百部生物碱对博来霉素诱导肺纤维化小鼠的保护作用
Protective effects of stemona alkaloids on mice with bleomycin-induced pulmonary fibrosis
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摘要: 对叶百部总生物碱及其主要成分新对叶百部碱对博来霉素诱导肺纤维化小鼠的保护作用进行研究，并采用细胞模型初步探讨其作用机制。实验分为假手术组、模型组、总碱组(60 mg/kg)和新对叶百部碱低、高(10、20 mg/kg)剂量组，泼尼松(6.67 mg/kg)为阳性对照药，以肺组织羟脯氨酸含量、TGF-β1水平、炎性水平、胶原沉积和α-SMA表达等为指标考察其抗肺纤维化效果。结果表明，总碱和新对叶百部碱均能显著改善模型小鼠的肺组织炎症和损伤，降低羟脯氨酸含量和胶原沉积；新对叶百部碱能显著降低模型小鼠肺组织α-SMA表达和TGF-β1水平。初步机制研究表明，新对叶百部碱能抑制TGF-β1诱导的肺成纤维细胞中α-SMA的升高，表明抑制成纤维细胞向肌成纤维细胞转化是其作用机制之一。Abstract: This study aimed to investigate the protective effect of total alkaloids(TA)and one of the active components, neotuberostemonine, of Stemona tuberosa on bleomycin-induced pulmonary fibrosis in mice and to explore the mechanism by fibroblasts model. The bleomycin-induced mice were orally administered with TA(60 mg/kg)and neotuberostemonine(10, 20 mg/kg), with prednisone(6. 67 mg/kg)as a positive control. The anti-fibrotic effects were assessed by hydroxyproline content, TGF-β1 level, inflammatory score, collagen deposition and the expression of α-SMA in the lung tissues. The results revealed that TA and neotuberostemonine could significantly ameliorate the inflammation and injury, and attenuate the hydroxyproline content and collagen deposition. Moreover, neotuberostemonine treatment markedly down-regulated the α-SMA level and TGF-β1 content in bleomycin-injured mice lungs. The in vitro experiments showed that neotuberostemonine inhibited the expression of α-SMA induced by TGF-β1 in a dose-dependent manner, indicating that suppression on differentiation of fibroblasts to myofibroblasts may be one of the mechanisms for neotuberostemonine against pulmonary fibrosis.
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Keywords:
- Stemona tuberosa /
- total alkaloids /
- neotuberostemonine /
- pulmonary fibrosis /
- pulmonary fibroblasts
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