Neferine，a bisbenzylisoquinline alkaloid attenuates bleomycininduced pulmonary fibrosis in vitro and in vivo
In this study，we evaluated the potential antifibrotic property of neferine，a bisbenzylisoquinline alkaloid extracted from the seed embryo of Nelumbo mucifera Gaertn. Intratracheal bleomycin administration resulted in pulmonary fibrosis 14 and 21 days posttreatment，as evidenced by increased hydroxyproline content in bleomycin group(255.77±97.17μg/lung and 269.74±40.92μg/lung)compared to sham group(170.78±76.46μg/lung and 191.24±60.45μg/lung)，and the hydroxyproline was significantly suppressed(193.07±39.55μg/lung and 201.08±71.74μg/lung)by neferine administration(20 mg/kg，b.i.d). The attenuated-fibrosis condition was also validated by histological observations. Biochemical measurements revealed that bleomycin caused a significant decrease in lung superoxidae dismutase(SOD)activity，which was accompanied with significant increase in malondialdehyde(MDA)levels and myeloperoxiase(MPO)activity on the 7th and 14th day. However，neferine reversed the decrease in SOD activity as well as the increase of MDA and MPO activity. Enzyme-linked immunosorbent assay and radio-immunity assay showed that treatment with neferine alleviated bleomycin induced increase of proinflammatory cytokines such as tumor necrosis factor(TNF)-a，interleukin(IL)-6 and endothelin(ET)1 in plasma or in tissue. Additionally，neferine blocked bleomycin induced increases of NF-?B in nuclear extracts and TGF-? in total protein extracts of murine RAW264.7 macrophages. In conclusion，neferine attenuates bleomycininduced pulmonary fibrosis in vitro and in vivo. The beneficial effect of neferine might be associated with its activities of anti-inflammation，antioxidation，cytokine and NF-?B inhibition.
博莱霉素 肺间质纤维化 甲基莲心碱 巨噬细胞 免疫抑制
Libo Zhao Lin Huang Jialing Wang Yuzhen Li
Peking University People’s Hospital, Beijing, China Department of Pharmacology, Tongji Medical Colle Peking University People’s Hospital, Beijing, China Department of Pharmacology, Tongji Medical College, Wuhan, China
国内会议
石家庄
英文
1-22
2008-10-18（万方平台首次上网日期，不代表论文的发表时间）