Resveratrol Protects against Sepsis-Associated Encephalopathy and Inhibits the NLRP3/IL-1β Axis in Microglia.
Resveratrol Protects against Sepsis-Associated Encephalopathy and Inhibits the NLRP3/IL-1β Axis in Microglia.
复制标题
白藜芦醇可预防脓毒症相关脑病并抑制小胶质细胞中的 NLRP3/IL-1β 轴
DOI：
10.1155/2016/1045657
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发表时间：
2016
影响因子：
4.6
通讯作者：
Deng XM
中科院分区：
文献类型：
--
作者：
Sui DM;Xie Q;Yi WJ;Gupta S;Yu XY;Li JB;Wang J;Wang JF;Deng XM
脓毒症相关脑病（SAE）的特征是脓毒症相关的脑功能障碍。在这项研究中，我们试图研究白藜芦醇在SAE小鼠中的作用，以及其在SAE发病机制中至关重要的NLRP 3炎性小体和IL-1β中的作用。通过盲肠结扎穿孔（CLP）诱导小鼠SAE，手术后给予两个剂量的白藜芦醇。Morris水迷宫实验评价大鼠空间学习记忆功能。采用TUNEL法检测海马细胞凋亡。通过测量小胶质细胞活化、NLRP 3和IL-1β的水平来定量海马中的炎症。白藜芦醇处理的CLP小鼠在水迷宫训练中表现出更好的空间记忆。TUNEL检测表明，白藜芦醇处理的小鼠的细胞凋亡率显着减弱，同时减少海马区的iba-1阳性小胶质细胞的数量。白藜芦醇剂量依赖性地抑制NLRP 3表达和IL-1β裂解。体外实验结果表明，在BV 2细胞系中，白藜芦醇可阻止ATP诱导的NLRP 3激活和IL-1β裂解，这可被沉默调节蛋白1抑制剂烟酰胺逆转。结论：白藜芦醇能改善SAE小鼠的空间记忆，抑制小胶质细胞NLRP 3/IL-1β轴的表达。
Sepsis-associated encephalopathy (SAE) is characterized as brain dysfunction associated with sepsis. In this study we sought to investigate the effects of resveratrol in mice with SAE, as well as its effects in NLRP3 inflammasome and IL-1β, which were critical in the pathogenesis of SAE. SAE was induced in mice via cecal ligation and puncture (CLP), and resveratrol was administered at two doses after surgery. Spatial learning memory functions were evaluated by Morris water maze testing. Apoptosis in the hippocampus was quantified using TUNEL assay. Inflammation in the hippocampus was quantified by measuring the levels of microglial activation, NLRP3, and IL-1β. CLP mice treated with resveratrol demonstrated a better spatial memory during water maze training. The TUNEL assay demonstrated significantly attenuated rates of apoptosis, in resveratrol treated mice, while decreasing the number of iba-1 positive microglia in the hippocampus region. NLRP3 expression and IL-1β cleavage were well inhibited by resveratrol dose-dependently. The in vitro results showed that in the BV2 cell lines resveratrol prevents ATP induced NLRP3 activation and IL-1β cleavage, which were reversed by the sirtuin 1 inhibitor, nicotinamide. In conclusion, resveratrol improves the spatial memory in mice with SAE and inhibits the NLRP3/IL-1β axis in the microglia.