| Objective: To observe the therapeutic effect of Guben Pingchuan prescription on stable phase of chronic obstructive pulmonary disease(COPD)model rats,and based on Notch/Hes/MUC5 AC pathway to explore the mechanism of Guben Pingchuan Recipe from the perspective of airway mucus hypersecretion.Methods: The experiment selected 64 SD rats,which were divided into 6 groups according to the random table: blank control group,model group,dexamethasone group,Guben Pingchuan high,medium and low dose group.control and model group separately had 12 rats,The remaining groups have 10 rats.Except for the blank control group,COPD rat model was established by cigarette smoke exposure combined with intratracheal instillation of LPS and PPE in each group.Meanwhile,the control group received an intratracheal injection of an equal volume of normal saline and was not passively smoked,The modeling period was 28 days.After the model was completed,the blank control group and the model group were given normal saline,Other group were given the corresponding drug for 2 weeks.After treatment,the general condition of rats in each group was observed;HE staining was used to observe the pathological changes of the lung;The content of TNF-α、IL-8 and MUC5 AC in serum were detected by ELISA;The levels of Notch3,Hes1 and MUC5 AC in rat lung tissues were determined by RT-qPCR and the protein expressions of Notch3,Hes1 and MUC5 AC were determined by WB.Results: 1.General conditions: compared with the blank control group,the rats in the other groups showed different degrees of cough,sneezing,asthma and other symptoms,listlessness,mouth and nose secretions,yellow and dull fur,slow activity,dislike movement,significantly less food intake,obvious emaciation,and slow weight gain.The general condition of the model group changed the most obviously,followed by the low dose of Guben Pingchuan prescription group,the high dose of Guben Pingchuan prescription group changed the least,the middle dose of Guben Pingchuan prescription group and the dexamethasone group had similar changes,and their changes were more obvious than the high dose of Guben Pingchuan prescription.2.HE staining: compared with the blank control group,the other groups had different degrees of pathological changes: the bronchial wall was significantly thickened,a large number of inflammatory cells infiltrated,the alveolar septum was significantly enlarged,and the septum between some alveoli was thinned,broken,and even the formation of pulmonary bullae.The changes in the model group were the most obvious,Low dose Guben Pingchuan prescription group followed,The high-dose Guben Pingchuan prescription group showed the least significant changes,The changes of Guben Pingchuan prescription middle-dose group and dexamethasone group were similar,and their changes were more obvious than the high dose of Guben Pingchuan prescription.3.ELISA: Compared with the blank control group,the serum levels of TNF-α,IL-8 and MUC5 AC in the other groups were increased to varying degrees,and the serum levels of TNF-α,IL-8 and MUC5 AC in the model group were the highest,followed by the low-dose Guben Pingchuan prescription group.The serum levels of dexamethasone group were lower than the low-dose Guben Pingchuan prescription group,but higher than the high-dose and the middle-dose Guben Pingchuan prescription groups,the high-dose Guben Pingchuan prescription group were the lowest(all P < 0.05).4.RT-qPCR: Compared with the blank control group,the expression levels of Notch3,Hes1 and MUC5 AC m RNA in the lung tissues of the other groups were increased to varying degrees,and the expression in the model group were the highest,followed by the low dose Guben Pingchuan prescription group.The expression in the dexamethasone group were lower than the low-dose Guben Pingchuan prescription group,but higher than the high-dose and the middle-dose Guben Pingchuan prescription groups.the high-dose Guben Pingchuan prescription group were the lowest(all P < 0.05).5.WB: Compared with the blank control group,the protein expressions of Notch3,Hes1 and MUC5 AC in the lung tissues of the other groups increased to varying degrees.The protein expression in the model group were the highest,followed by the low-dose Guben Pingchuan prescription group,the expression of protein in the high-dose Guben Pingchuan prescription group were the lowest.the middle dose of Guben Pingchuan prescription group and the dexamethasone group were similar,but they higher than the high-dose group(all P < 0.05).Conclusion: 1.Through the experiment to observe the general condition of each group of rats and the interpretation of HE staining results,it has been successfully verified that cigarette smoke exposure combined with intratracheal instillation of LPS and PPE can successfully establish COPD rat model.2.Guben Pingchuan prescription can improve the general condition of COPD model rats,reduce the pathological damage of lung tissue,and reduce the inflammatory response in COPD model rats,of which the improvement is more obvious in the high-dose group of Guben Pingchuan prescription.3.Based on the results of this experimental study,it can be inferred that Guben Pingchuan prescription can inhibit the high secretion of airway mucus,and the mechanism may be related to the inhibition of Notch/Hes/MUC5 AC signaling pathway activation. |
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