Curcumin reduces LPS-induced septic acute kidney injury through suppression of lncRNA PVT1 in mice
Curcumin reduces LPS-induced septic acute kidney injury through suppression of lncRNA PVT1 in mice
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DOI：
10.1016/j.lfs.2020.117340
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发表时间：
2020-08-01
期刊：
影响因子：
6.1
通讯作者：
Niu, Fangfang
中科院分区：
文献类型：
--
作者：
Huang, Wei;Li, Xueting;Niu, Fangfang
目的研究姜黄素对内毒素诱导的感染性急性肾损伤的保护作用，并探讨其分子机制。方法建立脓毒症急性肾损伤(AKI)小鼠模型。结果姜黄素能显著降低脂多糖诱导的急性肾损伤小鼠血清Scr、BUN、Cyc水平，减轻肾脏损伤。内毒素诱导的急性肾损伤小鼠肾组织中PVT1、ED-1、肿瘤坏死因子-α、IL-1β、IL-6、p-IkBα/IkBα、p-p65/p65、p-jnk/jnk、p-c-jun/c-jun表达增加，而姜黄素治疗后这种作用明显减弱。姜黄素可提高脂多糖致炎NRK细胞的存活率。此外，过度表达PVT1的NRK细胞的存活率低于从接受内毒素治疗后接受姜黄素治疗的小鼠获得的WT NRK细胞。姜黄素可降低脂多糖诱导的NRK细胞bax、裂解caspase3/caspase3、p-ikbα/ikbα、p-p65/p65、p-jnk/jnk、p-c-jun/c-jun蛋白表达，增加bcl2蛋白表达。结论姜黄素可降低内毒素诱导的脓毒症小鼠急性肾组织中PVT1的表达，减轻内毒素诱导的小鼠急性肾损伤。这可能与姜黄素通过抑制lncRNAPVT1而抑制JNK/NF-κB通路有关。
ObjectiveTo investigate the protective effects of curcumin on LPS-induced septic acute kidney injury and to explore its underlying molecular mechanisms.MethodsA mouse model of septic acute kidney injury (AKI) was given an intraperitoneal injection of lipopolysaccharide (LPS), followed by administration of variable levels of curcumin (intragastric). And NRK cells were used as the kidney cell model for allin vitrostudies.ResultsCurcumin significantly decreased the levels of serum Scr, BUN, and Cyc c and reduced kidney injury in LPS-induced AKI mice. Kidney tissues of LPS-induced AKI mice showed an increase in PVT1, ED-1, TNF-α, IL-1β, IL-6, p-IkBα/IkBα, p-p65/p65, p-JNK/JNK, and p-c-JUN/c-JUN expression levels; however, treatment with curcumin significantly reduced this effect. Curcumin increased the survival rate NRK cells exposed to LPS-induced inflammationin vitro. Moreover, NRK cells that overexpressed PVT1 had lower survival rates than WT NRK cells obtained from mice that received curcumin treatment after treating with LPS. Additionally, curcumin reduced the LPS-induced increase in Bax, cleaved-caspase3/caspase 3, p-IkBα/IkBα, p-p65/p65, p-JNK/JNK, and p-c-JUN/c-JUN protein expression, and increased Bcl2 protein expression in NRK cells. However, the extent of these changes was low in NRK cells that overexpressed PVT1.ConclusionCurcumin decreased PVT1 expression in LPS-induced septic acute kidney tissues and reduced LPS-induced septic acute kidney injury in mice. This might be related to the inhibition of the JNK/NF-κB pathway by curcumin through suppression of lncRNA PVT1.