Study On ECP,IgE,FEV₁ And Gene Polymorphism Of β₂-AR,IL-4,IL-13 And Prethrombotic Seate In Bronchial Asthmatic Patients With Abnormal Savda

Object:With the rapid development of modern medicine, the development of modern immunology, molecular biology contributed a lot to the etiology, pathogenesis, immunology, diagnosis and treatment of asthma. As far as the complexity of asthma concerned, its pathogenesis is still not clear enough. It is generally believed that, asthma is a chronic non-specific inflammation. A variety of cells and cell groups participate in the chronic airway inflammation. Innate congenital specialty and acquired allergic significance are the basis of asthmatic development. The imbalance between the nerves and their receptors which regulates the function of bronchitis may also be related to the formation of asthma. The main treatment methods of asthma are the usage of glucocorticoid, expansion of tracheal and leukotriene regulating agents. Although such treatment methods are effective in controlling of asthma, they cannot significantly reduce the mortality, cannot completely eradicate the disease itself. So in order to explore the pathogenesis of asthma and to seek an effective treatment method is the challenge that we are currently facing. Looking for a treatment method from the Traditional Chinese Medicine has even greater significance.Being an indispensable part of Traditional Chinese Medicine, Uyghur Medicine has its unique recognition and effective treatments for asthma. Asthma is divided asthma with abnormal Kan, asthma with abnormal Balgam, asthma with abnormal Sapra and asthma with abnormal Savda in Uyghur Medicine. In the previous studies, our research group discovered that, the asthmatic patients with abnormal Savda have the oldest age, most severe symptoms and most complex pathogenesis of asthma. In an asthma attack, compared to the other types of asthma in Uyghur Medicine, the value of CDllb, CDllb/CDl8 and rate of lymphocyte apoptosis in asthmatic patients with abnormal Savda was the highest, the value of CS, ACTH and CRH was the lowest in asthmatic patients with abnormal Savda. From above results, we assume that immune dysfunction, reduced endogenous cortisol and infection are the probable factors which largely contribute to the formation of asthma with abnormal Savda. We also discovered that there is a correlation ship in asthma with abnormal Savda in Uyghur Medicine, deficieacy asthma of traditional chinese medicine and the severe asthma in Western medicine. There is commonness in the level of CDllb/CDl8, lymphocyte apoptosis and the level of endogenous cortisol in these three types of asthma. There is a significant change in the metabolic group model between asthma with abnormal Savda and the other types of asthma in Uyghur Medicine.Based on the results of previous research, this study will discuss the changes of ECP,T-IgE,S-IgE,FEV₁,CD41,CD62P,ET-1,t-PA,PAI-1,FIB,APTT,PT,TT in asthma with abnormal Savda and the relationship betweenβ₂-AR IL-4, IL-13, gene polymorphism and the asthma with abnormal Savda. By studying the genetic susceptibility of asthmatic patients with abnormal Savda and analyzing whether the above indicators can be used as part of the macro diagnostic indexes of asthma, this study will try to grasp more accuracy in the diagnosis of asthma and making the diagnosis even more objective.at the same time., this study will also look for the probable targets of treating asthma with abnormal Savda in Uyghur Medicine.Materials and MethodsPatients:, There were 76 cases of asthmatic Uyghur patients in first and second group who were hospitalized from November 2006 to June 2007 in Hotan district of Xinjiang. There were 67 cases of asthmatic patients in the third group who were hospitalized from February 2006 to October 2006 in Traditional Chinese Medicine hospital in Urumqi. All patients were diagnosed according to the criteria of Uyghur Medicine and the Western medicine asthma diagnosis. 89 cases of healthy individuals,they have all been checked to make sure that they do not have hypertension, diabetes or other heart, liver, kidney and blood diseases. All individuals have been checked for following indicators: ECP, T-IgE, S-IgE were tested by using immuno fluorescence detection, FEV₁ was checked by using lung function testing machine,β₂-AR, IL-4, IL-13, gene polymorphism were measured by polymerase chain reaction method. The expression of CD62p on platelets, the level of plasma tissue plasminogen activator (t-PA)and its inhibiter(PAI-1), the level of endothelin-1(ET-1), Activated partial thromboplastin time (APTT), Fibrinogen ( FIB), Prothrombin time ( PT) and Thrombin time (TT) were tested by using Flow Cytometer, ELASA method, radioimmunoassay method and auto coagulometer. Statistical analysis: SPSS11.5 was used in the study. The data was expressed as means±standard deviation (SD). Statistical significance of a comparison was determined by using ANOVA. The difference