| ObjectiveIdiopathic pulmonary fibrosis(IPF)is an interstitial lung disease with unknown cause and characterized by diffuse alveolitis and alveolar structural disorder.The main clinical manifestations of IPF are progressive dyspnea,restrictive ventilatory dysfunction and gas exchange disorders.Currently,clinical medicine is lack of effective methods to treat this disease.In recent years the study of traditional Chinese medicine in the treatment of IPF is gradually thorough.In this study,retrospective analysis was conducted in the cases of IPF patients to explore the clinical datas,at the same time I summarized my tutor's theoretical thinking in the treatment of IPF,and the clinical experience of treating this disease with the method of Bushenyifeixiaozheng.It was found that the expression of SP-C and the abnormal distribution of it were the key to the induction of endoplasmic reticulum stress(ERS)of IPF.This study was designed to examine the effects of BushenYifeiXiaozheng Decoction on the expression of SP-C in the lung tissues and the ultrastructure of pulmonary fibrosis in rats,and on the expression and distribution of SP-C in the process of epithelial to mesenchymal cell transition(EMT)induced by TGF-?1.The aim was to explore the interventing mechanism of Bushenyifeixiaozheng decotion in ERS and provide a new basis for the clinical application of its treatment of pulmonary fibrosis.Methods1.This study adopted the method of retrospective study.We Collected a total of 28 patients with the diagnosis of IPF treated in respiratory ward of Dongzhimen Hospital in January 2010-August 2016.According to the preliminary designed observation table "clinical data of idiopathic pulmonary fibrosis",we collected related contents,including general demographic data,clinical symptoms,signs and objective clinical indicators,TCM syndrome information.Through statistical analysising,we explore the clinical and symptomatic characteristics of IPF patients.In this paper,my tutors experience on the treatment of IPF was summarized,and the origin of the theory "Lung collaterals miniature remove lump" was explored.2.In vivo,IPF rat models were caused by Bleomycin,then they were treated with BushenYifeiXiaozheng Decoction,Animals were randomly divided into normal group,model group,positive control group(pirfenidone),traditional Chinese medicine preventing group,traditional Chinese medicine treating group,traditional Chinese medicine preventing and treating group.The ultrastructural changes of lung tissue in different groups were observed under electron microscope.The expression of SP-C in alveolar surfactant was observed by immunohistochemistry.3.In vitro experiments,the cell models were caused by TGF-?1(5 ng/ml),which stimulating EMT in A549 cell.Grouping are the normal group,the TGF-?1 group,TGF-?1 inhibitor group(2?mol/L),freeze-dried powder 1 group(100?g/ml),freeze-dried powder 2 group(200?g/ml).By drug intervention,immunofluorescence technique was used to observe the change in the form of A549 cells and the different expression of a-SMA,one of the markers of EMT in the cell,laser confocal microscope was used to detect the expression of SP-C in the cell.Results1.The analysis of relevant data of IPFThere were 28 cases met with the inclusion criteria.Of which 16 cases were male gender(57.1%),12 cases were female gender(42.9%).Patients with the course of the disease at 1-5 years were 20 cases(71.4%),6 cases were with the course of 6-10 years,15cases(53.6%)were treated for 8-14 days,5 cases(17.9%)were for 1-7 days.Among the drugs patients received before being admission into hospital,anti-infective drugs as well as drugs having the effect of relieving cough and reducing sputum accounted for 13cases(46.4%).Among the combined spectrum of disease,Lung infection ranked first(18cases,64.3%),followed by coronary heart disease(12cases,42.9%),COPD/chronic bronchitis(7cases,25%),Gastroesophageal reflux(7 cases,25%).The proportion of male smokers with IPF was significantly higher than that of females,12cases for man(85.2%),2cases for women(14.3%).2 cases were with IPF family genetic history.Among the common clinical symptoms,cough was in the leading position(28cases,100%),followed by sputum(27cases,96.4%),according to the proportion,other symptoms were chest tightness of breath(24cases,85.7%),wheezing(23cases,82.1%),shortness of breath(15cases,53.6%)and exertional dyspnea(14cases,50.0%).HRCT of patients with IPF showed that,IPF terminal phase of the typical CT"honeycomb lung" accounted for the largest proportion(14cases,50%),followed by grid shadow(12cases,42.9%),ground glass shadow was least(2cases,7.1%).The coagulation function of most IPF patients were abnormal.There were 12 cases with increased D-dimer(48%),7 cases with increased fibrinogen(28%),which indicated the body was in the state of hypercoagulable.IPF patients were associated with elevated tumor markers,as abnormally elevated serum CEA(75%),cytokeratin 19 fragment(75%),CA199(50.0%),CA125(37.5%),specificity enolization enzyme(37.5%),CA153(31.3%),ferritin(18.8%).In the syndrome distribution documents of IPF patients,the ratio of qi deficiency syndrome was 82.1%,followed by blood stagnant(67.9%),phlegm heat syndrome(53.6%),Yin deficiency syndrome(53.6%).In the two combinations,the ratio of Qi deficiency and blood stagnant was(16.3%),followed by qi and yin deficiency(14.1%).In the three combinations,according to the proportion,Qi andYin deficiency and blood stagnant and qi deficiency blood stasis phlegm turbidity took up the highest proportion(20.5%).2.Animal experiment showed:Bushenyifeixiaozheng decoction could reduce the expansion,distortions of ER in IPF rat and reduced the abnormal stack of SP-C.3.In vitro experiments,Bushenyifeixiaozheng decoction could reduce the expression of a-SMA in cells.Immunofluorescence result showed that the expression of a-SMA in TGF-?1 inhibitor group was lower than that in TGF-?1 group,P<0.01,which was with significant difference.The expression of a-SMA was decreased in each treatment group,and the effect of 100?g/ml freeze-dried powder was the best.The results of SP-C expression on the cell surface showed that Bushenyifeixiaozheng decoction powde 2 group decreased,compared with model group and TGF-?1 inhibitors group,P>0.05,the results showed no statistical difference.Flow cytometry instrument was used to detect cell apoptosis rate,TGF-?1 group of apoptosis rate was higher than normal group,P<0.01,with statistically difference,The apoptotic rate of TGF-?1 inhibitor group and freeze-dried powder group were lower than that of model group.Conclusion1.With reference to "expert consensus about the diagnosis and treatment of idiopathic pulmonary fibrosis in China",The clinical features of IPF patients in this study were consistent with the epidemiological observations,tumor markers and coagulation abnormalities were associated with IPF.TCM syndrome elements were given priority to"deficiency,blood stasis and phlegm".Tutor thought" pulmonary microfractal Zhengjia"could be used to explain the pathological mechanism of IPF,and this study could provide new data to support this theory.2.By interventing ERS,regulating the expression of SP-C on the cell surface,Bushenyifeixiaozheng Decoction could reduce the alveolar epithelial cell apoptosis,interfer the process of EMT,delay the pathological process of idiopathic pulmonary fibrosis. |
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