Neonatal hypoxic-ischemic encephalopathy (HIE) is one of the main causes of neonatal disability and death. As a derivative of N-acetylserotonin, N-[2-(5-hydroxy-1H-indol-3-yl) ethyl]-2-oxopiperidine-3-carboxamide (HIOC) can easily cross the blood–brain barrier and have a long half-life in the brain. In this study, the hypothesis was verified that HIOC plays a neuroprotective role in the HIE model and its potential mechanism was evaluated. Firstly, an HIE rat model was established to deliver HIOC, revealing that it can reduce cerebral infarction volume, cerebral edema, and neuronal apoptosis. The results of immunofluorescence staining, Western blots and RT-PCR further showed that HIOC could inhibit the activation of the NLRP3 inflammasome and the expression of related proteins. Finally, the activation of the phosphatidylinositol-3-kinase (PI3K)/Akt/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway by HIOC was verified in vitro and in vivo. It was discovered that HIOC could increase the nuclear translocation of Nrf2, and that this induction can be reversed by the PI3K/Akt pathway inhibitor LY294002. In general terms, the neuroprotective effect of HIOC was confirmed in the HIE model, which is related to the activation of the Pi3k/Akt/Nrf2 signal pathway and the inhibition of the NLRP3 inflammasome.

新生儿缺氧缺血性脑病（HIE）是导致新生儿残疾和死亡的主要原因之一。作为N-乙酰血清素的衍生物，N-[2-(5-hydroxy-1H-indol-3-yl) ethyl]-2-oxopiperidine-3-carboxamide (HIOC) 很容易穿过血脑屏障，具有在大脑中的半衰期很长。在这项研究中，验证了 HIOC 在 HIE 模型中发挥神经保护作用的假设，并评估了其潜在机制。首先，建立HIE大鼠模型给予HIOC，揭示其可以减少脑梗死体积、脑水肿和神经元凋亡。免疫荧光染色、Western blots和RT-PCR结果进一步表明HIOC能够抑制NLRP3炎性体的激活和相关蛋白的表达。最后，. 发现 HIOC 可以增加 Nrf2 的核转位，并且这种诱导可以被 PI3K/Akt 通路抑制剂 LY294002 逆转。一般来说，HIOC 的神经保护作用在 HIE 模型中得到证实，这与 Pi3k/Akt/Nrf2 信号通路的激活和 NLRP3 炎性体的抑制有关。