Dioscin Exerts Protective Effects Against Crystalline Silica-induced Pulmonary Fibrosis in Mice.
Dioscin Exerts Protective Effects Against Crystalline Silica-induced Pulmonary Fibrosis in Mice.
复制标题
薯蓣皂苷对结晶二氧化硅诱导的小鼠肺纤维化具有保护作用。
作者：
Li C;Lu Y;Du S;Li S;Zhang Y;Liu F;Chen Y;Weng D;Chen J
吸入结晶二氧化硅颗粒导致肺纤维化，最终导致呼吸衰竭和死亡。很少有有效的药物可以延缓这种疾病的进展;因此，矽肺患者通常只提供支持性治疗。薯蓣皂苷是一种甾体皂苷，具有多种生物活性和健康益处，包括其对肝纤维化的保护作用。然而，薯蓣皂苷对矽肺的影响尚不清楚。方法：采用实验性小鼠矽肺模型。在结晶二氧化硅滴注后1天，向动物灌胃不同剂量的薯蓣皂苷，以观察薯蓣皂苷对结晶二氧化硅诱导的肺纤维化的影响。此外，我们使用RAW264.7和NIH-3 T3细胞系来探索薯蓣皂苷对巨噬细胞和成纤维细胞的影响。薯蓣皂苷也是口服治疗，但在结晶二氧化硅滴注后10天观察其对已建立的肺纤维化的影响。结果：薯蓣皂苷治疗通过调节先天性和适应性免疫应答减少促炎症和促纤维化细胞因子分泌。它还减少了纤维细胞的募集，保护上皮细胞免受结晶二氧化硅损伤，抑制转化生长因子β/Smad 3信号传导和成纤维细胞活化。总之，这些作用延缓了结晶二氧化硅诱导的肺纤维化的进展。薯蓣皂苷治疗减轻CS诱导的炎症的机制似乎是通过减少巨噬细胞、B淋巴细胞和T淋巴细胞向肺内的浸润。薯蓣皂苷抑制巨噬细胞和成纤维细胞分泌促炎细胞因子，也可能作为T辅助细胞反应的调节剂，同时减弱凋亡信号调节激酶1-p38/c-Jun N-末端激酶途径的磷酸化。薯蓣皂苷可阻断成纤维细胞Smad 3的磷酸化。口服薯蓣皂苷也能有效延缓矽肺的进展。结论：口服薯蓣皂苷可延缓石英致小鼠肺纤维化，并具有肺保护作用。薯蓣皂苷可能是一种新型且有效的预防结晶二氧化硅诱导的肺纤维化的候选药物。
Inhalation of crystalline silica particles leads to pulmonary fibrosis, eventually resulting in respiratory failure and death. There are few effective drugs that can delay the progression of this disease; thus, patients with silicosis are usually only offered supportive care. Dioscin, a steroidal saponin, exhibits many biological activities and health benefits including its protective effects against hepatic fibrosis. However, the effect of dioscin on silicosis is unknown. Methods: We employed experimental mouse mode of silicosis. Different doses of dioscin were gavaged to the animals 1 day after crystalline silica instillation to see the effect of dioscin on crystalline silica induced pulmonary fibrosis. Also, we used RAW264.7 and NIH-3T3 cell lines to explore dioscin effects on macrophages and fibroblasts. Dioscin was also oral treatment but 10 days after crystalline silica instillation to see its effect on established pulmonary fibrosis. Results: Dioscin treatment reduced pro-inflammation and pro-fibrotic cytokine secretion by modulating innate and adaptive immune responses. It also reduced the recruitment of fibrocytes, protected epithelial cells from crystalline silica injury, inhibited transforming growth factor beta/Smad3 signaling and fibroblast activation. Together, these effects delayed the progression of crystalline silica-induced pulmonary fibrosis. The mechanism by which dioscin treatment alleviated CS-induced inflammation appeared to be via the reduction of macrophage, B lymphocyte, and T lymphocte infiltration into lung. Dioscin inhibits macrophages and fibroblasts from secreting pro-inflammatory cytokines and may also function as a modulator of T helper cells responses, concurrent with attenuated phosphorylation of the apoptosis signal-regulating kinase 1-p38/c-Jun N-terminal kinase pathway. Also, dioscin could block the phosphorylation of Smad3 in fibroblast. Oral treatment of dioscin could also effectively postpone the progression of established silicosis. Conclusion: Oral treatment dioscin delays crystalline silica-induced pulmonary fibrosis and exerts pulmonary protective effects in mice. Dioscin may be a novel and potent candidate for protection against crystalline silica-induced pulmonary fibrosis.
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影响因子：
3.7
作者：
Liu F;Liu J;Weng D;Chen Y;Song L;He Q;Chen J
通讯作者：
Chen J
影响因子：
3.3
作者：
Kage H;Borok Z
通讯作者：
Borok Z
影响因子：
6
作者：
Lakos, G;Takagawa, S;Varga, J
通讯作者：
Varga, J
阻断卵泡抑素样 1 可减轻博莱霉素诱导的小鼠肺纤维化
DOI：
10.1084/jem.20121878
发表时间：
2015-02-09
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Dong Y;Geng Y;Li L;Li X;Yan X;Fang Y;Li X;Dong S;Liu X;Li X;Yang X;Zheng X;Xie T;Liang J;Dai H;Liu X;Yin Z;Noble PW;Jiang D;Ning W
通讯作者：
Ning W
影响因子：
4.7
作者：
Han, Ruhui;Ji, Xiaoming;Ni, Chunhui
通讯作者：
Ni, Chunhui