Objective:To explore the presence of inflammatory memory in the lung tissue of mice with cough variant asthma(CVA)and the mechanism of Wuhu decoction in preventing and treating CVA.Methods:Among the 90 SPF-grade femal...Objective:To explore the presence of inflammatory memory in the lung tissue of mice with cough variant asthma(CVA)and the mechanism of Wuhu decoction in preventing and treating CVA.Methods:Among the 90 SPF-grade female BALB/c mice,20 were randomly selected as the blank group,while the remaining 70 were sensitized by intraperitoneal injection of ovalbumin(OVA)combined with aluminum hydroxide and then exposed to OVA by nebulization to establish the CVA mouse model.From the conctrol group and the model group,10 mice were randomly selected to detect airway responsiveness using an animal ventilator.Successfully modeled mice were then randomly divided into 7 groups:a CVA model group,a CVA re-challenge group,low-,medium-,and high-dose Wuhu decoction groups,and a positive control(dexamethasone)group,with 10 mice in each group.After 30 days of rest,except for the conctrol group and the model group,mice in the other groups underwent a second OVA nebulization challenge and received corresponding drug interventions once a day for 10 consecutive days before further analysis.Pathological changes in lung tissue were observed using periodic acid-schiff(PAS)and Masson staining methods.Serum levels of tumor necrosis factor-α(TNF-α),interleukin-4(IL-4),interferon-γ(IFN-γ),and interleukin-10(IL-10)were detected using enzyme-linked immunosorbent assay(ELISA).The expression of T-bet mRNA and GATA-3 mRNA in lung tissue was determined by real-time quantitative polymerase chain reaction(Real-time PCR).Results:The results of airway responsiveness indicated successful establishment of the model.Compared with the control group,the model group exhibited severalkey pathological changes including inflammatory cellinfiltration around the lung tissue,epithelialmetaplasia,airway collagen deposition,increased airway mucus accumulation index and airway collagen deposition index(P<0.05),elevated serum TNF-αand IL-4 expression(P<0.05),decreased IFN-γand IL-10 levels(P<0.05),decreased T-bet mRNA levels(P<0.05),increased GATA-3 mRNA levels(P<0.05),and a reduced T-bet mRNA/GATA-3 mRNA ratio(P<0.05)in lung tissue.When compared to the CVA re-challenge group,the Wuhu decoction groups and the dexamethasone group effectively alleviated pathological changes in lung tissue,reduced the airway mucus accumulation index and airway collagen deposition index(P<0.05),decreased serum TNF-αand IL-4 expression(P<0.05),increased serum IFN-γand IL-10 levels(P<0.05),upregulated T-bet mRNA levels(P<0.05),downregulated GATA-3 mRNA levels(P<0.05),and increased the T-bet mRNA/GATA-3 mRNA ratio(P<0.05)in lung tissue.Conclusion:The lung tissue of mice with cough variant asthma exhibits inflammatory memory,and Wuhu decoction may intervene in this inflammatory memory by restoring the balance between T-bet and GATA-3,thereby correcting the imbalance in Th1/Th2 immunity and exerting a preventive and therapeutic effect on cough variant asthma.展开更多
Objective:To evaluate the therapeutic effect of Glycyrrhetinic Acid on cough variant asthma(CVA)mice and to investigate the possible mechanism in reducing lung inflammation.Methods:48 young female Balb/c mice were div...Objective:To evaluate the therapeutic effect of Glycyrrhetinic Acid on cough variant asthma(CVA)mice and to investigate the possible mechanism in reducing lung inflammation.Methods:48 young female Balb/c mice were divided into Control,CVA,Prednisone Acetate,Glycyrrhetinic Acid high-dose,Glycyrrhetinic Acid middle-dose and Glycyrrhetinic Acid lowdose groups randomly,with 8 mice in each group.The CVA mice model was established by ovalbumin(OVA)sensitization and OVA challenge,the animal asthma behavior was observed after drug administration,and the index of the lung of mice were recorded.The level of OVAsIgE in the bronchoalveolar lavage fluid(BALF)was tested by ELISA.The pathological changes of the lung tissue were observed by Hematoxylin and Eosin(H&E)staining.The protein expressions of T-bet,IFN-γ,Gata3,IL-4 and IL-13 in the lung tissue were determined by Western blot.Results:Compared with the CVA group,the index of lung of mice,the OVA-sIgE level in BALF and expression levels of Th2-related factor in the lung tissue of mice in Prednisone Acetate and Glycyrrhetinic Acid groups were significantly decreased(P<0.05 or P<0.01),the infiltration of inflammatory cells in the lung tissue was reduced,while expressions of Th1-related factor in the lung tissue was significantly increased(P<0.05 or P<0.01).Conclusion:Glycyrrhetinic acid has therapeutic effect on CVA mice,the underlying mechanism of Glycyrrhetinic acid alleviating lung impairment and airway inflammation may be associated with mediating the Th1/Th2 imbalance in the lung tissue.