| Objective:To evaluate the relationships between Asthma and Allergic Rhinitis; Integrative evaluation of the therapeutic effects and predominance of Xiao Er Chuan Ke Ye combined with Cang Er Zi San;Explore and validate its functions of anti-asthma airway remodeling and prevention in irreversible airway obstruction,as well as its regulating mechanism to the main airway remodeling-related growth factor,inflammation medium and immunity.Research methods:1.Group division and Modeling:One hundred and thirty five male Wistar rats (aged 2-3 months) were randomly divided into nine groups with 15 rats each group:Blank group was intraperitoneal injected and with inhalation of saline. Asthma with airway remodeling model group was sensitized by intraperitoneal injection of fresh albumin and aluminum hydroxide solution on the first,eighth day respectively,from the fifteenth day on,introduced asthma attack by means of ultrasonic aerosol inhalation of albumin solution,once every two days, 20 minutes each time,and the inspired concentration are:the first,second week 1%;the third,fourth week 1.5%;the fifth,sixth week 2%;2.5%in the seventh,eighth week.2.Medication method:From the first day on give each group experimental interventions,once per day,until they are executed,a total of 70 days of interventions.Blank group,model group were given oral saline 10ml/kg; Western medicine group were given oral administration of dexamethasone 0.63mg/kg;Xiao Er Chuan Ke Ye low,medium and high-dose group was respectively given Xiao Er Chuan Ke Ye(Composed of Mahuang,Guizhi,Xixin,Danggui,Wuweizi, Zaoxiu etc.nine Chinese Herbs) oral administration 10g / kg,5g/kg, 2.5g/kg;Combination group low,medium and high-dose group was given respectively Xiao Er Chuan Ke Combination(Composed of Xiao Er Chuan Ke Ye and Cang Er Zi San,half each,Cang Er Zi San was composed of Cangerzi, Bohe,Baizi,Xinyi) 20g/kg,10g/kg,5g/kg.Result:1.General situations:1～2 minutes after inhaled albumin solution,Model group, Western Medicine group,Chuan Ke Ye group and Combination group rats began to appear symptoms of asthma attack,while blank group' s activities were quick and prompt,nothing unusual was detected.There were a total of five rats died of asthma attack:one in each of Chuan Ke Ye low-dose group and Combination low-dose group in the second sensitization stage;during asthma attack two died in Model group and one in Western group.Choose 10 each group,a total of 90 rats entered the final analysis.From the twelfth day on the rats in Western medicine group began to appear hyperactive,aggressive,bite others; from the twenty-first day on began to appear hairy and bloody stool.Till the end of the experiment,a total of six rats appeared bloody stool,while the Blank group,Model group,Chuan Ke Ye groups and Combination groups had no signs of above.2.Comparison of Allergic Rhinitis situation:On the twenty-first day,the allergic rhinitis average superimposed scoring in model group,western medicine group,Chuan Ke Ye group and combination group was significantly higher than blank group(P＜0.01);compare to model group,Chuan Ke Ye low-dose group was lower(P＜0.05),combination high-dose group was significantly lower (P＜0.01).On the seventieth day,compared to the blank group,the percentage of rats scoring above five in model group,Chuan Ke Ye low-dose group increased (P＜0.05);compared to the model group,the percentage of rats scoring above five in combination high-dose group decreased(P＜0.05).The average score in model group,western medicine group,Chuan Ke Ye groups and combination groups were significantly higher than blank group(P＜0.01);the average scoring in western medicine group,Chuan Ke Ye high-dose group and combination groups were lower than model group(P＜0.05).3.Comparison of asthma attack:On the fifteenth day,compared with the model group,the introducing time of asthma in combination high-dose group was significantly prolonged,the difference was significant(P＜0.01);compared with the western medicine group,the introducing time of asthma in combination high-dose group was prolonged,the difference was significant(P＜0.05);on the seventieth day of the experiment,compare with the model group,the introducing time of asthma in Western medicine group and Chuan Ke Ye high-dose group prolonged,the difference was significant(P＜0.05);combination medium, high-dose group significantly prolonged,the difference was significant(P＜0.01).Before and after self-comparison,Chuan Ke Ye medium dose group and combination medium group had significant difference(P＜0.05),Chuan Ke Ye high dose and combination high-dosegroup had significant difference(P＜0.01). Compare with combination high-dose group and Chuan Ke Ye high-dose group,the introducing time of asthma has been prolonged,the difference was significant (P＜0.05).On the seventieth day of the experiment,compared with the model group,the nodding breath frequency of combination low-dose group decreased, the difference was significant(P＜0.05);Western medicine group,Chuan Ke Ye medium,high-dose group and combination medium,high-dose decreased,the difference was significant(P＜0.01).4.Comparison of serum TGF-β1 levels:compare with the blank group,the serum TGF-β1 levels in model group significantly increased,the difference was significant(P＜0.01).Compared with model group,the level of TGF-β1 in western medicine group,all Chuan Ke Ye groups and combination groups had significantly decreased,the difference was significant(P＜0.01).5.Comparison of serum IFN-γ,IL-4 level and their ratio:compare with the blank group,the serum IFN-γlevel in model group significantly decreased, the difference was significant(P＜0.01);compare with the model group,the IFN-γlevels in Western medicine group,Chuan Ke Ye and combination groups significantly increased,the difference was significant(P＜0.01);compare with the western medicine group,the