The Mechanism of Pingchuanning(平喘宁)Regulating IRE-1α-XBP-1s Signal Axis to Intervene Airway Inflammation in Asthmatic Rats
Objective:To explore the effect and mechanism of Pingchuanning on airway inflammation induced by ovalbumin in asthmatic rats.Method:Totally 105 male SD rats were randomly divided into normal group,model group,dexamethasone group,Guilong Kechuanning(桂龙咳喘宁)group,Pingchuanning high-dose group,Pingchuanning medium-dose group,and Pingchuanning low-dose group,with 15 rats in each group.The asthma model of rats was duplicated with ovalbumin and aluminum hydroxide.After 21 days of modeling,each administration group was given corresponding drugs by gavage,and the normal group and model group were given the same volume of normal saline,once a day for four consecutive weeks.After four weeks of gastric lavage,the rats were dissected and lung tissue and bronchoalveolar lavage fluid(BALF)were removed within two hours after the asthma challenge test.Hematoxylin eosin(HE)staining was used to observe the corresponding pathological changes in lung tissue,such as the thickness of the smooth muscle and the degree of inflammatory cell infiltration.Enzyme linked immunosorbent assay(ELISA)was used to measure the concentrations of IL-5 and IL-17 in BALF.Reverse transcription polymerase chain reaction(RT qPCR)was used to detect the expression levels of IRE-1 α mRNA,XBP-1s mRNA,NF-κB p65 mRNA,Hgsnat mRNA,Pdgfrb mRNA,and Scara3 mRNA.Western blotting was used to detect protein expression level of IRE-1α,XBP-1s and NF-κB p65 in lung tissue.Results:HE staining showed that compared with the model group,the pathological changes in the lung tissue showed varying degrees of relief in each treatment group,including Pingchuanning low-dose group,Pingchuanning medium-dose group,Pingchuanning high-dose group,dexamethasone group and Guilong Kechuanning group.The ELISA results showed that compared with the normal group,the levels of IL-5 and IL-17 in BALF were significantly increased in model group(P<0.01);Compared with the model group,the levels of IL-5 and IL-17 in BALF were significantly reduced in each treatment group(P<0.01),and Pingchuanning showed a dose-dependent effect;Pingchuanning low-dose group and Pingchuanning medium-dose group showed higher levels of IL-5 and IL-17 in BALF than dexamethasone group and Guilong Kechuanning group(P<0.01);Pingchuanning high-dose group showed higher levels of IL-5 in BALF than dexamethasone group and Guilong Kechuanning group(P<0.01),while there was no statistical difference in levels of IL-17 between Pingchuanning high-dose group and the dexamethasone group and Guilong Kechuanning group(P>0.05).The RT-qPCR results showed that compared with the normal group,the relative expression levels of IRE-1 α mRNA,XBP-1s mRNA,and NF-κB p65 mRNA were significantly increased in model group(P<0.01),while the relative expression levels of Hgsnat mRNA,Pdgfrb mRNA,and Scara3 mRNA were significantly reduced(P<0.01);Compared with the model group,the relative expression levels of IRE-1α mRNA,XBP-1s mRNA and NF-κB p65 mRNA were significantly reduced in each treatment group(P<0.01),while the relative expression levels of Hgsnat mRNA,Pdgfrb mRNA,and Scara3 mRNA were significantly increased(P<0.05 or P<0.01);Pingchuanning low-dose group showed higher relative expression levels of IRE-1α mRNA,XBP-1s mRNA and NF-κB p65 mRNA than dexamethasone group and Guilong Kechuanning group(P<0.01),while lower relative expression levels of Hgsnat mRNA,Pdgfrb mRNA,and Scara3 mRNA than dexamethasone group and Guilong Kechuanning group(P<0.01);Pingchuanning medium-dose group showed higher relative expression levels of XBP-1s mRNA and NF-κB p65 mRNA than dexamethasone group and Guilong Kechuanning group(P<0.01),while lower relative expression levels of Hgsnat mRNA,Pdgfrb mRNA,and Scara3 mRNA than dexamethasone group and Guilong Kechuanning group(P<0.05 or P<0.01);There was no statistical difference in IRE-1 α mRNA between Pingchuanning medium-dose group and the dexamethasone group and Guilong Kechuanning group(P>0.05);Pingchuanning high-dose group showed lower relative expression levels of IRE-1α mRNA than dexamethasone group and Guilong Kechuanning group(P<0.01),while higher relative expression levels of Hgsnat mRNA and Pdgfrb mRNA than dexamethasone group(P<0.01);There was no statistical difference in Hgsnat mRNA and Pdgfrb mRNA between Pingchuanning high-dose group and Guilong Kechuanning group(P>0.05);There was no statistical difference in XBP-1s mRNA,NF-κB p65 mRNA and Scara3 mRNA between Pingchuanning high-dose group and the dexamethasone group and Guilong Kechuanning group(P>0.05).Western blotting results showed that compared with the normal group,the relative expression level of IRE-1α,XBP-1s,and NF-κB p65 protein significantly increased in model group(P<0.01);Compared with the model group,the relative expression level of IRE-1α,XBP-1s and NF-κB p65 protein was significantly reduced in each treatment group(P<0.01);Pingchuanning low-dose group showed higher relative expression level of IRE-1α,XBP-1s and NF-κB p65 protein than dexamethasone group and Guilong Kechuanning group(P<0.01);Pingchuanning medium-dose group showed higher relative expression level of XBP-1s and NF-κB p65 protein than dexamethasone group and Guilong Kechuanning group(P<0.05 or P<0.01),and higher relative expression level of IRE-1α protein than Guilong Kechuanning group(P<0.05);There was no statistical difference in relative expression level of IRE-1α between Pingchuanning medium-dose group and dexamethasone group(P>0.05).There was no statistical difference in relative expression of IRE-1α,XBP-1s,and NF-κB p65 between Pingchuanning high-dose group and the dexamethasone group and Guilong Kechuanning group(P>0.05).Conclusion:Pingchuanning can regulate IRE-1α-XBP-1s signal axis to improve airway inflammatory damage in rats with bronchial asthma induced by ovalbumin.
万方数据
维普
