Genistein-3 '-sodium sulphonate protects against lipopolysaccharide-induced lung vascular endothelial cell apoptosis and acute lung injury via BCL-2 signalling
Genistein-3 '-sodium sulphonate protects against lipopolysaccharide-induced lung vascular endothelial cell apoptosis and acute lung injury via BCL-2 signalling
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DOI：
10.1111/jcmm.14815
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发表时间：
2020
影响因子：
5.3
通讯作者：
Huan Jingning
中科院分区：
文献类型：
--
作者：
Yi Lei;Chang Mengling;Zhao Quanming;Zhou Zengding;Huang Xiaoqin;Guo Feng;Huan Jingning
在脓毒症条件下，脂多糖(LPS)诱导肺血管内皮细胞(ECs)凋亡，触发并加重急性肺损伤(ALI)，目前尚无有效的治疗方法。染料木素-3‘-磺酸钠(GSS)是天然大豆异黄酮的衍生物，通过其抗细胞凋亡作用而具有神经保护作用。然而，GSS是否对脓毒症诱导的肺血管内皮细胞凋亡和ALI具有保护作用尚未确定。在本研究中，我们发现GSS在体外能有效地下调脂多糖诱导的MyD88/NF-κB/bcl2信号通路激活和随后的EC凋亡。此外，GSS不仅逆转了脓毒症诱导的小鼠肺组织bcl2表达的变化，还在体内阻断了脓毒症相关的肺血管屏障破坏和ALI。综上所述，GSS可能通过调节肺内皮细胞MyD88/NF-κB/bc1-2信号通路而成为治疗脓毒症所致ALI的候选药物。
Under septic conditions, Lipopolysaccharide (LPS)‐induced apoptosis of lung vascular endothelial cells (ECs) triggers and aggravates acute lung injury (ALI), which so far has no effective therapeutic options. Genistein‐3′‐sodium sulphonate (GSS) is a derivative of native soy isoflavone, which has neuro‐protective effects through its anti‐apoptotic property. However, whether GSS protects against sepsis‐induced lung vascular endothelial cell apoptosis and ALI has not been determined. In this study, we found that LPS‐induced Myd88/NF‐κB/BCL‐2 signalling pathway activation and subsequent EC apoptosis were effectively down‐regulated by GSS in vitro. Furthermore, GSS not only reversed the sepsis‐induced BCL‐2 changes in expression in mouse lungs but also blocked sepsis‐associated lung vascular barrier disruption and ALI in vivo. Taken together, our results demonstrated that GSS might be a promising candidate for sepsis‐induced ALI via its regulating effects on Myd88/NF‐κB/BCL‐2 signalling in lung ECs.