螺内酯阻抑百草枯中毒大鼠肺纤维化的机制探讨

目的观察螺内酯能否阻抑百草枯（PQ）中毒大鼠肺纤维化及探讨其可能的作用机制。方法54只雄性SD大鼠随机分为对照组、PQ染毒组（一次性PQ80mg／kg灌胃）和螺内酯干预组（一次性PQ80mg／kg灌胃并予每天1次螺内酯100mg／kg灌胃）。各组大鼠于染毒后第7、14、28天分批处死，取肺组织行HE染色、Masson染色并做肺泡炎、肺纤维化评分，计算肺系数，测血浆及肺组织醛固酮（ALD）含量及肺羟脯氨酸含量，应用免疫组化法测肺组织转化生长因子-β1（TGF-β1）及α-平滑肌肌动蛋白（α—SMA）蛋白的表达。结果染毒组和干预组血浆、肺组织ALD含量均较对照组升高，第14天始差异有统计学意义（P〈0．05）；干预组各时间点大鼠肺泡炎和肺纤维化程度积分、肺系数、肺羟脯氨酸含量均低于染毒组（P〈0．01）；干预组第14天始肺组织TGF—β1、α-SMA蛋白的表达均低于染毒组（P〈0．05或P〈0．01）。结论ALD、TGFβ1、α—SMA可能均参与PQ中毒致肺纤维化的发病进程。螺内酯对PQ中毒大鼠肺纤维化有一定程度的阻抑作用，可能与其抑制ALD受体，并减少肺部TGF-β1和aSMA的表达有关。

Effect of spironolactone on pulmonary fibrosis caused by paraquat poisoning in rats and study of its mechanism

Objective To observe whether spironolactone would ameliorate pulmonary fibrosis caused by paraquat （PQ） poisoning in rats and explore its possible mechanism. Methods Fifty-four male SD rats were randomly divided into control group, PQ group treated intragastrically with PQ 80 mg/kg, and PQ＋ SPI group treated intragastrieally with PQ 80 mg/kg and received spironolactone 100 mg/kg once a day. The rats in each group were sacrificed and the lungs were harvested on each 7, 14 or 28 days respectively. Pulmonary coefficient in each group was calculated. Histological changes of lungs and the scores of pulmonary alveolitis and fibrosis were evaluated by HE staining and Masson Staining. Aldosterone （ALD） levels of plasma and lung tissue were detected. Hydroxyproline concentration were detected and the expressions of transforming growth factor- beta 1 （TGF-β1） and alpha-smooth muscle actin （a-SMA） in lung tissue were assessed by immunohistochemistry. Results AI- dosterone levels of plasma and lung tissue in PQ group and PQ＋SPI group were markedly higher than those in control group, and there was significant difference on 14 d and 28 d （P〈0. 05）. The scores of pulmonary alveolitis and fibrosis, pulmonary coefficient and HYP concentration in PQ＋SPI group were significantly lower than those in PQ group （P〈0.01）; The protein expression of TGF-β1 and α-SMA in lung tissue in PQ＋SPI group on 14 d and 28 d were significantly lower than those in PQ group （P〈0.05 or P〈0.01）. Conclusion ALD, TGF-β1 and a-SMA may play an important role in the development of pulmonary fibrosis caused by PQ poisoning. Spironolactone can alleviate paraquat-induced pulmonary fibrosis, which may be due to inhibition of aldosterone receptor and, in part, be associated with reduction in TGF-β1 and α-SMA.