异莲心碱对百草枯诱导的小鼠急性肺损伤及肺纤维化的保护作用

摘要

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(45 mg·kg-1, ip)和肺纤维化模型(100 mg·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PQ 14 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40 mg·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40 mg·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.%AIM To evaluate the beneficial effects of isoliensinine on paraquat(PQ)-induced acute lung injury and pulmonary fibrosis and explore the mechanism of its action. METHODS PQ (45 mg·kg-1, ip)-induced acute lung injury and PQ (100 mg·kg-1, ig)-induced pulmonary fibrosis were prepared. At 8, 24 and 48 h after PQ administration, the effects of isoliensinine (20 mg·kg-1, ig, 3 times a day, from 24 h before PQ administration to the end of experiment) on activity of superoxide dismutase (SOD), alkaline phosphatase (ALP) and the content of malondialdehyde (MDA) in plasma and bronchoalveolar lavage fluid (BALF) of acute lung injury groups were evaluated respectively. On the 14 d following PQ ingestion, the effects of isoliensinine (10, 20 and 40 mg·kg-1, ig, twice a day, from 24 h before PQ administration to the end of experiment) on hydroxyproline content, transforming growth factor β1 (TGF-β1) and matrix metalloproteinase-2 (MMP-2) expressions and the histopathological changes in lung tissues of pulmonary fibrosis groups were observed. RESULTS In the acute lung injury model, isoliensinine (20 mg·kg-1) significantly increased SOD activity, and decreased MDA content and ALP activity, as well as ameliorated the histopathological damage of lung tissue compared with PQ group. However, the indexes mentioned above in isoliensinine alone group did not change obviously compared with normal saline group. In the pulmonary fibrosis model, isoliensinine (10, 20 and 40 mg·kg-1) resulted in a dose-dependent decrease of hydroxyproline content compared with PQ group [(2.11±0.21), (1.94±0.24) and (1.89±0.26), respectively, vs (2.44±0.33) mg·g-1 wet tissue]. The expressions of TGF-β1 and MMP-2 in the lung tissue of the isoliensinine 40 mg·kg-1+PQ group were significantly less than those of the PQ group. Furthermore, isoliensinine could improve the histopathological changes of fibrosis as comparison with PQ group. CONCLUSION Isoliensinine has protective effects on PQ-induced acute lung injury and pulmonary fibrosis.