between means was considered to be statistically significant if p<0.05.Results:1)Compared to normal control group, level of serum ECP was significantly changed in asthma with abnormal Savda and asthma with non abnormal Savda groups(P<0.01),the level of ECP was significantly higher in asthma with abnormal Savda group than that of the asthma with non abnormal Savda group and the normal control group(P<0.01). Compared to normal control group, level of serum T-IgE was significantly changed in asthma with abnormal Savda and asthma with non abnormal Savda groups(P<0.01),the level of T-IgE was significantly higher in asthma with abnormal Savda group and asthma with non abnormal Savda group than that of the normal control group(P<0.01). The level of T-IgE had no statistical difference between asthma with abnormal Savda and asthma with non abnormal Savda group(P>0.05)。Compared to normal control group, level of serum S-IgE significantly changed in asthma with abnormal Savda and asthma with non abnormal Savda groups(P<0.01),the level of S-IgE was significantly higher in asthma with abnormal Savda group and asthma with non abnormal Savda group than that of the normal control group(P<0.01),The level of S-IgE had no statistical difference between asthma with abnormal Savda and asthma with non abnormal Savda group(P>0.05). Compared to normal control group, level of FEV₁ was significantly changed in asthma with abnormal Savda and asthma with non abnormal Savda groups(P<0.01), the level of FEV₁ was significantly decreased in asthma with abnormal Savda and asthma with non abnormal Savda group than that of the normal control group(P<0.01).2)Asthma with abnormal Savdaβ₂-AR gene polymorphism in 16 points (Gly / Gly) homozygous genotype frequency distribution was significantly higher than that of the asthma with non abnormal Savda group and the normal control group(P<0.01)。There was no statistical difference inβ₂-AR gene polymorphism in 16 points (Gly / Gly) homozygous genotype distribution frequency between these three groups(P>0.05). There was no statistical difference inβ₂-AR gene 27 points genotype frequency distributions and allele frequency distribution between these three groups(P>0.05). Compared to normal control group, IL-4 gene promoter -589 (C / T) sites CT genotype frequency distribution was significantly changed in asthma with abnormal Savda and asthma with non abnormal Savda groups(P<0.01)(P<0.01). IL-4 gene promoter -589 (C / T) sites CT genotype frequency distribution was significantly higher in asthma with abnormal Savda group than that of the asthma with non abnormal Savda group and the normal control group(P<0.01). IL-4 gene promoter -589 (C / T) sites CT genotype frequency distribution was significantly higher in asthma with non abnormal Savda group than that of the normal control group(P<0.05). There was no statistical difference in CC, TT genotype and allele frequency distribution between these three groups(P>0.05).IL-13 gene polymorphism loci intron 3 +1923 in asthma with abnormal Savda TT, TC genotype frequency distribution was significantly higher than that of the asthma with non abnormal Savda group and the normal control group(P<0.01),asthma with non abnormal Savda group TT, TC genotype frequency distribution was significantly higher than that of the normal control group(P<0.05),CC genotype frequency distribution in normal control group was significantly higher than that of the asthma with abnormal Savda group (P<0.05)and asthma with non abnormal Savda group(P<0.01). T allele frequency distribution of this site in asthma with abnormal Savda group was significantly higher than that of the normal control group(P<0.01),C allele frequency distribution of this site in normal control group was significantly higher than that of the asthma with abnormal Savda group(P<0.05). There was no statistical difference in IL-13 gene loci +2044 genotype frequency distributions and allele frequency distribution between these three groups(P>0.05).3)Compared to normal control group, there was no significance on the expression of asthma with abnormal Savda group and asthma with non abnormal Savda group(P>0.05);the expression of CD62P in all three groups(P<0.05),among them the expression of CD62P in asthma with abnormal Savda group was significantly higher than that of the asthma with non abnormal Savda group(P<0.05). Compared to normal control group, level of serum ET-1 was significantly higher in asthma with abnormal Savda and asthma with non abnormal Savda groups(P<0.05),the level of ET-1 was significantly higher in asthma with abnormal Savda group than that of the asthma with non abnormal Savda group and the normal control group(P<0.01). Compared to normal control group, level of plasma t-PA was significantly lower in asthma with abnormal Savda and asthma with non abnormal Savda groups(P<0.05);Compared to normal control group, level of serum PAI-1 was significantly higher in asthma with abnormal Savda and asthma with non