扶正剔邪搜络方改善肺纤维化大鼠肺功能的机制研究

练毅刚1,张立山1,吴华阳1,闫玉琴2,王晨3,周绍忠1,关秋红1,李德莹1,苏惠萍1*

(1.北京中医药大学东直门医院，100700；2.北京市隆福医院，北京 100700；

3.怀柔区第一医院，北京 100700)

摘要：目的通过扶正剔邪搜络方治疗肺纤维化大鼠，观察不同时相大鼠肺功能与血清指标关系,探究其作用机制及适宜疗程。方法将128只SD雄性大鼠随机分为正常对照组、模型组、中药组、激素组，每组32只。使用气管内推注博莱霉素以建立肺纤维化模型，正常对照组注射相同体积的生理盐水。造模后24 h，中药组使用扶正剔邪搜络方,0.74 g/(kg·d)，激素组使用泼尼松，5 mg/(kg·d)，正常对照组和模型组使用相同体积的生理盐水。在用药后第7、14、28、45 d时,分别观察每组肺吸气阻力(Ri)、顺应性(Cl)、用力肺活量(FVC)、吸气阻力(Ri)、呼出气量为25%～75%肺活量时平均流量(FEF25%-75%)变化、第0.2秒末呼出容积(Fev0.2)。结果1)与模型组比较，中药组14 d时FVC、FEF25%-75%、Cl显著性升高(P<0.01)，28，45 d时Fev0.2、Ri、FEF25%-75%、Cl差异有统计学意义(P<0.01,P<0.05)。2)Ⅲ型胶原14、45 d中药组表达明显低于模型组。3)中药组Smad3、4蛋白表达明显低于西药组,Smad7蛋白表达明显高于西药组。结论扶正剔邪搜络方可改善肺纤维化大鼠肺功能，其作用机制为调节Smad蛋白及降低Ⅲ型胶原蛋白表达来延缓肺间质纤维化的进展。

关键词：扶正剔邪搜络方；肺纤维化；肺功能；机制研究；大鼠

DOI:10.13463/j.cnki.jlzyy.2015.04.031

中图分类号：R285.5文献标志码： A

文章编号：1003-5699(2015)04-0410-05

基金项目:北京市自然科学基金资助项目(7102096)。

作者简介:练毅刚(1972-)，男，硕士研究生，主治医师，主要从事中医药防治肺间质纤维化研究。

收稿日期:(责任编辑：赵玉芝2014-09-21)

*通信作者:苏惠萍,电话:010-84013357，电子信箱:suhuiping@126.com。

Mechanistic investigation of Fuzheng Tixie Souluo therapeutics on lung

function of pulmonary fibrosis rats

LIAN Yigang1,ZHANG Lishan1,WU Huayang1,YAN Yuqin2,WANG Chen3,ZHOU Shaozhong1,GUAN Qiuhong1,

LI Deying1,SU Huiping1*

(1.Dongzhimen Hospital,Beijing University of Chinese Medicine,Beijing 100700,China;

2.Longfu Hospital of Beijing City,Beijing 100700,China;

3.The First Hospital of Huairou District,Beijing 100700,China)

Abstract:ObjectiveThrough Fuzheng Tixie Souluo therapeutics treatment for pulmonary fibrosis rat,observe the lung function of rat relation with serum index at various time phases and explore its mechanism of action and appropriate treatment.MethodsThe 128 SD male rats are divided into normal control group,model group,Chinese medicine group and hormone group at random,each of which has 32 rats.Except physiological saline of same volume is injected into the rats in normal control group,bleomycin is injected into the tracheas of the rats in each of other groups for modeling.After being modeled for 24 hours,Fuzheng Tixie Souluo therapeutics was used in Chinese medicine group,0.74g/(kg·d) administered;hormone group use prednisone,5 mg/(kg·d);meanwhile,the physiological saline of same volume is filled into the stomachs of the rats in other two groups till the previous day of use.On the 7 th day,14 th day,28 th day and 45 th day since administration,Observed in each group respectively the inspiratory resistance (Ri),compliance of lung (Cl),forced vital capacity (FVC),inspiratory resistance (Ri),exhaled air is 25%-75% vital capacity when the average flow rate change (FEF25%-75%),the 0.2 seconds end out of the volume (Fev0.2).Results1)Compared with the model group,on the 14th day,FVC,FEF25%-75%,Cl of Chinese medicine group obvious increase (P<0.01).On the 28 th and 45th days,forced expiration volume at 0.2 nd second (Fev 0.2),average expiration flow speed between expiration 25% VC and expiration 75% VC (FEF25%-75%),Ri and Cl are remarkably improved,the differences have statistical significances (P<0.01,P<0.05).2)Compared with that of the model group,the Co III in the Chinese medicine group is obviously weakened on the 14 th and 45 th days.3)The expressions of Smad 3 and Smad 4 in Chinese medicine group were weakened,while the expression of Smad 7 had enhanced.ConclusionFuzheng Tixie Souluo therapeutics can improve lung function of pulmonary fibrosis rats.The mechanisms may be related to the influenced by the regulation of the excessive expression of Smad,also followed the decline of Co Ⅲ.

Keywords:Fuzheng Tixie Souluo therapeutics;pulmonary fibrosis;lung function;mechanistic investigation;rat

肺纤维化(pulmonary fibrosis，PF)是多种病因导致的不同肺间质疾病的共同结局，具有致命性、进行性、慢性的疾病发展特点[1]。Dempsey等[2]报道IPF患者中位生存期约3年。本研究拟动态观察扶正剔邪搜络方治疗博莱霉素致大鼠肺间质纤维化不同时相肺功能变化，通过分析不同时相Smad3、Smad4、Smad7信号蛋白及细胞外基质(Ⅰ型胶原、Ⅲ型胶原)指标的变化[3]，以期找到扶正剔邪搜络方治疗肺间质纤维化改善肺功能的作用机制。……