Research And Application Of The Regularity Of COPD Pathogenesis Of TCM

The main line of this study is to discover,verify and apply the regularity:on the basis of previous research,collect and analyze relevant literature(animal experiments,clinical trials and experience of famous doctors etc.)and combine with clinical experience,we conclude and discovery of the regularity of the pathogenesis of COPD in Chinese Medicine.The objectivity,scientific,validity and practicability of the regularity are proved through the relevant theories of traditional and modern medicine,clinical case investigation,animal experiment and cell experiment.Based on this regularity,two prescriptions are developed for the treatment of stable and acute phrase of COPD,respectively.According to relevant medical theory and the regularity,we propose the the hypothesis of “Long-term stimulation of chronic inflammation of COPD can induce malignant transformation of pleural mesothelial cells”.The inhibitory effect of “COPD-MPM formula” which based on the regularity and hypotheses proves objectivity and scientific of the regularity and the establishment of hypothesis at the same time.No.1 An exploratory study of the regularity of COPD pathogenesis of TCM in Clinical practice(case study)Objective:To prove the objectivity,scientificity and validity of the regularity by collecting and evaluating the data of COPD patients and to find out the problems in clinical practice at the same time.Methods: Through the medical record management system of affiliated hospital of Chengdu University of TCM,248 patients who are first diagnosed as acute exacerbation of COPD are included in our research.Results:1)The occurrence rate of deficiency,phlegm,blood stasis and heat are41.5%,75.0%,3.6%and 7.8%,respectively.The occurrence rate of the prescription of tonifying deficiency,treating phlegm(wet,water),activating blood and clearing heat are 41.5%,75.0%,3.6%and27.8%,respectively.2)Deficiency:(1)HGB:The rate of decrease of HGB is 44.35% in all patients,but only 7.7% diagnosed.;(2)Serum protein:Patients with the decreasing of TP,ALB and PA are all more than half of the total,but only 9.7% diagnosed;(3)Complicated diseases:Respiratory failure,hypoalbuminemia,anemia are the main diseases.(4)Tumor:There are 14 cases of tumor,of which lung cancer account for about 71.4%.3)(5)BMI value:The high-weight,normal-weight,low-weight are 63.4%,22%,14.5%,respectively.3)Phlegm(wet,water):(1)Infected pathogens:Mycoplasma pneumoniae,Candida albicans and Pseudomonas aeruginos are the main pathogens.(2)PAH:Accout for 41.1% and the level is mainly mild.(3)NT-Pro BNP: 48.5% have a high level,of which the average is10 times than the normal.4)Blood stasis:(1)Hypoxia: Respiratory failure account for71.0%,of which type II is 71%..(2)CT : 97.8% patients have emphysema and 47.2%have pleural thickening.(3)Pulmonary function: The large and small airways are severe,moderate(or severe)damaged,respectively.The pulmonary function grade is severe(41.9%)and moderate(30.2%).(4)Blood hypercoagulability: The D-Dimer,FDP and FIB are 3.5 times,4 times and 1.5 times higher than the normal in patients with high level,respectively.5)Heat:(1)Temperature:Most people”s heat are medium(42.8%)and low(39.3%).(2)Inflammation index:The average level of NEUT% is82.4% in patients with high level.The average of ESR,CRP and PCT are about 8 times,18 times and 3 times than the normal,respectively.Conclusions: 1)Deficiency,phlegm,blood stasis and heat are the main and common syndrome elements of COPD.The importance of pathogenesis of deficiency and stasis are ignored and tonifying and blood activating prescriptions should be more applied.2)Anemia,hypoproteinemia and low-weight,lots of concomitant disease;mixed opportunistic infections,airway hypersecretion and PAH/pulmonary heart disease;pulmonary function reduction,hypoxia and blood hypercoagulability;higher levels of hyperthermic inflammatory factors,which are respectively coincide with TCM syndrome factors deficiency,Phlegm(wet,water),blood stasis and heat.3)The regularity of pathogenesis of TCM about COPD is objective and scientific and deserves further research and application.NO.2 An exploratory study on the relationship between the Pathogenesis regularity and the treatment of COPD(Animal experiment)Objective: To explore the influence and effect of prescriptions which include stable and acute exacerbation prescription and which based on the regularity on COPD animals and to further explore the scientificity and validity of it.Methods:Fifty SD rats aged 6 weeks are randomly divided into Chinese(medicine)group,Chinese-western(medicine)group,normal group,model group and western(medicine)group.The rat model of COPD(AECOPD)is established by injecting MCT,smudging,hypoxia,instillation of elastase in the nasal cavity and cold stimulation.The Chinese group and the Chinese-western group are treated for about two weeks respectively with the stable stage prescription and acute exacerbation stage prescription,respectively.Chinese-western group and western group are given routine western medicine treatment.The normal and model group are given the same amount of normal saline.The administration time is 4 weeks.The curative effect and