氨氯地平对肺纤维化大鼠的影响研究

目的  研究氨氯地平对大鼠肺纤维化的保护作用和可能的分子机制，为肺纤维化的治疗寻找新的途径。方法  选取240只实验大鼠进行研究，随机分为空白组、模型组、吡非尼酮组和氨氯地平组，每组各60只。模型组、吡非尼酮组和氨氯地平组采用气管内灌注博来霉素建立肺纤维化大鼠模型，空白组则气管内灌注等量生理盐水；然后空白组和模型组大鼠给予相同量生理盐水处理，氨氯地平组大鼠则给予1/2量的氨氯地平和1/2量的生理盐水处理；吡非尼酮组给予1/2量的吡非尼酮和1/2量的生理盐水处理。采用单因素方差分析和u检验分析1、2及4周后4组大鼠肺泡炎、肺纤维化的评分，并分析大鼠的血小板反应蛋白1（TSP-1）、转化生长因子β1（TGF-β1）及I型胶原和III型胶原mRNA的含量变化情况。结果  氨氯地平组和吡非尼酮组大鼠各时间段的TSP-1、TGF-β1及I型胶原和III型胶原mRNA的含量均低于模型组（P <0.05），且氨氯地平组较吡非尼酮组也降低（P <0.05），大鼠的肺泡炎和肺纤维化评分结果显示氨氯地平组和吡非尼酮组低于模型组（P <0.05），且氨氯地平组显著低于吡非尼酮组（P <0.05）。结论  氨氯地平可能通过抑制TGF-β1、TSP-1的生成水平和减少I型胶原和III型胶原mRNA的表达达到减轻大鼠肺组织肺泡炎及肺纤维化程度的临床效果。

Effect of Amlodipine on pulmonary fibrosis in rats

Objective To study the protective effect of Amlodipine on pulmonary fibrosis in rats and the possible molecular mechanism, so as to find new ways for the treatment of pulmonary fibrosis. Methods Totally 240 rats were divided into control group, model group, Pirfenidone group and Amlodipine group at random. The rats in the model group, Pirfenidone group and Amlodipine group were perfused with Bleomycin through trachea to build the model of pulmonary fibrosis, those in the control group were perfused with saline. Then the rats in the control and model groups were given normal saline, but the rats of the Amlodipine group and the Pirfenidone group were treated with half volume of Amlodipine and Pirfenidone respectively together with half amount of normal saline. Single factor analysis and U test were used to analyze the pulmonary fibrosis score and alveolitis score at 1 , 2 and 4 weeks in the 4 groups, and also the content of thrombospondin 1 (TSP-1), TGF-β1 and mRNA of type I collagen and type III collagen was analyzed. Results The four indexes in the Amlodipine group and the Pirfenidone group were significantly lower than those in the model group at each time point (P < 0.05), they were obviously lower in the Amlodipine group than in the Pirfenidone group (P < 0.05). The alveolitis and pulmonary fibrosis scores in the Amlodipine and Pirfenidone groups were significantly lower than those in the model group (P < 0.05), and they were obviously lower in the Amlodipine group than in the Pirfenidone group (P < 0.05). Conclusions Amlodipine can significantly reduce lung alveolitis and pulmonary fibrosis, possibly through inhibition of TGF-β1 and TSP-1 and reduction of type I and III collagen mRNA expression.