Tanshinone IIA protects against subclinical lipopolysaccharide induced cardiac fibrosis in mice through inhibition of NADPH oxidase
Tanshinone IIA protects against subclinical lipopolysaccharide induced cardiac fibrosis in mice through inhibition of NADPH oxidase
复制标题
丹参酮 IIA 通过抑制 NADPH 氧化酶预防亚临床脂多糖诱导的小鼠心脏纤维化
DOI：
10.1016/j.intimp.2018.04.036
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发表时间：
2018-07-01
影响因子：
5.6
通讯作者：
Zhu, Minghui
中科院分区：
文献类型：
--
作者：
Huang, Libing;Zhu, Juan;Zhu, Minghui
心肌纤维化在心力衰竭的发展中起着核心作用。研究表明，反复暴露于亚临床脂多糖（LPS）会增加小鼠的死亡率并诱发心脏纤维化，而这不是由常见的肾素-血管紧张素系统介导的。脂多糖使离体成年小鼠心肌成纤维细胞NADPH氧化酶2 （NOX2）升高，NOX2可能介导脂多糖诱导的心肌纤维化。因此，本研究旨在描述NOX2在lps诱导的纤维化模型中的作用，并探讨丹参酮IIA （TIIA）对心脏纤维化发生的预防作用。通过与NADPH氧化酶抑制剂罗布麻苷的比较，确定TIIA的保护机制与NOX2的抑制有关。结果显示，罗布麻素和TIIA对心肌纤维化及纤维化相关基因和介质的发展有显著的抑制作用。此外，TIIA和apocynin降低了NADPH氧化酶亚基（NOX2和P67(Phox)）的表达和ROS水平。罗布麻素的抗纤维化作用提示抑制NOX2可能是一种潜在的预防策略，可以减轻脂多糖诱导的心脏纤维化的进展。我们的研究结果表明，TIIA可能是一种有效的药物，部分通过抑制NADPH氧化酶2来对抗亚临床lps诱导的小鼠心脏纤维化。
Myocardial fibrosis plays a central role in the development of heart failure. It has been shown that recurrent exposure to subclinical lipopolysaccharide (LPS) increases mortality and induces cardiac fibrosis in mice, which is not mediated by the common renin-angiotensin system. LPS increased NADPH oxidase2 (NOX2) in isolated adult mouse cardiac fibroblasts and NOX2 may mediate LPS-induced cardiac fibrosis. Therefore, the current study was designed to delineate the role of NOX2 in LPS-induced fibrosis model and to investigate the preventive role of Tanshinone IIA (TIIA) on the development of cardiac fibrosis. The protective mechanism of TIIA was determined to be associated with the inhibition of NOX2, by comparing its effects with the NADPH oxidase inhibitor, apocynin. The results revealed remarkable effects of apocynin and TIIA on attenuating the development of myocardial fibrosis and fibrosis-related genes and mediators. Furthermore, TIIA and apocynin decreased the expression of NADPH oxidase subunits (NOX2 and P67(Phox)) expression and the ROS levels. The anti-fibrotic effect of apocynin suggested that NOX2 inhibition may be a potential preventive strategy for attenuating the progression of LPS-induced cardiac fibrosis. Our results demonstrate that TIIA may be a potent agent against subclinical LPS-induced cardiac fibrosis in mice partially via inhibition of NADPH oxidase 2.