pathological results showed that compared with the blank control group,the pathological grade of HE staining in the model control group increased significantly (P<0.01). Compared with the model control group,the pathological grade of HE staining in the Baiji Granules medium-dose group,and Baiji Granules high-dose group was significantly decreased (P<0.05). Compared with the blank control group,the expression of α-1 antitrypsin in the lung cells of the model control group was significantly increased (P<0.05). Compared with the model control group,the expression of α-1 antitrypsin in lung cells of the Baiji Granules low-dose group,the Baiji Granules medium-dose group,and the Baiji Granules high-dose was significantly increased (P<0.05). Compared with the blank control group,the expression of neutrophil elastase in the lung cells of the model control group was significantly increased (P<0.05). Compared with the model control group,the expression of neutrophil elastase in the lung cells of the Baiji Granules medium-dose group and the Baiji Granules high-dose group was significantly reduced (P<0.05). Compared with the blank control group,MPO expression in lung cells of the model control group was significantly increased (P<0.05). Compared with the model control group,the expression of MPO in lung cells of rats in the low-dose,medium-dose and high-dose groups of Baiji Granules was significantly reduced (P<0.05). Western blot results showed that compared with the blank control group,the expression of neutrophil elastase and MPO in the lung tissue of the model control group was significantly increased (P<0.05). Compared with the model control group,the expression of neutrophil elastase and MPO in the lung tissue of rats in the medium and high dose groups of Baiji Granules was significantly reduced (P<0.05). [Conclusion] Baiji Granules may reduce the expression of α-1 antitrypsin in the lung of rats with chronic obstructive pulmonary disease,reduce the expression of neutrophil elastase and MPO,and reduce the inflammatory response of lung tissue in rats with chronic obstructive pulmonary disease. The lung function was improved in rats with chronic obstructive pulmonary disease.