基于cAMP/PKA/CREB信号通路探讨固本止咳方治疗慢性阻塞性肺疾病稳定期小鼠的作用机制
Mechanism of Guben ZhiKe Formula on COPD in stable mice based on cAMP/PKA/CREB signal pathway
洪政 1方晗语 1刘明非 1邹浩 1刘颖 2张洪春2
作者信息
- 1. 北京中医药大学,北京 100029
- 2. 中日友好医院中医肺部一部,北京 100029
- 折叠
摘要
目的 基于环磷酸腺苷(cAMP)/蛋白激酶A(PKA)/cAMP反应元件结合蛋白(CREB)信号通路探讨固本止咳方(GBZK)治疗慢性阻塞性肺疾病(COPD)稳定期小鼠的作用机制.方法 60只BALB/c小鼠随机分为对照组、模型组、GBZK组、地塞米松组,除对照组外,其余组均使用烟草烟雾暴露联合脂多糖复制COPD稳定期小鼠模型.造模成功后,GBZK组予GBZK 0.2 mL/d灌胃,地塞米松组予1.0 mg/kg地塞米松注射液腹腔注射,2次/d,所有小鼠均给药28 d.观察各组小鼠一般情况,酶联免疫吸附测定法(ELISA)检测小鼠肺组织匀浆cAMP水平,利用Western blot检测小鼠肺组织匀浆中cAMP、p-PKA、CREB、p-CREB蛋白表达情况.结果 与模型组比较,GBZK组小鼠的喘息气促有所改善,肺组织匀浆中cAMP含量及cAMP、p-PKA、CREB、p-CREB蛋白表达均提高(P<0.05).结论 固本止咳方可能通过激活cAMP/PKA/CREB信号通路,进而发挥对COPD稳定期小鼠的保护作用.
Abstract
Objective To observe the effect of Guben Zhike Formula(GBZK)on mice in stable stage of chronic obstructive pulmonary disease(COPD),and to explore the mechanism of action of GBZK on mice in stable stage of COPD based on cAMP/PKA/CREB signaling pathway.Methods 60 BALB/c mice were randomly and equally divided into 4 groups,that is control group,model group,GBZK group and dexamethasone group,except for the control group,the rest of the groups were replicated with cigarettesmoke exposure combined with lipopolysaccharide in COPD stable stage mouse model.After the mice were established with COPD model,corresponding drug interventions were given and GBZK was gavaged continuously of 0.2 mL/(d·each),the dexamethasone group was given intraperitoneal injection of 1.0 mg/kg dexamethasone injection twice a day,all for 28 days.The general conditions of mice in each group were observed;cAMP levels in mouse lung tissue homogenates were detected by enzyme-linked immunosorbent assay(ELISA);protein expression of cAMP,p-PKA,CREB,and p-CREB were detected in mouse lung tissue homogenates using Western blotting.Results Compared with the model group,the wheezing shortness of breath was improved and the cAMP content in lung tissue homogenates increased in the GBZK Group(P<0.05),and the protein expression of cAMP,p-PKA,CREB,and p-CREB(P<0.05)were all increased(P<0.05).Conclusion GBZK may play a protective role in stable COPD mice by activating the cAMP/PKA/CREB signaling pathway.
关键词
固本止咳方/慢性阻塞性肺疾病/cAMP/PKA/CREB/小鼠Key words
Guben Zhike Formula/COPD/cAMP/PKA/CREB/mice引用本文复制引用
基金项目
国家自然科学基金(82074367)
国家重点研发计划(2019YFC1712003)
出版年
2024
国家科技期刊平台
NSTL
万方数据