| Bronchial asthma is one of the common chronic respiratory diseases.Its clinical symptoms are asthma and chest tightness.Its pathogenesis is related to airway inflammation.airway hyperresponsiveness,airway mucus hypersecretion and airway remodeling.In recent years,the incidence of bronchial asthma has gradually increased,seriously affecting people’s daily life.Chinese medicine has a long history in the treatment of asthma,and has rich clinical experience.Guishaozichuan Granules is composed of 11 traditional Chinese medicines,such as Astragalus membranaceus,Cinnamon Twig and Paeonia Alba.It has the functions of invigorating spleen and benefiting lung,reducing Qi and relieving asthma.It is suitable for asthma caused by lung-spleen deficiency and impairment of dispersing and descending function of the lung.Previous studies have shown that the compound can significantly improve the clinical symptoms and signs of patients with bronchial asthma.In this study,ovalbumin-induced bronchial asthma rat model was used to observe the effects of Guishaozichuan Granules on airway responsiveness by detecting airway resistance and dynamic compliance.The effects of Guishaozichuan Granules on airway inflammation were observed by detecting IgE,inflammatory cytokines,EOS(eosinophils)and WBC(leucocytes)in bronchoalveolar lavage fluid(BALF)and lung histopathology.Also the effect of compound on airway mucus secretion was studied by MUC5AC/EGFR signaling pathway,in order to provide reference for its further clinical application.1 Intervention effect of Guishaozichuan Granules on ovalbumin-induced asthma in ratsObjective:To observe the intervention effect of Guishaozichuan Granules on airway hyperresponsiveness and airway inflammation in ovalbumin-induced bronchial asthma rats.Methods:SD rats were randomly divided into 7 groups:normal group,model group,Guishaozichuan Granules high dose group(2.68 g/kg),Guishaozichuan Granules medium dose group(1.34 g/kg),Guishaozichuan Granules low dose group(0.67 g/kg),positive drug dexamethasone acetate group(0.6 mg/kg),Chinese medicine positive drug Liujunzi Pill +Yupingfeng Powder group(1.80 g/kg + 1.51 g/kg).OVA and AL(OH)3 gel were used to prepare bronchial asthma model rats.On the first day,the rats were injected with(10mg OVA,100 mg AL(OH)3 gel)suspension 1 mL,abdominal 0.5 mL,two groin each 0.25 mL.One week later,the rats were sensitized again.On the 15th day,1%ovalbumin was atomized 30 minutes a day for 10 days.Gastric administration was given 1 hour before nebulization.After 24 hours of the last stimulation,the changes of Ri and Cdyn in rat lung function were measured by atomizing methacholine with increasing concentration in turn.The contents of IgE and cytokines TNF-α,IL-4,IL-5,IL-17 in serum and the contents of LTB4 in alveolar lavage fluid were detected by ELISA.The number of EOS and WBC in alveolar lavage fluid were counted under optical microscope.Lung tissue was stained with HE and pathological changes were observed under light microscope.Results:(1)Airway resistance:Compared with the normal group,the airway resistance of model group rats increased at acetylcholine concentration of 0,3.125,12.5 and 25 mg/mL(P<0.05 or P<0.01).Compared with model group,the airway resistance of Guishaozichuan Granules at low dose and dexamethasone acetate group decreased at acetylcholine concentration of 0 and 3.125 mg/mL(P<0.05 or P<0.01);The airway resistance of Guishaozichuan Granules at medium dose group decreased when the concentration of acylcholine was 3.125 and 12.5 mg/mL(P<0.05);the airway resistance of Guishaozichuan Granules at high dose group decreased when the concentration of acylcholine was 3.125,12.5 and 25 mg/mL(P<0.05 or P<0.01);the airway resistance decreased when the concentration of acetylcholine was 12.5 mg/mL in Yupingfeng granules + Liujunzi pill group(P<0.05).(2)Airway compliance:Compared with the normal group,the airway compliance of rats in the model group decreased at 0 and 12.5 mg/mL of acetylcholine(P<0.05).Compared with the model group,the airway compliance of rats in the Guishaozichuan Granules high dose group decreased at 12.5 mg/mL of acetylcholine(P<0.05);the airway compliance of rats in the dexamethasone acetate group decreased at 3.125 and 12.5 mg/mL of acetylcholine(P<0.05).