Hirsutella sinensis mycelium attenuates bleomycin-induced pulmonary inflammation and fibrosis in vivo.
Hirsutella sinensis mycelium attenuates bleomycin-induced pulmonary inflammation and fibrosis in vivo.
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DOI：
10.1038/srep15282
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发表时间：
2015-10-26
影响因子：
4.6
通讯作者：
Chong KY
中科院分区：
文献类型：
--
作者：
Huang TT;Lai HC;Ko YF;Ojcius DM;Lan YW;Martel J;Young JD;Chong KY
中国被毛孢菌丝体是冬虫夏草的无性型，是一种具有多种药理活性的传统中药。我们以前报道过，这种真菌通过抑制人巨噬细胞中的典型和非典型炎性小体来抑制白细胞介素-1 β和IL-18的分泌。然而，HSM是否可用于预防肺纤维化以及这种活性的机制仍不清楚。结果表明，HSM预处理可抑制TGF-β1诱导的肺成纤维细胞纤连蛋白和α-SMA的表达。HSM还恢复TGF-β1处理的肺成纤维细胞中超氧化物歧化酶的表达，并抑制肺上皮细胞中活性氧的产生。此外，HSM预处理显著减少博莱霉素诱导的小鼠肺损伤和纤维化。因此，HSM减少支气管肺泡灌洗液中的炎性细胞积聚和肺组织中的促炎细胞因子水平。HSM提取物还显著降低肺组织中的TGF-β1，并且这种作用伴随着胶原3α1和α-SMA水平的降低。此外，HSM降低肺组织中NLRP 3炎性体和P2 X7 R的表达，而其增强超氧化物歧化酶的表达。这些结果表明，HSM可用于治疗肺部炎症和纤维化。
Hirsutella sinensis mycelium (HSM), the anamorph of Cordyceps sinensis, is a traditional Chinese medicine that has been shown to possess various pharmacological properties. We previously reported that this fungus suppresses interleukin-1β and IL-18 secretion by inhibiting both canonical and non-canonical inflammasomes in human macrophages. However, whether HSM may be used to prevent lung fibrosis and the mechanism underlying this activity remain unclear. Our results show that pretreatment with HSM inhibits TGF-β1–induced expression of fibronectin and α-SMA in lung fibroblasts. HSM also restores superoxide dismutase expression in TGF-β1–treated lung fibroblasts and inhibits reactive oxygen species production in lung epithelial cells. Furthermore, HSM pretreatment markedly reduces bleomycin–induced lung injury and fibrosis in mice. Accordingly, HSM reduces inflammatory cell accumulation in bronchoalveolar lavage fluid and proinflammatory cytokines levels in lung tissues. The HSM extract also significantly reduces TGF-β1 in lung tissues, and this effect is accompanied by decreased collagen 3α1 and α-SMA levels. Moreover, HSM reduces expression of the NLRP3 inflammasome and P2X7R in lung tissues, whereas it enhances expression of superoxide dismutase. These findings suggest that HSM may be used for the treatment of pulmonary inflammation and fibrosis.