A Study Of Effect Rate Of Expelling Wind And Releasing Lung Fomula To Cure CVA And Its Relating Effect To Airway Neurogenic Inflammation

Back GroundCough is a protective action that can effectively clear the respiratory secre tions and the harmful substances that are blocked in the airway.However,du e to individual differences or the impaction of serious illness,the cough becom es frequent,intense,uncontrollable,affecting people to talk or sleep.Especiall y,the long-time cough do seriously bad to the patients in physical,mental and economic aspect.In the outpatient service,there is no clear diagnosis on the patients,given a large number of empirical use of antibiotics and antitussive drugs.This phenomenon leads to the heavy medical and health expenditures of family and even the country.In the department of respiration clinic,10%-38%of patients is diagnosed with unexplained chronic cough,and prevalence rate of chronic cough is higher than 3.3%.In recent years,due to environmental pollution,the incidence and visiting rate of cough in China is increasing.Chro nic cough has been paid more and more attention,requiring the classification a nd targeted treatment.From neuroanatomy perspective,Irwin systematically dis cussed cough,making people aware of that chronic cough is unique in etiolog y and pathology from traditional cough after infection,in the 1980s.The stud y of this type of cough has become a hot topic.Cough variant asthma in the chronic cough accounts for 33.3%,which is firstly discovered by Glauser in 1972.This disease has relations with allergic sensitization,and its pathophysio logyical characteristics is similar with typical asthma,such as,airway inflamma tion,airway hyperresponsiveness.It is believed that the increased of airway high reactivity is the core of c ough caused by any reason,especially chronic cough.Airway abnormally incr easing response to normal stimulation results in frequent cough and prolonged healing.Modern medichine is generally believed that the airway inflammation is the main mechanism of airway hypperresponsiveness,and there are complex interactions between airway inflamation and the nerve endings in airway which conact the central and peripheral nervous system.It has been proved that the sensory nerve in the airway and its secreted nerve factors may be directly invo lved in the formation of airway inflammation.Which,we called airway neuro genic inflammation.The typical airway hyperresponsiveness disease is asthma,and,NGF and its receptor are high expressed in asthma.The airway neuroge nic inflammation is an important cause of increased cough sensitivity and prolo nged cough.Recently,tyrosine protein kinase membraine receptor signal transd uction pathway(Ras/MAPK pathway)which NGF acts on and its downstream factors,such as,substance P,which play biological effect have attracted more and more attention.Traditional Chinese Medicine has a long history of knowledge and treatme nt of cough,and has a unique understanding of cough,recognized cough as a single diagnosis.The Inner Canon of Huangdi says "all the five internal orga ns make people cough";Valuable Prescriptions for Emergencies proposed ten types cough classification method;Zhang Jingyue of Ming Dynasty divided cou gh into two major categories of exogenous and internal injuries.Which impro ved clinical practice.Exogenous fator refers to the six evils invaded the lung s,such as,wind,cold,heat,dampness,dryness,fire.Internal injury refers to weakness of the viscera,disfunction,and forming syndrome,such as,phlegmy wetness aggregating lung,liver-fire invading lung and kidney deficiency.TCM has a better curative effect and more experience in improving symptoms,espe cially for airway hyperresponsiveness of intractable cough.CVA has a lot of symptoms,such as,dry cough,throat itching,the paroxysmal and irritating cou hg,induction by speech,dust,hot and cold air,cough at night and long cours e.All the symptoms above belong to the TCM "wind cough".TCM has a 1 ong history of recognition and treatment of "wind cough".With the increasing of clinical research on the treatment of CVA in recent years,"wind cough" pl ay the key role.Professor Shi Liqing recognized that "incubative wind in lun g" is the critical pattern of syndrome in many,and get good curative results o f treating CVA with "expelling wind and releasing lung fomula".Clinical Research(1)Research PurposeThrough the observation and comparison of 72 cases of patients with CVA"incubative wind in long" pattern of syndrome,respectively,clarifying the e ffect of the treatments of "expelling wind and releasing lung fomula" and p lacebo.Inorder to clarify the effect of the fomula in the treatment of CV A scientifically and objectively.Comparing with placebo,studying the curati ve result of TCM,and evaluating the clinical application of "incubative win d in lung" theory in the treatment of CVA.(2)Research MethodFinding 70 patients of CVA with "incubative wind in lung",choosing rando mized controlled trial method.The 40 patients take "expelling wind and re leasing lung fomula" as treatment group,and 32 patients takes placebo as c ontrol group.Observe the change of two groups of patients' subjective ord er of cough,times of cough,degree of cough,pharyngeal itching,short of breath and expectoration on the day before treating and 14th day after the t reatment.Compare the differences in cough scores between two groups,an d analyzed them using the statistical method.