理肺化纤方对肺纤维化大鼠的防治作用及对TGF-β_1/Smad3信号转导通路的影响

Preventive Effect of Lifei Huaxian Fang on Pulmonary Fibrosis in Rats and its Influence on Signal Transduction of TGF-β_1/Smad3

目的:以经方升降散为基础,加味组成理肺化纤方,研究理肺化纤方对肺纤维化的防治作用以及对信号转导分子Smad3(sekclsky mothers against dpp3,Smad3)介导的转化生长因子β1(transforming growth factor-β1,TGF-β1)信号转导通路的影响,并初步阐释其作用机制。方法:Wistar大鼠100只,体重(200±20)g,雌雄各半,随机分为5组,每组20只。模型组与各治疗组实验大鼠气管内注入博莱霉素A5复制肺纤维化模型。正常对照组和模型组给等容积生理盐水ig,理肺化纤方治疗组给药剂量为4.41 g·kg-1,强的松对照组给药剂量为1.05 mg·kg-1,强的松合理肺化纤方治疗组给等量的强的松和理肺化纤方水煎液ig,实验7,28 d末次给药后2 h,采用SABC法检测大鼠肺组织TGF-β1,Smad3的表达。观察大鼠一般情况及体重与肺系数的变化,用肺组织病理学方法观察苏木精-伊红及Masson染色切片的肺泡炎及纤维化程度,采用SABC法检测大鼠肺组织TGF-β1,Smad3,其表达采用BI-2000医学图像分析系统分析。结果:检测结果提示造模成功,各治疗组的肺系数较模型组明显减少,肺泡炎及纤维化程度较模型组明显减轻,TGF-β1,Smad3的表达减少,各治疗组与模型组相比均有疗效,以中药治疗组和中西药合并组疗效更为明显。结论:理肺化纤方对博莱霉素A5复制的大鼠肺纤维化有一定的治疗作用,其作用机制可能与减少TGF-β1,Smad3的过度表达有关。

Objective：To study preventive effect of Lifei Huaxian Fang,a prescription based on Shengjiang San,on pulmonary fibrosis.And to investigate its effect on signal transduction molecules,transformation of transforming growth factor β1（factor-β1,have TGF-β1） mediated by Sekclsky mothers against mediated dpp3（Smad3）,and to clarify the preliminary mechanism responsible for action.Method：One hundred Wistar rats weighing（200±20） g（half male and half female） were divided into 5 groups（n=20 each） randomly.The rats in model group and the treatment group were injected by bleomycin A5 within the trachea to establish pulmonary fibrosis model.Lifei Huaxian Fang administration dosage in the treatment group was 4.41 g·kg-1·d-1.Prednisone administration dosage in the prednisone control group was 1.05 mg·kg-1·d-1.The rats in the prednisone combined with Lifei Huaxian Fang group were ig treated by the above dosages jointly.For normal control group and model group were ig given the same volume of normal saline.By the 7th day and the first 28th day SABC method was applied to detect lung tissue TGF-β1,Smad3 expression in the rats with the help of BI-2000 medical image analysis system.The general situation,body weight and changes in pulmonary coefficient were observed for the rats.Alveolar inflammation and fibrosis degree in lung were evaluated by pathological slides with staining of hematoxylin-Masson.Result：The results suggest the success of mould establishment.The lung inflammation,fibrosis and lungs coefficient were significantly reduced in the treatment group compared with that in the model group.In each of the treated groups,the alveolar degree was lightening obviously,TGF-β1,Smad3 expression were reduced,compared with those in the model group.The effects in the group of combined prednisone with Lifei Huaxian Fang were more obvious.Conclusion：Lifei Huaxian Fang has certain treatment effect for pulmonary fibrosis in the model rats induced by bleomycin A5.The mechanisms may be related to inhibition of the excessive expression of TGF-β1,Smad3.