Resveratrol Attenuates Early Brain Injury after Experimental Subarachnoid Hemorrhage via Inhibition of NLRP3 Inflammasome Activation.
Resveratrol Attenuates Early Brain Injury after Experimental Subarachnoid Hemorrhage via Inhibition of NLRP3 Inflammasome Activation.
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白藜芦醇通过抑制 NLRP3 炎性体激活减轻实验性蛛网膜下腔出血后的早期脑损伤。
DOI：
10.3389/fnins.2017.00611
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发表时间：
2017
影响因子：
4.3
通讯作者：
Hang C
中科院分区：
文献类型：
--
作者：
Zhang X;Wu Q;Zhang Q;Lu Y;Liu J;Li W;Lv S;Zhou M;Zhang X;Hang C
研究表明白藜芦醇（resveratrol，RSV）对蛛网膜下腔出血（subarachnoid hemorrhage，SAH）后的早期脑损伤（early brain injury，EBI）有一定的治疗作用。然而，RSV的有益作用和潜在机制尚未明确确定。核苷酸结合寡聚化结构域样受体家族含pyrin结构域3（NLRP 3）炎性体激活在EBI发病机制中发挥着至关重要的作用。本研究旨在探讨RSV对SAH后大鼠NLRP 3炎性体信号通路和EBI的作用。建立大鼠视交叉前池注射模型，用氧合血红蛋白（oxyHb）刺激原代培养的皮层神经元诱导SAH。结果表明，SAH后NLRP 3炎性体组分表达上调，包括NLRP 3、含有caspase募集结构域的凋亡相关斑点样蛋白（ASC）、caspase-1、成熟白细胞介素-1 β（IL-1β）和白细胞介素-18（IL-18），且SAH后NLRP 3表达上调主要位于小胶质细胞。SAH后60或90 mg/kg RSV处理显著抑制NLRP 3的表达，但SAH + 60 mg/kg RSV组和SAH + 90 mg/kg RSV组之间NLRP 3的表达无显著差异。此外，用30 mg/kg RSV处理没有显著降低NLRP 3的表达。我们接下来评估了RSV对SAH的神经保护作用。我们确定SAH诱导的NLRP 3炎性小体活化在SAH + 60 mg/kg RSV组中被显著抑制。60 mg/kg RSV可明显抑制SAH后小胶质细胞的活化和中性粒细胞的浸润。RSV可明显减轻SAH后脑组织炎症反应，减轻SAH后皮质细胞凋亡、脑水肿和神经行为损害。在体外实验中，RSV治疗也明显保护原代皮层神经元免受oxyHb损伤，包括降低神经元凋亡的比例，减轻神经元变性，并提高细胞活力。这些体外数据进一步证实了RSV对SAH具有有效的神经保护作用。综上所述，这些体内和体外研究结果表明，RSV可以保护SAH后的EBI，至少部分通过抑制NLRP 3炎性体信号通路。
Previous studies have demonstrated resveratrol (RSV) has beneficial effects in early brain injury (EBI) after subarachnoid hemorrhage (SAH). However, the beneficial effects of RSV and the underlying mechanisms have not been clearly identified. The nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome activation plays a crucial role in the EBI pathogenesis. The aim of this study was to investigate the role of RSV on the NLRP3 inflammasome signaling pathway and EBI in rats after SAH. A prechiasmatic cistern injection model was established in rats, and the primary cultured cortical neurons were stimulated with oxyhemoglobin (oxyHb) to induce SAH in vitro. It showed that the NLRP3 inflammasome components, including NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), caspase-1, mature interleukin-1β (IL-1β), and interleukin-18 (IL-18) were upregulated after SAH, and the enhanced NLRP3 after SAH was mainly located in microglia. Treatment with 60 or 90 mg/kg RSV after SAH dramatically inhibited the expression of NLRP3, but there was no significant difference in the expression of NLRP3 between the SAH + 60 mg/kg RSV and SAH + 90 mg/kg RSV groups. In addition, treatment with 30 mg/kg RSV did not significantly reduced the expression of NLRP3. We next evaluated the neuroprotective effects of RSV against SAH. We determined that SAH-induced NLRP3 inflammasome activation was significantly inhibited in the SAH + 60 mg/kg RSV group. Meanwhile, 60 mg/kg RSV administration could markedly inhibit microglia activation and neutrophils infiltration after SAH. Concomitant with the decreased cerebral inflammation, RSV evidently reduced cortical apoptosis, brain edema, and neurobehavioral impairment after SAH. In vitro experiments, RSV treatment also clearly protected primary cortical neurons against oxyHb insults, including reduced the proportion of neuronal apoptosis, alleviated neuronal degeneration, and improved cell viabilities. These in vitro data further confirm that RSV has an efficient neuroprotection against SAH. Taken together, these in vivo and in vitro findings suggested RSV could protect against EBI after SAH, at least partially via inhibiting NLRP3 inflammasome signaling pathway.
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DOI：
10.1042/bj20081386
发表时间：
2009-01-01
期刊：
The Biochemical journal
影响因子：
--
作者：
Murphy MP
通讯作者：
Murphy MP
体内和体外实验性蛛网膜下腔出血神经元早期释放高迁移率族盒 1 (HMGB1)。
影响因子：
9.3
作者：
Sun Q;Wu W;Hu YC;Li H;Zhang D;Li S;Li W;Li WD;Ma B;Zhu JH;Zhou ML;Hang CH
通讯作者：
Hang CH
影响因子：
5.1
作者：
Sehba, Fatima A.;Pluta, Ryszard M.;Zhang, John H.
通讯作者：
Zhang, John H.
影响因子：
3.3
作者：
Della-Morte, D.;Dave, K. R.;Defazio, R. A.;Bao, Y. C.;Raval, A. P.;Perez-Pinzon, M. A.
通讯作者：
Perez-Pinzon, M. A.
DOI：
10.1016/j.bbi.2016.12.012
发表时间：
2017-03
期刊：
Brain, behavior, and immunity
影响因子：
--
作者：
Lan X;Han X;Li Q;Li Q;Gao Y;Cheng T;Wan J;Zhu W;Wang J
通讯作者：
Wang J