The Effects Of Glucosidorum Trpterygll Totorum Combining With SERETIDE In Asthma Treatment And Its The Mechanism

Aims and MeaningAsthma is a common chronic and nonspecific inflammatory disease of airways which multi-inflammatory cells, cytokines and inflammatory mediates were involved. Its main clinical manifestation includes recurrent breathing,chest tightness,cough and decompensation. In recent years, studies have shown that a variety of cells with theirs components involved in the formation of inflammation of airway in asthma, providing the important basis for anti-inflammatory treatment strategies. Inhaling glucocorticoids helps to inhibit a variety of inflammatory factors which include cytokines, inflammatory enzymes , adhesion molecules, chemokines and inflammatory mediators and so forth. The long-actingβ2 receptor agonist(LABA) has the obvious effect of dilating bronchus, reducing airway resistance and anti-inflammatory. Theβ2 receptor agonist might increases the level of intracellular cAMP and activate protein kinase A (PKA) and mitogen-activated protein kinase (MAPK), which speed up the nuclear transfer of glucocorticoid receptor. Glucocorticoid make theβ2 receptor hardly phosphorylated by inhibiting the GRK-2, which keep activity of theβ2 receptor. The mutual complementationand synergistic effect consist in the glucocorticoid and theβ2 receptor agonistprompt appearance of SERETIDE (salmeterol xinafoate and fluticasonepropionate). Glucosidorum Trpterygll Totorum(TP)which has immunosuppressiveeffect is usually used as a Chinese medicine, and is considered having therapeuticaction like glucocorticoid therefore, is used in chidlhood rheumatoid disease,dropsical nephritis and NNS. It has a better curative effect in the control ofrefractoriness asthma.The research is designed to compare the TP combining with SERETIDE withSERETIDE in clinical therapeutic effect for asthma and investigate its mechanismto providing experimental basis for treating asthma.The Contents1.Observation of clinical effect and the safety of TP joint SERETIDE in asthmatreatment, and compared with SERETIDE inhaled alone.2.Measuring number of CD₄⁺CD₂₅⁺Treg,Foxp3⁺ cells and the serous level of IL-4,IL-5,IL-10,IFN-γ,TGF-βin blood from the asthmatic patients who receivedtreatment with TP joint SERETIDE or SERETIDE alone.The Selection of asthma patients and Grouping42 asthma outpatients from Xi'Jing hospital (from march, 2008 to June, 2008)were randomly divided into two groups: SERETIDE inhaled alone group(A group,n=21, mean age37.5±12.1), TP joint SERETIDE group (B group, n=21,mean age35.0±11.7). There were comparable gender, age and asthma history between thetwo groups of patients(p>0.05), and all subjects had mornal liver function assay.The Drug UsageTaking TP 0.3-0.5 mg/kg, thrice per day, after meal.Inhalation of SERETIDE (50μg /250μg), twice per day, rinsing the mouth after inhaling.The Methods of ResearchCollecting the basic information (including lung function and ACQ score) and venous blood from 42 asthma patients in the morning, divides into A and B randomly. The experiment was 3 months, scheduled 1 visit per month. Compare the changes fore-and-aft the treatment in indexes as follows:(1) The percents of CD₄⁺CD₂₅⁺ Treg cell and Foxp3⁺ cells in CD₄⁺T cell (FCM);(2) The serous level of IL-4,IL-5,IFN-γ,IL-10,TGF-β(ELISA);(3) The clinic cure effects: evaluate effect according to ACQ. Evaluation criteria: <0.75, complete control; > 1.5, uncontrol; 0.75-1.5 favorable control;(4) The changes of liver function.Applying the SPSS_13.0 (a kind of statistic software) to analyze and deal with data. Comparing dates of two groups (A and B) matched by t-test, and intergroup by t-test. The results were expressed by ways of mean±standard deviation. Linear correlation Analyzing was used in analyzing relationship between CD₄⁺CD₂₅⁺ Treg cells in venous blood and cytokine in seru. when p< 0. 05, statistical significance in differences.The Results1. The efficiency of treatment.Group A : Of 21 patients, 12 complete control, 7 favorable control, 2 uncontrol, the total efficiency was 90%;Group B: Of 21 patients , 18 complete control, 2 favorable control, 1 uncontrol, the total efficiency was 95%.The total efficiency of the two groups had no significant difference, but the complete control rate in Group B was significantly higher than Group A (p<0.05). Refer to Table 1. 2. The changes of pulmonary function fore-and-aft the treatment in two groups. There are no significant difference in FEV₁% Pred And PEF% Pred, between two groups before the treatment (p> 0.05, respectively,). In two group, the improvement of the above-mentioned indicators was significant after treatment (p <0.05, all.), but the increasing range of FEV₁ and PEF in Group B is exceeds in Group A,( Refer to Table 2). ACQ (the average score ) of two groups are improved after the treatment, the difference has significant (p <0.05), but more pronounced improvement in Group B ( Refer to Table 2 ).3. The changes of CD₄⁺CD₂₅⁺Treg and Foxp3⁺ cells fore-and-aft the treatment. Measuring the changes of peripheral blood CD4⁺CD25⁺ Treg and Foxp3⁺cells in asthma patients fore-and-aft the treatment ( Refer to Table 3). In two groups, the percentages of CD4⁺CD25⁺ Treg and Foxp3⁺cells in CD4⁺cells were low and there were no differences (p> 0.05). The percentages were increased in two groups after the treatment, but the increase and the difference in Group B is more clear (p<0.05).4. The changes of serum cytokine level fore-and-aft the treatment. The changes of cytokine in serum in two groups fore-and-aft the treatment (Refer to Table 4). The concentration of the IL-4, 5 was significantly lowered (p<0.05, all.) in two groups after the treatment; However, the level reduced distinctly in group B (p<0.05, all.). The IFN-γlevels are significantly increased after treatment, particularly in Group B (p<0.05). The IL-10, TGF-βlevel are increased after treatment in Group B (p<0.05, all.), but the difference in Group Ais not obvious(p> 0.05). 5. Analysing the relativity between CD₄⁺CD₂₅⁺ Treg percentage of peripheral blood and serum cytokines in two groups.Through the relativity analysis of spearman's, the percentage of CD₄⁺CD₂₅⁺ Treg was positively correlated with that of Foxp3⁺ cells in CD₄⁺ T (r= 0.698). CD₄⁺CD₂₅⁺ Treg cells and Foxp3⁺ cells in two groups after treatment were significantly increased with the increase of the IL-10, TGF-β, IFN-γcytokine expression(r=0.474); but were negatively correlated with the serous level of IL-4, 5 (r= -0.542).The Conclusions1. The therapeutic efficacy of TP joint SERETIDE for chronic asthma is superior tothe simple SERETIDE inhalation;2. TP is capable of inducing the differentiation of CD₄⁺CD₂₅⁺ Treg, reducing theIL-4, 5 serum levels and enhancing IFN-γ, IL-10 and TGF-β1, restoring the dynamic balance of Th1/Th2 cytokines.