Danggui-Buxue-Tang(DBT) is a famous traditional Chinese formula.We have reported that total glucosides of Dang...
Jian Gao~(a,c,d,1*),Li-jie Feng~(b,1),Yan Huang~c,Ping Li~d,Dujuan Xu~(a,c),Jun Li~c,Qiang Wu~e a,Pharmaceutical preparation section,Third-Grade Pharmaceutical Chemistry Laboratory of State Administration of Traditional Chinese Medicine(TCM-2009-202),the First Affiliated Hospital of Anhui Medical University,Hefei 230022,Anhui,China b,Department of Histology and Embryology,School of Basic Medicine,Anhui Medical University,Hefei 230032,Anhui,China c,School of Pharmacy,Anhui Medical University,Hefei 230032,Anhui,China.d,Key Laboratory of Modern Chinese Medicines(Ministry of Education),China Pharmaceutical University
OBJECTIVE The present study aimed to investigate the relationship between Wnt/β-catenin and Nrf2 signaling pathways,and understanding the mechanisms underlying the process of inflammatory in chronic obstructive pulmonary disease(COPD),which was a serious disease of respiratory system.METHODS We duplicate the emphysema model with porcine pancreatic elastase(PPE)in Nrf2-/-and WT mouse for 21d,and intraperitoneal injection of Li Cl,the activator of Wnt/β-catenin signaling pathway from 14 d to the end.Hematoxylin and eosin(H&E)staining was performed to assess the histopathologic level,and immunohistochemistry(IHC)for Mac-3(the marker of macrophagocyte)and Ly6G(the marker of neutrophil)was used to observe the inflammatory infiltrate,while the levels of Wnt/β-catenin and Nrf2 signaling pathways related proteins heme oxygenase-1(HO-1),NAD(P)H:quinone oxidoreductase 1(NQO1),and the expression of inflammatory cytokine interleukin-6(IL-6)were detected by Western blotting of lung tissues.In vitro,cigarette smoke extract(CSE)-treated normal human bronchial epithelial(NHBE)cells,cell viability was examined by MTT assay,and then we treated recombinant human Wnt3a,si Nrf2 and si Wnt3a to measure the expression of Wnt3a,β-catenin,Nrf2,HO-1,NQO-1,and IL-6.Cellular immunofluorescence staining was employed to identify the nuclear translocation of Nrf2.RESULTS We found that the Li Cl-treated group has markedly decreased the damage of alveolar structure and inflammatory signs than the model group of WT mice rather than Nrf2-/-group.It also seen that Li Cl not only increasedβ-catenin,but it also led to a comparable increase in Nrf2,HO-1,NQO1,and decrease of IL-6 compared with WT model groups but except to Nrf2-/-group in vivo.And it showed that Wnt3atreatment has significantly increased the nuclear translocation of Nrf2 and the expression of HO-1 and NQO1,reduced the IL-6 release,while there has no significance when Nrf2 was blocked in CSE-induced NHBE cells.CONCLUSION Our results demonstrated that Wnt3a/β-catenin significantly
CUI Wen-huiMO Xiao-tingZHOU Wen-chengZHANG Zhi-huiGAO Jian