abnormal Savda groups(P<0.05). Compared to normal control group, level of plasma FIB was significantly higher in asthma with abnormal Savda and asthma with non abnormal Savda groups(P<0.05), the level of plasma FIB was significantly higher in asthma with abnormal Savda group than that of the asthma with non abnormal Savda group and the normal control group. Compared to normal control group, level of APTT,PTwas significantly shortened in asthma with abnormal Savda and asthma with non abnormal Savda groups (P<0.05); There was no significance on TT between these three groups(P>0.05).Conclusion:1)ECP is a specific indicator of eosinophil activity, it reflects the degree of airway inflammation in the development. IgE-mediated allergic reaction is one of the main reasons of airway chronic inflammatory reaction. High level of T-IgE,S-IgE is not only the main recognition factors of atopic disease but also the main characteristic of airway chronic inflammation. The result of this study showed that, the level of serum ECP,T-IgE and S-IgE was significantly higher in asthmatic patients with abnormal Savda. From this result we assume that the high level of serum ECP,T-IgE and S-IgE might be the potential deciding factor if asthma with abnormal Savda. Therefore, judgement and assessment of these factors might have certain clinical significance in assessing the activity of asthma with abnormal Savda .2)FEV₁ is related to the small airway resistance. FEV₁ is a reliable indicator of the degree and severity of airway obstruction. Decreased FEV₁ indicates the existence of airway obstruction. Our research result showed that the level of FEV₁ was significantly lower in asthmatic patients with abnormal Savda than that of the asthmatic patients with non abnormal Savda, indicates that airway obstruction is most obvious in asthmatic patients with abnormal Savda.3)Individuals who haveβ₂-AR gene with 16 points glycine / glycine (Gly / Gly) homozygotes have a higher risk in developing asthma with abnormal Savda compared to individual who do not have it. We assume that when glycine arginine (Gly / Arg) heterozygous in individuals mutates to arginine, glycine, these individuals will have a higher risk in developing asthma with abnormal Savda. Gly/Gly genotype might be the inherent risk factor of asthma with abnormal Savda. There might be a correlation between theβ₂-AR gene polymorphism with 16 loci and asthma with abnormal Savda. 4)Individuals who have IL-4 gene promoter -589 (C/T) site with CT heterozygous genotype is related to the susceptibility of asthma with abnormal Savda, implies that IL-4 gene promoter -589 (C/T) site with CT polymorphism maybe an important candidate gene of asthma with abnormal Savda susceptibility.5)IL-13intron 3 +1923 siteand TT and TC gene may be related to the pathogeneses of asthma with abnormal Savda. It is the susceptibility gene of asthma with abnormal Savda. The T allele of this site may be the susceptibility gene of asthma with abnormal Savda, C allele of this site may be the resistance gene of asthma with abnormal Savda. Individual With the T allele who are stimulated by environmental factors, such as repeated allergen exposure, long-term living in seriously polluted environment, are the ones who will have a higher chance of developing asthma with abnormal Savda than those with C allele. Therefore, individuals who have IL-13 intron3 +1923 site with T allele may be the important focus groups of asthma with abnormal Savda prevention in peacekeeping and medical abnormal biliary asthma prevention in Uyghur Medicine.6)Studies found that prethromboitic state may be one of the pathological basis of asthma with abnormal Savda, and may also be pathogenic factors. There is platelet, vascular endothelial cells, blood coagulation and fibrinolytic function disorder , and in asthmatic patients with abnormal Savda, expressed in the activation of platelets, vascular endothelial cell damage, increased blood viscosity and reduced fibrinolytic function. Above results imply asthmatic patients with abnormal Savda are in a prothrombotic state, which is more prominent than asthmatic patients with non-abnormal Savda.In short, the pathogenesis of asthma with abnormal Savda in Uyghur Medicine is heavier and more complex. Combined with the results of previous studies, we believe that in the diagnosis of asthma with abnormal Savda, while complying to the diagnostic methods in Uyghur Medicine, it is also important to consider the patient's immune dysfunction, endogenous cortisol decrease, the changes of serum ECP, T-IgE, S-IgE, FEV₁ lung function andβ₂-AR, IL-4, IL-13 gene polymorphism and CD62P, t-PA, PAI-1, FIB , APTT, PT. We should also consider these indicators as the micro indicators of asthma with abnormal Savda. These results will provide a new target for treating asthma with abnormal Savda in Uyghur Medicine, also it provides a thingking for the development and progresss of combined Uyghur, Western Medicine treatment of asthma.