Objective: The possible effect of NMDAR (N-methyl-D-aspartate receptor)-NMNAT1/2 (nicotinamide/nicotinic acid mono-nucleotide adenylyltransferase) signaling pathway on the neuronal cell damage and cognitive impairment of aged rats anesthetized by sevoflurane was explored.Methods: Adult male Wistar rats were selected and divided into Control, Sevo (Sevoflurane), Sevo+DCS (NMDAR agonist D-cycloserine) 30 mg/kg, Sevo+DCS 100 mg/kg, and Sevo+DCS 200 mg/kg groups. Morris water maze and fear conditioning text were used to observe cognitive function changes of rats. The inflammatory cytokines were determined by quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) assay, neuronal apoptosis by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labelling (TUNEL) staining and MDAR-NMNAT1/2 pathway-related proteins by Western blotting.Results: The longer escape latency, decreased platform crossing times and reduced staying time spent in platform quadrant were found in rats from Sevo group, with decreased percentage of freezing time in contextual test and tone cued test; and meanwhile, these rats had increased inflammatory cytokines (interleukin (IL)-1β, tumor necrosis factor (TNF-α), IL-6, and IL-8) and neuronal apoptosis, but declined expressions of MDAR-NMNAT1/2 pathway-related proteins. However, the above changes were exhibited an opposite tendency in those Sevo rats treated with different concentrations of DCS (including 30, 100, and 200 mg/kg, respectively). Particularly, the improving effect of low-dose DCS on each aspect in aged rats was better than high-dose ones.Conclusion: Activation of NMDAR-NMNAT1/2 signaling pathway could not only reduce neuronal apoptosis, but also alleviate sevoflurane-induced neuronal inflammation and cognitive impairment in aged rats.

中文翻译：

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NMDAR-NMNAT1 / 2途径对七氟醚致衰老大鼠神经细胞损伤和认知障碍的影响。

目的：探讨NMDAR（N-甲基-D-天冬氨酸受体）-NMNAT1 / 2（烟酰胺/烟酸单核苷酸腺苷酸转移酶）信号通路对七氟醚麻醉的老年大鼠神经元细胞损伤和认知障碍的可能作用。方法：选择成年雄性Wistar大鼠，分为对照组，Sevo（Sevoflurane），Sevo + DCS（NMDAR激动剂D-环丝氨酸）30 mg / kg，Sevo + DCS 100 mg / kg和Sevo + DCS 200 mg / kg组。莫里斯水迷宫和恐惧条件文本被用来观察大鼠的认知功能变化。通过定量实时聚合酶链反应（qRT-PCR）和酶联免疫吸附测定（ELISA）测定确定炎性细胞因子，末端脱氧核苷酸转移酶（TdT）介导的dUTP缺口末端标记（TUNEL）染色和MDAR-NMNAT1 / 2途径相关的蛋白质通过Western印迹检测神经元凋亡。结果：更长的逃逸潜伏期，减少了平台穿越时间并减少了停留时间Sevo组大鼠在平台象限中发现，在上下文测试和语调提示测试中冻结时间的百分比降低；同时，这些大鼠的炎症细胞因子（白介素（IL）-1β，肿瘤坏死因子（TNF-α），IL-6和IL-8）增多和神经元凋亡，但MDAR-NMNAT1 / 2通路的表达却降低了。相关蛋白质。但是，在用不同浓度的DCS（分别包括30、100和200 mg / kg）处理的那些Sevo大鼠中，上述变化表现出相反的趋势。尤其，