展开更多
目的观察诱导痰黏蛋白水平在嗜酸粒细胞性支气管炎和咳嗽变异性哮喘患者中的差异,分析其与炎症介质和痰细胞学的相关性。方法收集我院在2016年10月~2017年4月门诊诊治的20例EB和20例CVA患者,设为EB组和CVA组,另选取同期健康体检者20例,...目的观察诱导痰黏蛋白水平在嗜酸粒细胞性支气管炎和咳嗽变异性哮喘患者中的差异,分析其与炎症介质和痰细胞学的相关性。方法收集我院在2016年10月~2017年4月门诊诊治的20例EB和20例CVA患者,设为EB组和CVA组,另选取同期健康体检者20例,设为对照组,分析三组对象痰上清黏蛋白MUC5AC、MUC5B、LTC4、PGE2及诱导痰细胞学分类,采用Pearson线性相关分析三者之间的相关性。结果 (1)CVA组MUC5AC水平明显高于EB组和对照组[(25.7±8.6)μg/m L vs(16.4±6.9)μg/m L vs(13.7±5.2)μg/m L],MUC5B水平明显低于EB组和对照组[(1.3±0.7)μg/m L vs(2.7±0.4)μg/m L vs(2.4±0.5)μg/m L,差异有统计学意义(P<0.05);(2)EB组PGE2水平及CVA组LTC4水平明显高于其他两组,差异有统计学意义(P<0.05);(3)Pearson相关性分析得出:MUC5AC水平与Eos、LTC4呈正相关(r=0.771,0.864,P<0.01);MUC5B水平与PGE2呈正相关(r=0.692,P<0.05)。结论 EB和CVA患者诱导痰黏蛋白水平存在明显差异,炎症因子比例失衡与嗜酸粒细胞比例不同可能是引起EB缺乏黏液高分泌的机制。展开更多
文摘Objective:To explore the presence of inflammatory memory in the lung tissue of mice with cough variant asthma(CVA)and the mechanism of Wuhu decoction in preventing and treating CVA.Methods:Among the 90 SPF-grade female BALB/c mice,20 were randomly selected as the blank group,while the remaining 70 were sensitized by intraperitoneal injection of ovalbumin(OVA)combined with aluminum hydroxide and then exposed to OVA by nebulization to establish the CVA mouse model.From the conctrol group and the model group,10 mice were randomly selected to detect airway responsiveness using an animal ventilator.Successfully modeled mice were then randomly divided into 7 groups:a CVA model group,a CVA re-challenge group,low-,medium-,and high-dose Wuhu decoction groups,and a positive control(dexamethasone)group,with 10 mice in each group.After 30 days of rest,except for the conctrol group and the model group,mice in the other groups underwent a second OVA nebulization challenge and received corresponding drug interventions once a day for 10 consecutive days before further analysis.Pathological changes in lung tissue were observed using periodic acid-schiff(PAS)and Masson staining methods.Serum levels of tumor necrosis factor-α(TNF-α),interleukin-4(IL-4),interferon-γ(IFN-γ),and interleukin-10(IL-10)were detected using enzyme-linked immunosorbent assay(ELISA).The expression of T-bet mRNA and GATA-3 mRNA in lung tissue was determined by real-time quantitative polymerase chain reaction(Real-time PCR).Results:The results of airway responsiveness indicated successful establishment of the model.Compared with the control group,the model group exhibited severalkey pathological changes including inflammatory cellinfiltration around the lung tissue,epithelialmetaplasia,airway collagen deposition,increased airway mucus accumulation index and airway collagen deposition index(P<0.05),elevated serum TNF-αand IL-4 expression(P<0.05),decreased IFN-γand IL-10 levels(P<0.05),decreased T-bet mRNA levels(P<0.05),increased GATA-3 mRNA levels(P<0.05),and a reduced T-bet mRNA/GATA-3 mRNA ratio(P<0.05)in lung tissue.When compared to the CVA re-challenge group,the Wuhu decoction groups and the dexamethasone group effectively alleviated pathological changes in lung tissue,reduced the airway mucus accumulation index and airway collagen deposition index(P<0.05),decreased serum TNF-αand IL-4 expression(P<0.05),increased serum IFN-γand IL-10 levels(P<0.05),upregulated T-bet mRNA levels(P<0.05),downregulated GATA-3 mRNA levels(P<0.05),and increased the T-bet mRNA/GATA-3 mRNA ratio(P<0.05)in lung tissue.Conclusion:The lung tissue of mice with cough variant asthma exhibits inflammatory memory,and Wuhu decoction may intervene in this inflammatory memory by restoring the balance between T-bet and GATA-3,thereby correcting the imbalance in Th1/Th2 immunity and exerting a preventive and therapeutic effect on cough variant asthma.
