Zhang Qi, Li Yanan, Wang Xupeng, Yin Chunping, Zhou Qi, Guo Junfei, Zhao Juan, Xian Xiaohui, Hou Zhiyong, Wang Qiujun
Department of Anesthesiology, Children's Hospital of Hebei Province Affiliated to Hebei Medical University, Shijiazhuang, China.
Department of Anesthesiology, The Third Hospital of Hebei Medical University, Shijiazhuang, China.
Front Aging Neurosci. 2022 Oct 20;14:990679. doi: 10.3389/fnagi.2022.990679. eCollection 2022.
The role of the inositol 1, 4, 5-trisphosphate receptor (IP3R) in hippocampal neuronal apoptosis and cognitive dysfunction induced by sevoflurane is currently unclear. Therefore, in this study, we investigated the role of the IP3R in endoplasmic reticulum (ER) stress and hippocampal neuronal apoptosis induced by sevoflurane in aged rats and isolated hippocampal neurons using both and experiments, including bioinformatics, functional enrichment analysis, gene set enrichment analysis, hematoxylin, and eosin staining, TUNEL assay, flow cytometry, western blot analysis and transmission electron microscopy. Furthermore, behavioral assessment was performed with the Morris water maze test. We identified 232 differentially expressed genes induced by sevoflurane exposure, including 126 upregulated genes and 106 downregulated genes. Sevoflurane exposure caused cognitive impairment and neuronal injury, and increased p-IP3R levels and ER stress. An IP3R inhibitor, 2-APB, suppressed these changes, while an IP3R agonist, FK-506, aggravated these changes. Together, these findings suggest that sevoflurane exposure causes marked cognitive dysfunction in aged rats and neuronal injury in isolated hippocampal neurons by activating the IP3R and inducing cytoplasmic calcium overload, thereby resulting in ER stress and hippocampal neuronal apoptosis. GRAPHICAL ABSTRACT.
目前尚不清楚1,4,5-三磷酸肌醇受体（IP3R）在七氟醚诱导的海马神经元凋亡和认知功能障碍中的作用。因此，在本研究中，我们使用生物信息学、功能富集分析、基因集富集分析、苏木精和伊红染色、TUNEL检测、流式细胞术、蛋白质免疫印迹分析和透射电子显微镜等体内和体外实验，研究了IP3R在七氟醚诱导的老年大鼠和分离的海马神经元内质网（ER）应激和海马神经元凋亡中的作用。此外，用莫里斯水迷宫试验进行行为评估。我们鉴定出七氟醚暴露诱导的232个差异表达基因，包括126个上调基因和106个下调基因。七氟醚暴露导致认知障碍和神经元损伤，并增加p-IP3R水平和内质网应激。IP3R抑制剂2-APB可抑制这些变化，而IP3R激动剂FK-506则加剧这些变化。总之，这些发现表明，七氟醚暴露通过激活IP3R并诱导细胞质钙超载，导致老年大鼠明显的认知功能障碍和分离的海马神经元损伤，从而导致内质网应激和海马神经元凋亡。图形摘要。
