Liu Yujuan, Huang Guojin, Mo Biwen, Wang Changming
Division of Respiratory Diseases, Affiliated Hospital of Guilin Medical University, Guilin, Guangxi 541001, P.R. China.
Exp Ther Med. 2017 Jul;14(1):561-566. doi: 10.3892/etm.2017.4573. Epub 2017 Jun 8.
The present study aimed to determine the underlying molecular mechanism of the antifibrotic effect of artesunate in pulmonary fibrosis (PF). Primary lung fibroblasts were isolated from the lung tissues of rats, and treated with artesunate (8 µg/ml) and transforming growth factor (TGF)-β1 (5 ng/ml). For experiments, the rats were administered bleomycin intratracheally, followed by daily intraperitoneal artesunate injections for 27 days. Western blotting, and immunohistochemical and immunofluorescent staining were used to assess the expression of key components of the Notch signaling pathway, including α-smooth muscle actin (α-SMA) and type IV collagen. Artesunate (8 µg/ml) was identified to inhibit TGF-β1-induced α-SMA and collagen protein expression, and repress the Notch signaling pathway, in primary lung fibroblasts. Downregulation of α-SMA and collagen by artesunate was associated with inhibition of the Notch signaling pathway. The daily intraperitoneal injection of artesunate (1 mg/kg) in rats was determined to inhibit bleomycin-induced overexpression of α-SMA and type IV collagen proteins, and inhibit the Notch signaling pathway, in lung tissues. In conclusion, the results of the current study indicate that artesunate inhibits the TGF-β1-induced differentiation of rat primary lung fibroblasts into myofibroblasts and ameliorates bleomycin-induced PF. In addition, the results of the present study suggest that the underlying molecular mechanism for these effects of artesunate is repression of the Notch signaling pathway.
本研究旨在确定青蒿琥酯在肺纤维化（PF）中抗纤维化作用的潜在分子机制。从大鼠肺组织中分离出原代肺成纤维细胞，并用青蒿琥酯（8μg/ml）和转化生长因子（TGF）-β1（5ng/ml）进行处理。在实验中，对大鼠进行气管内注射博来霉素，随后每天腹腔注射青蒿琥酯，持续27天。采用蛋白质免疫印迹法以及免疫组织化学和免疫荧光染色法评估Notch信号通路关键成分的表达，包括α-平滑肌肌动蛋白（α-SMA）和IV型胶原。已确定青蒿琥酯（8μg/ml）可抑制TGF-β1诱导的原代肺成纤维细胞中α-SMA和胶原蛋白的表达，并抑制Notch信号通路。青蒿琥酯对α-SMA和胶原蛋白的下调与Notch信号通路的抑制有关。已确定每天对大鼠腹腔注射青蒿琥酯（1mg/kg）可抑制博来霉素诱导的肺组织中α-SMA和IV型胶原蛋白的过表达，并抑制Notch信号通路。总之，本研究结果表明，青蒿琥酯可抑制TGF-β1诱导的大鼠原代肺成纤维细胞向肌成纤维细胞的分化，并改善博来霉素诱导的PF。此外，本研究结果表明，青蒿琥酯产生这些作用的潜在分子机制是对Notch信号通路的抑制。
