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阿沙托酮通过降低 NF-[公式:见文本]B、MAPK 和炎症细胞因子的表达来预防急性肺损伤。

Asatone Prevents Acute Lung Injury by Reducing Expressions of NF-[Formula: see text]B, MAPK and Inflammatory Cytokines.

机构信息

* School of Post-Baccalaureate Chinese Medicine, Tzu Chi University, Hualien 970, Taiwan.

† School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung 404, Taiwan.

出版信息

Am J Chin Med. 2018;46(3):651-671. doi: 10.1142/S0192415X18500349. Epub 2018 Mar 29.

DOI:10.1142/S0192415X18500349
PMID:29595073
Abstract

Asatone is an active component extracted from the Chinese herb Radix et Rhizoma Asari. Our preliminary studies have indicated that asatone has an anti-inflammatory effect on RAW 264.7 culture cells challenged with lipopolysaccharide (LPS). Acute lung injury (ALI) has high morbidity and mortality rates due to the onset of serious lung inflammation and edema. Whether asatone prevents ALI LPS-induced requires further investigation. In vitro studies revealed that asatone at concentrations of 2.5-20[Formula: see text][Formula: see text]g/mL drastically prevented cytotoxicity and concentration-dependently reduced NO production in the LPS-challenged macrophages. In an in vivo study, the intratracheal administration of LPS increased the lung wet/dry ratio, myeloperoxidase activity, total cell counts, white blood cell counts, NO, iNOS, COX, TNF-[Formula: see text], IL-1[Formula: see text], and IL-6 in the bronchoalveolar lavage fluid as well as mitogen-activated protein kinases in the lung tissues. Pretreatment with asatone could reverse all of these effects. Asatone markedly reduced the levels of TNF-[Formula: see text] and IL-6 in the lung and liver, but not in the kidney of mice. By contrast, LPS reduced anti-oxidative enzymes and inhibited NF-[Formula: see text]B activations, whereas asatone increased anti-oxidative enzymes in the bronchoalveolar lavage fluid and NF-[Formula: see text]B activations in the lung tissues. Conclusively, asatone can prevent ALI through various anti-inflammatory modalities, including the major anti-inflammatory pathways of NF-[Formula: see text]B and mitogen-activated protein kinases. These findings suggest that asatone can be applied in the treatment of ALI.

摘要

细辛脑是从中药北细辛中提取的一种活性成分。我们的初步研究表明,细辛脑对脂多糖(LPS)刺激的 RAW264.7 细胞具有抗炎作用。急性肺损伤(ALI)由于严重的肺炎症和水肿而具有高发病率和死亡率。细辛脑是否能预防脂多糖诱导的 ALI 还需要进一步研究。体外研究表明,细辛脑在 2.5-20μg/ml 的浓度下可显著防止 LPS 刺激的巨噬细胞的细胞毒性,并呈浓度依赖性降低 NO 的产生。在体内研究中,气管内给予 LPS 增加了肺湿/干比、髓过氧化物酶活性、总细胞计数、白细胞计数、NO、iNOS、COX、TNF-α、IL-1β和 IL-6 在支气管肺泡灌洗液中的水平,以及肺组织中的丝裂原激活蛋白激酶。细辛脑预处理可逆转所有这些作用。细辛脑可显著降低肺和肝组织中 TNF-α和 IL-6 的水平,但对肾脏无影响。相反,LPS 降低了抗氧化酶的活性,并抑制了 NF-κB 的激活,而细辛脑增加了支气管肺泡灌洗液中的抗氧化酶和 NF-κB 在肺组织中的激活。综上所述,细辛脑可以通过多种抗炎途径预防 ALI,包括 NF-κB 和丝裂原激活蛋白激酶的主要抗炎途径。这些发现表明,细辛脑可用于治疗 ALI。

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