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目的探讨异莲心碱对百草枯(PQ)诱导的小鼠急性肺损伤及肺纤维化是否有保护作用。方法一次性给不同剂量PQ分别制备小鼠急性肺损伤模型(45mg·kg-1,ip)和肺纤维化模型(100mg·kg-1,ig)。异莲心碱在给PQ前1 d开始给予至实验结束。实验分空白对照组、模型组(PQ)、单用异莲心碱组及异莲心碱治疗组(异莲心碱+PQ)。急性肺损伤模型组给予PQ后第8,24及48 h观察异莲心碱(20 mg.kg-1,ig,每天3次)对血浆及支气管肺泡灌洗液(BALF)中超氧化物歧化酶(SOD)活性、丙二醛(MDA)含量及碱性磷酸酶(ALP)活性的影响。肺纤维化组给予PQ后14 d观察异莲心碱(10,20, 40 mg·kg-1,ig,每天2次)对肺组织羟脯氨酸含量、肺组织中转化生长因子β1(TGF-β1)及基质金属蛋白酶2(MMP-2)表达的影响。同时采用HE染色方法观察两模型在上述各时间点的肺组织病理变化。结果在急性肺损伤模型中,与空白组比较,模型组的肺组织出现充血、出血、炎性渗出及水肿等病变,血浆和BALF中的SOD活性明显下降,MDA水平明显升高,而血浆中的ALP活性显著升高;与模型组比较,异莲心碱治疗组的肺组织炎症反应减轻,血浆和BALF中SOD活性明显升高,血浆中ALP活性以及血浆和BALF中MDA含量明显降低;单用异莲心碱以上指标无明显作用。在肺纤维化模型中,一次性给PQ14 d后,与空白组比较,模型组肺组织出现肺间质增厚和胶原纤维增生等病理变化,肺组织中羟脯氨酸含量明显升高(2.44±0.33 )vs(1.26±0.10 )mg·g-1湿组织;与模型组比较,异莲心碱10, 20和40mg·kg-1治疗组间质炎症及肺纤维化病变有所改善,肺组织中羟脯氨酸含量显著减少分别为(2.11±0.21), (1.94±0.24)和(1.89±0.26)mg·g-1湿组织;与模型组比较,异莲心碱40mg·kg-1治疗组肺组织中TGF-β1和MMP-2的表达明显降低。结论异莲心碱对PQ诱导的急性肺损伤及肺纤维化具有一定的保护作用。
OBJECTIVE: To investigate whether isorphine has a protective effect on paraquat-induced acute lung injury and pulmonary fibrosis in mice. Methods The acute lung injury model (45 mg·kg-1, ip) and lung fibrosis model (100 mg·kg-1, ig) were prepared by different doses of PQ. Isolimetin was given to the end of the experiment 1 d before PQ. The experiment was divided into blank control group, model group (PQ), isoniazine group alone, and isoniapine group treatment group (isolianoxine + PQ). Acute lung injury model group was treated with PQ at 8, 24 and 48 h to observe the effect of isoliensinine (20 mg.kg-1, ig, 3 times daily) on plasma and bronchoalveolar lavage fluid (BALF) in superoxide dismutase (BALF). SOD activity, malondialdehyde (MDA) content, and alkaline phosphatase (ALP) activity. The hydroxyproline content in lung tissue and transforming growth factor β1 in lung tissue were observed in lung fibrosis group at 14 days after PQ (10, 20, 40 mg·kg-1, ig, twice daily). Effects of β1) and matrix metalloproteinase 2 (MMP-2) expression. At the same time, HE staining was used to observe the pathological changes of the lung tissues of the two models at the above time points. Results In the acute lung injury model, compared with the blank group, the lung tissue of the model group developed congestion, hemorrhage, inflammatory exudation, and edema, and the SOD activity in the plasma and BALF decreased significantly, and the MDA level increased significantly. The ALP activity in the rats was significantly higher. Compared with the model group, the inflammatory reaction in the lung tissue of the isomazine group was alleviated, the SOD activity in plasma and BALF was significantly increased, and the ALP activity in the plasma and the MDA content in the plasma and BALF were significantly decreased; There is no significant effect on the above indicators of isoxin. In the pulmonary fibrosis model, after one-time administration of PQ for 14 days, compared with the blank group, lung tissue in the model group showed pathological changes such as pulmonary interstitial thickening and collagen fibrosis, and the hydroxyproline content in the lung tissue was significantly increased (2.44). ±0.33 ) vs (1.26±0.10) mg·g-1 wet tissue; compared with the model group, interstitial inflammation and pulmonary fibrosis lesions were improved in the 10, 20, and 40 mg·kg-1 isomonephrine groups. Hydroxyproline content was significantly decreased in (2.11±0.21), (1.94±0.24), and (1.89±0.26) mg·g-1 wet tissues, respectively; compared with the model group, islaninine 40 mg·kg-1 treatment group. The expression of TGF-β1 and MMP-2 in lung tissue was significantly reduced. Conclusion Isophylline has a certain protective effect on PQ-induced acute lung injury and pulmonary fibrosis.