related evaluation indexes are observed.Results: 1)General situation of model mice:Their eyes is lackluster,fur is dry and dark and stool is loose.2)Food and water consuming:The rats in the Chinese-western group are close to the normal(P > 0.05)and higher than the model group rats(P < 0.05).3)Weight increment:The rats in Chinese-western group,Chinese group and western group are higher than that in model group(P < 0.05);4)Load swimming time:The rats in Chinese-western group and Chinese medicine group is longer than that of western group and model group,and the difference is statistically significant(P < 0.05).5)Albumin:There is no significant difference among groups(P > 0.05);6)HIF-1,PGF2α,LTB4:There is no significant difference among groups(P > 0.05).The mean value chart of HIF-1 shows that the model group is obviously lower than the normal group,but the Chinese-western medicine group is obviously higher than the normal group.7)Organ weight ratio:(1)Lung weight / body weight:There is no significant difference between each medication group and normal group(P > 0.05).The model group is higher than the normal group(P < 0.05).(2)Heart weight / body weight,brain weight / body weight:There is no significant difference among all the groups on the two indexes(P > 0.05).8)Alveolar number:Rats in Chinese-western group are more than that of model group,and the difference is statistically significant(P < 0.05).9)Respiratory membrane area:There is no significant difference between the Chinese-western group and the Chinese group compared with the normal group(P > 0.05)and the model group is larger than the normal(P < 0.05).10)Respiratory membrane thickness:The Chinese-western group is smaller than the model group,the difference is obviously statistically significant(P<0.05).11)Fibrosis indicators:(1)Percentage of fibrosis:The Chinese-western group is lower than the model group,the difference is statistically significant(P < 0.05).(2)OD value:Chinese-western group,Western group are lower than model group(P < 0.05).12)Gross appearance:(1)Appearance and activity:The overall health of the rats in the drug groups are improved and the Chinese-Western group is the most prominent.(2)Pathological specimen:On the surface of the lung of the model rats,there are white lesion areas,blood stasis clots and some of them could see the apex of the heart blunt and round and the appearance of the brain has no obvious change.13)Optical view(HE staining):(1)Lung:The alveolar epithelial cells necrosis and inflammatory cell infiltration are observed in the model group.The Chinese-western group is close to normal.(2)Heart:In the model group,the muscle fibers are disordered,partially denatured and broken.Chinese-western group is close to normal.(3)Cerebrum:There is no significant difference among the groups.14)Optical view(Masson staining):(1)Lung :There is obvious fibrosis in model group and mild fibrosis in Chinese-western group.(2)Heart:There is no obvious fibrosis change in all group.15)Electron microscope view:Mitochondrial swelling and crest rupture of type II epithelial cells can be seen in model group.The rats in the Chinese-western medicine group are close to normal.Conclusion:1)COPD model rats also have the pathogenesis of deficiency,phlegm(wet,water),stasis and heat.2)The objective,scientific and effective of the regularity have been proved in animal models of COPD.3)The combination the regularity based prescriptions and basic western therapy have synergistic effect,which can maximize the curative effect.NO.3 An exploratory study on the relationship between the regularity and MPM Therapy(Cell experiment)Objective:Application of COPD-Mesothelioma prescription based on the regularity to MPM cells and observation its therapeutic effect to further explore the scientificity,validity and practicability of it.At the same time,explore the possibility of the hypothesis“Chronic inflammatory stimulation from COPD disease causes malignant transformation of pleural mesothelial cells into MPM”.Methods: Purchase human mesothelioma cells for use.The experiment is divided into the control group,DMSO group(1% DMSO),TCM group(600 g/m L COPD-Mesothelioma prescription)and western medicine group(100mol/L methotrexate)which is used as the standard control.MTT and cell migration are detected in each group.Results:1)Proliferation inhibition:Compared with the control group and DMSO group,the OD value of TCM group and the western medicine group decreased after 12 h and 48 h treatment(the number of living cells decreased)(P < 0.05).After 12 hours of administration,the number of living cells in the TCM group decreased significantly and its effects reach the maximum after 24 hours.2)Migration inhibition:The number of migration cells in TCM group and western medicine group are significantly lower than that in the control group and DMSO group(P < 0.05).The migration cells in the western medicine group and TCM group are decreased.Conclusion:1)The inhibitory effects of proliferation,growth and migration of MPM by COPD-mesothelioma prescription which based on the regularity is obvious.2)The scientificity,validity and practicability of the regularity are confirmed.3)To some extent,the hypothesis mentioned above may be confirmed.