(3)Immune indices:Compared with the normal group,the levels of serum IgE,IL-4,IL-5,IL-17 and LTB4 in the model group increased(P<0.05),and TNF-a is on the rise.Compared with the model group,the levels of serum IgE and IL-5 in the low-dose Guishaozichuan Granules group decreased(P<0.05),while the levels of serum IgE and IL-5 in the middle-dose Guishaozichuan Granules group decreased(P<0.05).The levels of serum IgE,IL-4,IL-5 and IL-17 in Guishaozichuan Granules high-dose group decreased(P<0.05),while the levels of serum IgE and LTB4 in dexamethasone acetate group decreased(P<0.05),and the levels of serum IgE,IL-4,IL-5,IL-17 and LTB4 in Yupingfeng granules + Liujunzi Pill group decreased(P<0.05).(4)EOS percentage and white blood cell count in alveolar lavage fluid:Compared with normal group,EOS percentage and white blood cell count in alveolar lavage fluid of model group rats increased(P<0.05).Compared with model group,EOS percentage in alveolar lavage fluid of rats in each dose group decreased(P<0.05).The number of white blood cells in alveolar lavage fluid decreased in Guishaozichuan Granules high dose group,dexamethasone acetate group and Yupimgfeng granules + Liujunzi pill group rats(P<0.05).(5)Histopathological observation:In the normal group,the bronchial tube wall was normal,and the mucosal epithelium was intact;no degeneration and necrosis was observed,and the smooth muscle layer was moderately thick,and the cells arranged orderly.In the model group,the bronchial tube wall of the lung tissue was thickened,and the lumen was narrow;the epithelium of the mucosa was degenerated,occasionally necrosis and exfoliation,and the fibrous tissue of the submucosa was proliferated,collagen deposition,and smooth muscle layer was hypertrophic,disordered,interstitial fibrous tissue was proliferated,and a lot of inflammatory cells were infiltrated.Compared with the normal group,pathological score increased in the model group(P<0.01);the lung tissue of rats in Guishaozichuan Granules low,medium and high dose group,dexamethasone acetate group and Yupingfeng granules + Liujunzi pill group slightly thickened bronchial wall,narrowed lumen improved,no degeneration and necrosis of mucosal epithelium,and a small amount of fibers in submucosal layer.Compared with the model group,the pathological score was lower(P<0.01).Conclusion:Guishaozichuan Granules can reduce airway resistance,increase airway compliance,reduce serum levels of IgE,IL-4,IL-5,IL-17 in asthmatic rats,and improve pathological damage of lung tissue.It has certain therapeutic effect on asthmatic rats with airway hyperresponsiveness and airway inflammation.2 Effect of Guishaozichuan Granules on MUC5AC/EGFR Pathway in Bronchial Asthma RatsObjective:To observe the effect of Guishaozichuan Granules on the expression of IL-13,TGF-a,EGFR and MUC5AC in ovalbumin-induced asthmatic rats,and to explore the effect of Guishaozichuan Granules on airway mucus hypersecretion.Methods:OVA and AL(OH)3 gel were used to prepare bronchial asthma model rats.On the first day,the rats were injected with(10 mg OVA,100 mg AL(OH)3 gel)suspension 1 ml,three points(abdominal cavity,two groin),abdominal 0.5 ml,two groin each 0.25 mL.One week later,the rats were sensitized again.On the 15th day,1%ovalbumin was atomized 30 minutes a day for 10 days.Gastric administration was given 1 hour before nebulization.Blood and lung tissue were collected at the end of the experiment.The levels of IL-13 in serum and TGF-α in alveolar lavage fluid were determined by ELISA,the expressions of MUC5AC and EGFR in lung tissue were detected by immunohistochemistry,and the expressions of MUC5AC and EGFR in lung tissue were detected by RT-PCR.Result:Compared with the normal group,the serum IL-13 level in model group increased(P<0.05),the level of TGF-a increased,the levels of MUC5AC and EGFR protein increased(P<0.01),and the levels of MUC5AC and EGFR gene increased(P<0.01).Compared with model group,the expression of MUC5AC and EGFR protein and EGFR gene in the lung tissue of rats in Guishaozichuan Granules group,dexamethasone acetate group,Yupingfeng granules + Liujunzi pill group decreased(P<0.05),and Guishaozichuan Granules decreased(P<0.05).The levels of IL-13 in high dose group,Yupingfeng granules + Liujunzi pill group and TGF-α in Yupingfeng granules + Liujunzi pill group decreased(P<0.05).Conclusion:Guishaozichuan Granules can reduce the level of IL-13 in bronchial asthma rats,down-regulate the expression of MUC5AC and EGFR protein and mRNA,thus regulate the signal pathway of MUC5AC/EGFR in bronchial mucus secretion.These results suggest that Guishaozichuan Granules can improve airway hyperresponsiveness and airway inflammation in bronchial asthma rats,which may be related to its regulation of cytokine levels and MUC5AC/EGFR signaling pathway. |
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