IFN-γlevels in Chuan Ke Ye high-dose group and combination medium,high-dose group significantly increased,the difference was significant(P＜0.01).Compare with the blank group,IL-4 levels in model group and Chuan Ke Ye low-dose group significantly increased,the difference was significant(P＜0.01);IL-4 levels of Western medicine group, Chuan Ke Ye medium,high dose group and combination low,medium dose increased, the difference was significant(P＜0.05).Compared with model group,IL-4 level of western medicine group,all Chuan Ke Ye groups and combination low, medium dose group decreased,the difference was significant(P＜0.05); combination high-dose group IL-4 levels significantly decreased,the difference was significant(P＜0.01);compare with the western medicine group, level of IL-4 in combination high-dose group decreased,the difference was significant(P＜0.05).Compare with Chuan Ke Ye high dose group,IL-4 levels of combination high dose group decreased,the difference was significant(P＜0.05).Compare with the blank group,serum IFN -γ/IL-4 ratio of model group significantly decreased,the difference was significant(P＜0.01);serum IFN -γ/IL-4 ratio of Chuan Ke Ye high-dose group and combination medium,high dose group increase significantly,the difference was significant(P＜0.01); Compared with model group,IFN-γ/IL-4 radio of western medicine group,all Chuan Ke Ye and combination groups significantly increased,the difference was significant(P＜0.01);compare with the western medicine group, IFN-γ/IL-4 radio of Chuan KeYe high-dose group and combination medium, high-dose group significantly increased,the difference was significant(P＜0.01).6.Comparison of serum ECP level:Compare with blank group,serum ECP levels of model group significantly increased,the difference was significant(P＜0.01);Compared with model group,ECP level of western medicine group,Chuan Ke Ye high-dose group and combination high-dose group decreased,the difference was significant(P＜0.05).7.Comparison of weight increase:After 70 days compare the blank group, model group,all Chuan Ke Ye and combination groups,Western Medicine group significantly gained weight,the difference was significant(P＜0.01).8.Bronchial morphological observation:The tracheal epithelia of model group rats edema,fall off and the airway wall is incomplete;a small amount of inflammatory exudates,eosinophils,lymphocytes,maerophages can be seen in the cavity;local bronchial submucosal edema,airway wall and airway smooth muscle obviously thicken,luminal stenosis;under high-power microscope fibrosis changes can be observed in the airway sub-epithelial cells,under the airway epithelium a large number of spindle-shaped fibroblasts can be found, myofibroblast can be observed in the smooth muscle layer.Number of goblet cells,secretion can be seen in the lumen.Airway inflammation in Western medicine group,all Chuan Ke Ye and combination groups had been reduced to disappear.Number of goblet cells decreased,both airway smooth muscle thickening and luminal stenosis have been reduced,under high-power microscope can observe the fiber cells decrease.Compared with the blank group,the airway wall thickness of model group obviously more thickening,the difference was significant(P＜0.01);Compared with model group,the airway wall thickness of western medicine group,all Chuan Ke Ye and combination groups are less thickening,the difference was significant(P＜0.01).Conclusions:1.According to the clinical symptoms,laboratory examinations and bronchial pathology observations,the models of Asthma with airway remodeling had been successfully made by means of ovalbumin and aluminum hydroxide solution sensitization and ovalbumin solution introducing asthma.2.Allergic rhinitis is not only the important accompanied factor during the occurrence and development of asthma,but also has close relationship with the development of airway remodeling.During the remission of asthma,the occurrence of allergic rhinitis in Chuan Ke Ye Group decreased,we presume allergic rhinitis and asthma have the same pathogenesis,when treating asthma with Xiao Er Chuan Ke Ye the occurrence and development of allergic rhinitis have been cut off at the same time,thus the radio of allergic rhinitis and symptoms scoring decreased too.The simultaneity use of Xiao Er Chuan Ke Ye and Cang Er Zi San intervening asthma and allergic rhinitis,comparing simply use Xiao Er Chuan Ke Ye,has the predominance in prolonging time of introducing asthma and reducing the frequency of nodding breathe,which indicated that the treatment of allergic rhinitis has great importance in asthma control(time of introducing rat asthma) and lessen the degree of asthma(frequency of rat nodding breath).3,The combination high-dose group has better therapeutic effect than dexamethasone group(western medicine group),all Chuan Ke Ye groups and combination low,medium group in the prevention and control of allergic rhinitis symptoms,reduced airway hyper responsiveness,while in improving breath difficulties combination high-dose group has similar effect with western medicine group,and better effect than all Chuan Ke Ye groups and combination low,medium group.Its efficacy increased with the prolonging of treatment time,but fewer side effects,which makes the application safer and more reliable.4,Xiao Er Chuan Ke Ye combining with Cang Er Zi San can obviously improve the pathological changes in rats with bronchial airway remodeling,reducing the serum TGF-β1,IL-4,ECP levels,increasing the level of serum IFN-γand the imbalance IFN-γ/ IL-4 ratio.We can presume the anti-airway remodeling effects of Xiao Er Chuan Ke Ye combining with Cang Er Zi San have close relationships with its regulation role to the cytokines and inflammatory cells, improving immunity function and thus reducing the inflammatory response.
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