Resolvin D1 Attenuates Innate Immune Reactions in Experimental Subarachnoid Hemorrhage Rat Model
Resolvin D1 Attenuates Innate Immune Reactions in Experimental Subarachnoid Hemorrhage Rat Model
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Resolvin D1 减弱实验性蛛网膜下腔出血大鼠模型中的先天免疫反应
DOI：
10.1007/s12035-020-02237-1
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发表时间：
2021-01-07
影响因子：
5.1
通讯作者：
Li, Wei
中科院分区：
文献类型：
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作者：
Liu, Guang-Jie;Tao, Tao;Li, Wei
过度炎症是导致早期脑损伤(EBI)的主要原因，并与蛛网膜下腔出血(SAH)的阴性或灾难性后果有关。RvD1对各种原因引起的急性或慢性炎症均有较强的抗炎和促消退作用。从此以后，我们假设RvD1有可能减轻SAH后EBI中的过度炎症。因此，我们建立了细丝穿孔SAH模型，并在实验性SAH后给予3种不同剂量(0.3、0.6和1.2nmoL)的RvD1。用组织病理学或免疫荧光染色、免疫印迹和定量聚合酶链式反应观察中性粒细胞的浸润、神经元的死亡和小胶质细胞的致炎极化。在确认RvD1对SAH的作用后，我们在SAH建立前30min给予FPR2特异性拮抗剂Trp-Arg-Trp-NH2(WRW4)，观察该化合物是否能取消RvD1的抗炎作用。综上所述，我们的结果表明，RvD1具有较强的抗炎作用，并显著减少中性粒细胞的浸润和小胶质细胞的促炎活性，导致神经功能和脑组织修复的显著改善。加入WRW4后，RvD1的抗炎作用消失。这些结果表明，RvD1具有良好的抗炎作用和减轻EBI的作用，提示RvD1可能是治疗SAH损伤的一种新的治疗方法。
Excessive inflammation is a major cause contributing to early brain injury (EBI) and is associated with negative or catastrophic outcomes of subarachnoid hemorrhage (SAH). Resolvin D1 (RvD1) exerts strong anti-inflammatory and pro-resolving effects on either acute or chronic inflammation of various origin. Henceforth, we hypothesized that RvD1 potentially attenuates excessive inflammation in EBI following SAH. Therefore, we generated a filament perforation SAH model and administered 3 different doses (0.3, 0.6, and 1.2 nmol) of RvD1 after experimental SAH. Neurological scores, brain edema, and blood–brain barrier integrity were evaluated; besides, neutrophil infiltration, neuronal deaths, and microglial pro-inflammatory polarization were observed using histopathology or immunofluorescence staining, western blots, and qPCR. After confirming the effectiveness of RvD1 in SAH, we administered the FPR2-specific antagonist Trp-Arg-Trp-Trp-Trp-Trp-NH2 (WRW4) 30 min before SAH establishment to observe whether this compound could abolish the anti-inflammatory effect of RvD1. Altogether, our results showed that RvD1 exerted a strong anti-inflammatory effect and markedly reduced neutrophil infiltration and microglial pro-inflammatory activation, leading to remarkable improvements in neurological function and brain tissue restoration. After addition of WRW4, the anti-inflammatory effects of RvD1 were abolished. These results indicated that RvD1 could exert a good anti-inflammatory effect and alleviate EBI, which suggested that RvD1 might be a novel therapeutic alternative for SAH-induced injury.