基金National Natural Science Foundation of China (No.81960887)Innovation Project of Guangxi Graduate Education (No.YCXJ2021119)。
文摘Objective:To evaluate the therapeutic effect of Glycyrrhetinic Acid on cough variant asthma(CVA)mice and to investigate the possible mechanism in reducing lung inflammation.Methods:48 young female Balb/c mice were divided into Control,CVA,Prednisone Acetate,Glycyrrhetinic Acid high-dose,Glycyrrhetinic Acid middle-dose and Glycyrrhetinic Acid lowdose groups randomly,with 8 mice in each group.The CVA mice model was established by ovalbumin(OVA)sensitization and OVA challenge,the animal asthma behavior was observed after drug administration,and the index of the lung of mice were recorded.The level of OVAsIgE in the bronchoalveolar lavage fluid(BALF)was tested by ELISA.The pathological changes of the lung tissue were observed by Hematoxylin and Eosin(H&E)staining.The protein expressions of T-bet,IFN-γ,Gata3,IL-4 and IL-13 in the lung tissue were determined by Western blot.Results:Compared with the CVA group,the index of lung of mice,the OVA-sIgE level in BALF and expression levels of Th2-related factor in the lung tissue of mice in Prednisone Acetate and Glycyrrhetinic Acid groups were significantly decreased(P<0.05 or P<0.01),the infiltration of inflammatory cells in the lung tissue was reduced,while expressions of Th1-related factor in the lung tissue was significantly increased(P<0.05 or P<0.01).Conclusion:Glycyrrhetinic acid has therapeutic effect on CVA mice,the underlying mechanism of Glycyrrhetinic acid alleviating lung impairment and airway inflammation may be associated with mediating the Th1/Th2 imbalance in the lung tissue.
文摘目的观察诱导痰黏蛋白水平在嗜酸粒细胞性支气管炎和咳嗽变异性哮喘患者中的差异,分析其与炎症介质和痰细胞学的相关性。方法收集我院在2016年10月~2017年4月门诊诊治的20例EB和20例CVA患者,设为EB组和CVA组,另选取同期健康体检者20例,设为对照组,分析三组对象痰上清黏蛋白MUC5AC、MUC5B、LTC4、PGE2及诱导痰细胞学分类,采用Pearson线性相关分析三者之间的相关性。结果 (1)CVA组MUC5AC水平明显高于EB组和对照组[(25.7±8.6)μg/m L vs(16.4±6.9)μg/m L vs(13.7±5.2)μg/m L],MUC5B水平明显低于EB组和对照组[(1.3±0.7)μg/m L vs(2.7±0.4)μg/m L vs(2.4±0.5)μg/m L,差异有统计学意义(P<0.05);(2)EB组PGE2水平及CVA组LTC4水平明显高于其他两组,差异有统计学意义(P<0.05);(3)Pearson相关性分析得出:MUC5AC水平与Eos、LTC4呈正相关(r=0.771,0.864,P<0.01);MUC5B水平与PGE2呈正相关(r=0.692,P<0.05)。结论 EB和CVA患者诱导痰黏蛋白水平存在明显差异,炎症因子比例失衡与嗜酸粒细胞比例不同可能是引起EB缺乏黏液高分泌的机制。