(3)Research Results1.General situation:1)Number:80 cases in group,treatment group losed 1 case caused by irregula r medication;Placebo group losed 7 cases caused by stoping taking medicin e.2)Age:31 young people,20 middle-aged people.17 light old people.4 o ld people;3)Gender:51 female,21 male;4)The patients diagnosed of aller gic rhinitis:20 cases,accounting for 27.8%.2."Incubative wind in lung" syndrome score:Before treatment,there is no diffe rence between two groups(P>0.05);After treatment,the score of treatment g oup is significantly lower than before treatment(P<0.01);After treatment,the score of treatment group is significantly lower than placebo group(P<0.01).3.Cough visual score:Before treatment,there is no difference between two gro ups(P>0.05);After treatment,the score of treatment goup is significantly lo wer than before treatment(P<0.01);After treatment,the score of treatment gr oup is significantly lower than placebo group(P<0.01).4.Cough symptom score:Before treatment,there is no difference between two groups(P>0.05);After treatment,the score of treatment goup is significantly lower than before treatment(P<0.01);After treatment,the score of treatment group is significantly lower than placebo group(P<0.01).5.Effective rate based on cough symptom score:Effective rate of "expelling wi nd and dispersing lung fomula" is 62.5%,and effective rate of placebo is 21.9%.The effective rate of "Expelling wind and dispersing lung fomula" is significantly higher than placebo group(P<0.01).6.Cough relief time:The patients who responded to "expelling wind and disper sing lung fomula" is 25,and the average cough reduce time is 3.24± 1.01 day s.(4)Conclusion1.It has been obviously improved by "expelling wind and dispersing lung fomula" that "Incubative wind in lung" patern of syndrome,felling of cough a nd symptoms of cough both day and night,better than placebo.2.The placeb o plays a little role in feeling of cough,and it makes the patients feel worse.Placebo does no good to symptoms of cough both day nand night.3.The e ffective rate of fomula is 62.5%,far higher than placebo.5.The onset time of fomula treating CVA is 3.24±1.01 days.Experimental Study(1)Research PurposeGive the SPF Hartley guinea pigs by gavage with normal saline,Chinese h erbal decoction,and extract the serum containing drug.Culture human bronchia 1 epithelial cells with the serum containing drug,to observe the influence of"expelling wind and dispersing lung fomula" on signal transduction of airway neurogenic inflammation.Investigate the role of Ras-Raf-MAPK signal pathwa y in airway eurogenic inflammation and cough hypersensitivity,and substance basis for the treatment of neurogenic inflammation of the airways by "expellin g wind and dispersing lung fomula".(2)Research MethodGive the SPF Hartley guinea pigs by gavage with normal saline,Asmeton or three doses of "expelling wing and dispersing lung fomula"(high dose,midd le dose,low dose)for one week,and take the drug containing serum from art ery.Trough in-vitro experiment,observe the influence of different kinds of ser ums on related factors in Ras/Raf/MAPKK/MAPK/C-fos signal passway.(3)Research Results1.Cell proliferation,apoptosis and cell cycle:The effect of PD98059 and Asmeton serum on the inhibition of NGF is signifi cant.The high dose of "expelling wind and dispersing lung fomula"has a cert ain inhibition function,and the inhibition is in a dose dependent manner.PD98059 alone has no effect on cell proliferation.The results of apoptosis of cell s shows:only the apoptosis rate of group of PD98059 is more than 10%,and other groups are all less than 10%.Cell cycle test shows that the cell cycle of eache group is approximately the same.2.Western-BlotNK1R:The expression of NK1R protein in the medium dose and low dose of Chinese medicine serum group is lower than the model group.And the inhibiti on of NK1R caused by medium dose group is the best.Pan-Ras:The expression of Pan-Ras protein in the medium dose group is lowe r than that in the model group.C-fos:The expression of C-fos protein in the medium dose group and low dos e group is lower than that in the model group.And,the inhibition of C-fos protein in the medium dose group is significantly lower than that in the low d ose group.P-Erk1/2:The expressions of P-Erkl/2 protein in Asmeton group,three doses o f Chinese medicine are lower than the model group.And,P-Erkl/2 protein in the Asmeton group and high dose of Chinese medicine decrease significantly.3.RT-PCRPan-Ras:Large,medium and low doses of Chinese medicine can reduce the ge netic expression of Pan-Ras(P<0.01),and medium and low doses are more obv ious(P<0.01),Asmeton cannot reduce the genetic expression of Pan-Ras(P>0.05).C-fos:Asmeton and Chinese medicine can significantly reduce the genetic expr ession of C-fos(P<0.01).And,the effect of Chinese medicine is superior to As meton(P<0.01).The inhibitive effect of medium dose of Chinese medicine is t he most(P<0.05).NK1R:Asmeton and three does of Chinese medicine can significantly inhibit t he genetic expression of NK1R(P<0.01).The effect of high dose and medium dose of Chinese medicine are better than Asmeton(P<0.01).And,medium dos e is obviously better than the other two doses(P<0.01).(4)Conclusion1.NGF plays an important role in human airway epithelial cells through the a ctivation of Ras/Raf/MAPK pathway and the expression of related factors.All these show that the model preparation is successful.Chinese medicine and Asmeton can promote the expression of protein and genetic expression of Ras/Raf/MAPK pathway related factors in different degrees.And,the m edium dose of Chinese medicine is better than the other two doses.