Resveratrol ameliorates sevoflurane-induced cognitive impairment by activating the SIRT1/NF-κB pathway in neonatal mice
Resveratrol ameliorates sevoflurane-induced cognitive impairment by activating the SIRT1/NF-κB pathway in neonatal mice
复制标题
白藜芦醇通过激活新生小鼠SIRT1/NF-κB通路改善七氟醚诱导的认知功能障碍
DOI：
10.1016/j.jnutbio.2020.108579
复制
发表时间：
2021-01-14
影响因子：
5.6
通讯作者：
Li, Shi Yong
中科院分区：
文献类型：
--
作者：
Tang, Xiao Le;Wang, Xuan;Li, Shi Yong
七氟醚是儿科麻醉中最常用的吸入麻醉剂，据报道，在临床前和临床环境中，七氟醚会导致发育中的大脑认知障碍。然而，这种发育神经毒性的机制和治疗措施还需要进一步的研究。白藜芦醇是一种天然的多酚类药物，已有报道通过抗炎活性改善神经疾病和衰老模型的认知功能。然而，它对七氟醚引起的发育中小鼠认知障碍的影响尚不清楚。本研究旨在探讨白藜芦醇对七氟醚所致认知功能障碍的治疗作用。6日龄小鼠在出生后第6天、第7天和第8天每天用3%七氟醚麻醉2小时。新生小鼠麻醉前连续6d腹腔注射白藜芦醇约100 mg/kg。七氟醚可显著抑制Sirtuin 1(SIRT1)的表达，激活小胶质细胞。此外，七氟醚暴露后，白介素6(IL-6)和肿瘤坏死因子-α(TNF-α)水平显著升高。值得注意的是，白藜芦醇可改善七氟醚诱导的SIRT1抑制和小胶质细胞激活。值得注意的是，白藜芦醇逆转了七氟醚诱导的M1/M2小胶质细胞比例失衡，表现为增加分化簇206(CD206)的mRNA水平，降低分化簇86(CD86)和细胞因子信号抑制因子3(SOCS3)的mRNA水平。因此，白藜芦醇预处理可改善七氟醚所致的发育中小鼠的认知障碍。综上所述，七氟醚反复暴露于发育中的大脑导致SIRT1抑制、核因子-kappa B乙酰化和小胶质细胞激活。白藜芦醇通过调节小胶质细胞中SIRT1NF-kappaB通路改善七氟醚暴露小鼠的认知功能障碍。在这方面，我们的发现为探索预防七氟醚发育神经毒性的有前景的治疗靶点开辟了新的方向。(C)2020 Elsevier Inc.保留所有权利。
Sevoflurane, the most commonly used inhaled anesthetic in pediatric anesthesia, has been reported to induce cognitive impairment in developing brain in preclinical and clinical settings. However, the mechanism and therapeutic measures of this developmental neurotoxicity need to be further investigated. Resveratrol, a natural polyphenolic agent, has been reported to improve cognitive function in neurological disorders and aging models through anti-inflammatory activity. However, its effect on sevoflurane-induced cognitive impairment in developing mice remains unknown. The present study was designed to investigate the therapeutic potential of resveratrol on sevoflurane-induced cognitive impairment. Six-day-old mice received anesthesia with 3% sevoflurane 2 h daily on postnatal days (P) 6, P7 and P8. About 100 mg/kg resveratrol were intraperitoneally administered for 6 consecutive days to neonatal mice before anesthesia. Sevoflurane exposure significantly suppressed the expression of Sirtuin 1 (SIRT1) and activated microglia in hippocampi. Furthermore, the levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) were markedly increased after sevoflurane exposure. Strikingly, resveratrol pretreatment ameliorated sevoflurane-induced SIRT1 inhibition and microglial activation. Of note, resveratrol reversed sevoflurane-induced imbalance of M1/M2 microglia ratio revealed by increasing mRNA level of clusters of differentiation 206 (CD206) and decreasing mRNA levels of clusters of differentiation 86 (CD86) and suppressor of cytokine signaling 3 (SOCS3). Consequently, sevoflurane-induced cognitive impairment in developing mice was ameliorated by resveratrol pretreatment. Taken together, repeated sevoflurane exposure to the developing brain resulted in SIRT1 inhibition, NF-kappa B acetylation, and microglial activation. Resveratrol pretreatment ameliorated cognitive impairment in developing mice received sevoflurane exposure by modulating SIRT1NF-kappa B pathway in microglia. In this regard, our findings open novel directions to explore promising therapeutic targets for preventing the developmental neurotoxicity of sevoflurane. (C) 2020 Elsevier Inc. All rights reserved.