Department of Neurosurgery, The Second Affiliated Hospital of Jiaxing University, Jiaxing, China.
Department of Neurology, The Second Affiliated Hospital of Jiaxing University, Jiaxing, China.
Mol Neurobiol. 2024 Apr;61(4):2459-2467. doi: 10.1007/s12035-023-03729-6. Epub 2023 Oct 28.
The present work aimed to explore the role of long non-coding RNA (lncRNA)-AC020978 in postoperative cognitive disorder (POCD) and the underlying mechanism. The POCD mouse model was constructed through isoflurane anesthesia + abbreviated laparotomy. The AC020978 expression in brain tissue was silenced after lentivirus injection, then Morris water maze test was conducted to detect the cognitive disorder level, flow cytometry was performed to analyze M1 macrophage level, ELISA was carried out to measure inflammatory factor levels, H&E, Nissl and immunohistochemical staining was performed to detect the pathological changes in brain tissue, and Western blotting assay was adopted to detect protein expression. In addition, microglial cells were cultured in vitro, after lentivirus infection, the effect of AC020978 on the M1 polarization of microglial cells and glycolysis was observed. AC020978 overexpression promoted POCD progression and aggravated cognitive disorder in mice; in addition, the proportion of peripheral and central M1 cells increased, the inflammatory factor levels were upregulated, and microglial cells were activated. By contrast, AC020978 silencing led to cognitive disorder in mice and suppressed microglial cell activation and M1 polarization. In vitro experimental results indicated that AC020978 promoted the expression and phosphorylation of PKM2, which promoted inflammatory response through enhancing microglial cell glycolysis and M1 polarization. AC020978 interacts with PKM2 to promote the glycolysis and M1 polarization of microglial cells, thus regulating cognitive disorder and central inflammation in POCD.
本研究旨在探讨长链非编码 RNA (lncRNA)-AC020978 在术后认知障碍 (POCD) 中的作用及其潜在机制。通过异氟烷麻醉 + 简化剖腹术构建 POCD 小鼠模型。通过慢病毒注射沉默脑组织中的 AC020978 表达，然后进行 Morris 水迷宫测试以检测认知障碍水平，通过流式细胞术分析 M1 巨噬细胞水平，通过 ELISA 测定炎症因子水平，通过 H&E、Nissl 和免疫组织化学染色检测脑组织的病理变化，通过 Western blot 检测蛋白表达。此外，在体外培养小胶质细胞，通过慢病毒感染，观察 AC020978 对小胶质细胞 M1 极化和糖酵解的影响。AC020978 的过表达促进了 POCD 的进展，并加重了小鼠的认知障碍；此外，外周和中枢 M1 细胞的比例增加，炎症因子水平上调，小胶质细胞被激活。相比之下，AC020978 的沉默导致了小鼠的认知障碍，并抑制了小胶质细胞的激活和 M1 极化。体外实验结果表明，AC020978 促进了 PKM2 的表达和磷酸化，通过增强小胶质细胞糖酵解和 M1 极化促进了炎症反应。AC020978 与 PKM2 相互作用，促进小胶质细胞的糖酵解和 M1 极化，从而调节 POCD 中的认知障碍和中枢炎症。
