Treatment Of Pulmonary Fibrosis Compound Prescription Optimization Principle And Compatibility

The main clinical manifestations of Idiopathic pulmonary fibrosis(I PF)is progression of breathing difficulty. With the development of the disease,accompanied by stimulating a dry cough and asthma. The t hesisutilize System finishing excavation technology to summarize Zh ongjing’s treating cough and asthma syndrome medication regularly, T his issuecombining with the experience of herbs used in treatment o f IPF in recent years and the experimental research of drugs useing on the treatment of IPF as well,then track out the efficient optim ization compounds to treat IPF.Using the mixture of uniform design some compounds(Dose the ratio of different but the same drugs). Choo se efficacy of indicators from the mortality of pulmonary fibrosis model of male ICR mice induced by bleomycin. Then use7d,28d mortalit y and Hyp content efficacy index to search the optimal compatibilit y mode of the compound.Provide experimental basis for clinical trea tment of IPF rational drug use of traditional Chinese medicine.The theoretical researchTheoretical research one:Zhongjing,s experience on cough and asthm a syndrome patterns of syndrome differentiationResearching and analysising arrangements about "cough","breath" and "short breathe" in the theory of shanghan and jinguiyaolue compreh ensively and systemly,exploring Zhongjing’s experience in the diffe rentiation and treatment of cough and gasp,revealing Zhongjing medi cine in treatment of cough and gasp. Based on dialectical treatment, on the basis of medicine certificate accordingly,point out Zhongjin g thret cough commonly used Ganjiang,Xixin and Wuweizi.Zhongjing ex perienced in using Mahuang to treat asthma for its effectively in r eleasing lungs and asthma.Mahuang often interacting with Banxia,alt ogether plays inverse and asthma effect.Theoretical research two:The basis to select compound to treat IPF Based on the traditional Chinese medicine for idiopathic pulmonary fibrosis and the understanding of the course of the general law of development,start with symptomatology,Thought the disease early can belong to the traditional Chinese medicine "cough" and "take card" category,think that the basic pathological changes of lung qi and Yin deficiency. With the development of the disease,cyanosis,dark pu rple tongue,lips,symptoms like "blood stasis syndrome in TCM comes along,as well as hand,foot and inverse cold, skin and hair is cool "Yang deficiency syndrome;The further development,Will add to cough and gasp the intensified what such as "lung kidney two virtual",an d fatigue, anorexia, angular "virtual fatigue syndrome." From the r ule of zhongjing’s syndrome differentiation to cough and gasp,and t he literature reported in the clinical treatment of IPF main syndro mes of traditional Chinese medicine for this topic for the treatmen t of IPF Chinese herbal compound of basic formula,ultimately determ ines the use for IPF compound optimization selection of specific dr ugs are:Mai dong,Fa banxia,Gan jiang,Wu weizi,Zhi mahuang,Zhi huang qi,Dang shen,Zhi gancao,Dang gui,Dan shen,Huang qin,Jie geng.The experiment researchExperiment one:Used to treat IPF compound different compatibility p roportion of pharmacodynamics researchMethod:195male ICR mice were randomly divided into13groups,thenormal gr oup,the model group and11Chinese medicine compound group. After an esthesia all the mice were tracheotomy,then inject bleomycin into t he trachea,made Idiopathic pulmonary fibrosis model. After the model is successful,11compound groups of rats were given mixing uniform design good equals the total dose and ratio of different11first compound every day. Normal control group and the pathologic model gr oup rats were given the saline lavage at the same time. Observe the survival state and the dead index of the groups rats.Observe the su rvival state of the groups of mice,the weight change,Statistical de aths. The determination of Hyp content in lung tissue use alkaline h ydrolysis;HE staining and Masson staining;to observe the mice lung pathological changes.The experimental results and discussion:1The general situation of rats:compared with model rats,The7d,Comp ound1,5groups of weight gain in mice, Compound11mice weight declin e;The14d,the compound group1weight gain in mice;The28d,the comp und group1weight gain in mice.2The effect of each compound on mice mortality and compatibility o timization:(1)The effects of compound on mice mortality:2,5groups of compound for improving the survival rates of early pulmonary fi rosis(inflammatory stage)in mice.The1,2,5,6groups of compound fo improving survival rates for pulmonary fibrosis model mice throug out the cycle.(2)Groups of mice survival28d and28d average weigh has a linear correlation,Showed the higher weight,pulmonary fibro is mice survival advantage,the more obvious.(3)7d mortality for ef icacy index to optimization:Maidong,Danggui,Wuweizi,Jiegeng,Huangq n plays a leading role on mortality reduction,Ganjiang,Zhihuangqi ower the auxiliary role on mortality.(4)28d mortality for efficacy index to optimization:Maidong,Zhihuangqi,Danggui,Jiegeng play a le ding role.3Each compound28dhyp content in lung tissue in mice and the infl ence of compatibility optimization:(1)The compound28dhyp content in lung tissue of model mice:Group1compound can obviously reduce the lung tissue of mice Hyp content,compound11group was obviousl higher Hyp content in lung tissue of mice;(2)The type of28d has linear correlation between the mortality and28d hyp content show that effectively restrain the collagen deposition in pulmonary fib osis organization has positive significance to the improvement of urvival rates.(3)28d Hyp content in lung tissue in mice as compati ility optimization effectiveness index:Wuweizi,Jiegeng,Zhihuangqi, higancao,Huangqin play a leading role,Maidong,Danshen play a suppl mentary role.4Lung tissue morphology observation:(1)HE dyeing observation of in lammatory cells infiltration:thel,2,5compounds Suppresses the pulm nary fibrosis of lung tissue inflammation markedly,it also promote the repair of lung parenchyma cells and can reduce the collagen de osition.(2)Masson staining to observe the degree of fibrosis:compo nd1,2,5,6groups of collagen content in model group decreased sig ificantly,showed that the compound in reducing the collagen deposi ion and fibrosis of the role of resistance significantly. In Hyp content of the optimization of drug efficacy index basic con tains7d and28d mortality for optimization of drug efficacy index. Due to the difference of efficacy index shows that the optimization results and differences,but no matter which index optimization,the results are the main drugs are Wuweizi,Jiegeng,Zhihuangqi,Zhiganca o,Huangqin,Maidong,Danggui,but their compatibility proportion is di fferent.The result show that these drugs of compatibility of compou nd for the treatment of pulmonary fibrosis have certain effect.Experiment two:Study of pharmacodynamics and validation testMethod:60male ICR mice were randomly divided into6groups,the normal rat s,the model rats,the compound5groups,7d optimization group of mor tality,28d optimization group of mortality,sequential treatment gro up.Testing each Hyp content in lung tissue of mice and CTGF,IL-6,Fo xp3mRNA content.The experimental results and discussion:1Compared with model group,Sequential treatment group to reduce the collagen deposition in the lung tissue,Or cut some cytokines(CTGF, IL-6)gene expression level has remarkable curative effect, this for the staging treatment of IPF(early in lung nourishing both qingrej iedu,late notice to nourish Yin Yang,qi and nourishing blood)provid es the experimental basis.2Compared with model group,Sequential therapy group and28d mortali ty optimization compound can rise Foxp3mRNA expression level, the28d optimization group compound can reduce mortality CTGFmRNA and IL-6mRNA expression level,Sequential treatment group compound can reduc e CTGFmRNA expression level.Results show that the excessive CTGF an d IL-6gene expression, and lack of Foxp3gene expression might be IPF important factors of the disease.