丹参、人参、连翘、麦冬对肺纤维化模型大鼠肺组织中BMP-4表达的影响

Effect of Danshen(Salviae Miltiorrhizae Radix Et Rhizoma),Renshen(Ginseng Radix Et Rhizoma),Lianqiao(Forsythiae Fructus) and Maidong(Ophiopogonis Radix) on Expression of BMP-4 in Lung Tissue of Model Rats of Pulmonary Fibrosis

目的:观察丹参、人参、连翘、麦冬对博来霉素诱导的肺纤维化模型大鼠肺组织中BMP-4表达的影响,探讨这四种药物抗纤维化的作用机制。方法:将168只健康Wistar雄性大鼠随机分成空白对照组、模型组、人参组、丹参组、连翘组、麦冬组、吡啡尼酮组,每组24只。除空白对照组外,其他各组大鼠均通过气管内注射博来霉素(5 mg/kg)建立肺纤维化模型,空白对照组大鼠气管内注射等量生理盐水。造模后第4天,人参组、丹参组、连翘组、麦冬组、吡非尼酮组大鼠分别给予相应药物灌胃,空白对照组、模型组每日予等量生理盐水灌胃。分别于给药后第7天、第14天、第28天随机处死每组的8只大鼠,取大鼠左肺下叶组织作切片,观察肺组织病理学变化,并以酶联免疫分析法检测各组大鼠BMP-4水平。结果:除空白对照组外,其他各组大鼠均有不同程度的肺泡炎症及肺纤维化表现,说明造模成功。与各给药组比较,模型组大鼠肺纤维化程度最明显;给药后第7天、第14天、第28天,人参组、丹参组、连翘组、麦冬组、吡啡尼酮组大鼠肺泡炎症及肺纤维化表现较模型组减轻。建模后模型组大鼠BMP-4水平降低,与空白对照组比较,差异有统计学意义(P<0.01);连翘组、麦冬组、吡非尼酮组大鼠给药后第7天、第14天、第28天的BMP-4水平均高于空白对照组,差异有统计学意义(P<0.01);丹参组、人参组大鼠给药后第14天、第28天的BMP-4水平与空白对照组比较,差异无统计学意义(P> 0.05)。结论:丹参、人参、连翘、麦冬均能降低肺纤维化大鼠的肺纤维化程度,其中连翘、麦冬可能通过提高BMP-4水平发挥抗肺纤维化作用。

Objective:To explore the anti-fibrosis mechanism of Danshen(Salviae Miltiorrhizae Radix Et Rhizoma),Renshen(Ginseng Radix Et Rhizoma),Lianqiao(Forsythiae Fructus) and Maidong(Ophiopogonis Radix) by observing their effect on expression of BMP-4 in lung tissue of pulmonary fibrosis model rats induced by bleomycin. Methods:A total of 168 healthy male Wistar rats were randomly divided into 7 groups,including blank control group,model group,Renshen group,Danshen group,Lianqiao group,Maidong group and pirfenidone group,with 24 rats in each group. Model rats of pulmonary fibrosis were induced by injecting bleomycin(5 mg/kg) into trachea in every group except the blank control group which was injected with same amount of normal saline into trachea. On the 4 th day after the models were established,the rats in Renshen group,Danshen group,Lianqiao group,Maidong group and pirfenidone group were given corresponding medicines by gavage,while the rats in the blank control group and model group were given same amount of normal saline by gavage. On the 7 th,14 th and 28 th day after medication,8 rats in each group were killed randomly. The lower lobe tissues of the killed rats’ left lung were sliced for pathological observation,and enzyme linked immunosorbent assay(ELISA) was applied to detect the expression of BMP-4 of the rats. Results:Rats in all the groups except the blank control group had alveolar inflammation and pulmonary fibrosis,which meant the models were established successfully. The rats in the model group had the most obvious pulmonary fibrosis compared with those in the medication groups. On the 7 th,14 th and 28 th day after medication,the alveolar inflammation and pulmonary fibrosis of rats in Renshen group,Danshen group,Lianqiao group,Maidong group and pirfenidone group were milder than those in the model group. After model establishment,the level of BMP-4 of rats in the model group was reduced,and compared with that in the control group,the difference was statistically significant(P<0.01). On the 7 th,14 th and 28 th day after medication,the levels of BMP-4 of rats in the Lianqiao group,Maidong group and pirfenidone group were higher than those in the blank control group and the differences were statistically significant(P<0.01). On the 14 th and 28 th day after medication,the differences of the levels of BMP-4 among the Danshen group,Renshen group and bliank control group were not statistically significant(P> 0.05). Conclusion:Danshen,Renshen,Lianqiao and Maidong all can reduce the degree of pulmonary fibrosis of the rats. The anti-fibrosis efficacy of Lianqiao and Maidong may be related with increasing the level of BMP-4.