Department of Anesthesiology, 543160the Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, China.
Department of General Surgery, 543160the Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, China.
Hum Exp Toxicol. 2022 Jan-Dec;41:9603271211061497. doi: 10.1177/09603271211061497.
As a common postoperative complication to elderly patients, postoperative cognitive dysfunction (POCD) is a central nervous system complication, often taking place after anesthesia and surgery. (Su(var)3-9, enhancer-of-zeste, and trithorax) domain-containing protein 7 (SETD7) plays important roles in metabolic-related diseases, viral infections, tumor formation, and some inflammatory reactions. However, the role and mechanism of SETD7 in POCD have not been previously studied.
RT-PCR and Western blot were performed to evaluate the efficiency of knockdown of SETD7. The pathological changes of hippocampal neurons in isoflurane-anesthetized mice were detected by HE staining, and the Morris water maze experiment was performed to evaluate the learning and memory abilities of mice. The effect of SETD7 on the hippocampus in isoflurane-induced aged mice was examined by Western blot and TUNEL assay. Then ELISA assay was applied to determine the expression of some inflammatory cytokines, followed by the detection of expression of NOD-like receptor protein 3 (NLRP3) inflammasome through Western blot.
The data of this research revealed that SETD7 knockdown improved cognitive impairment in isoflurane-anesthetized mice, ameliorated cell pyroptosis, inhibited the release of inflammatory cytokines, and suppressed the activation of NLRP3 inflammasome in the hippocampus in isoflurane-induced aged mice.
Collectively, these results provided evidence that the inhibition of SETD7 could alleviate neuroinflammation, pyroptosis, and cognitive impairment by suppressing the activation of the NLRP3 inflammasome in isoflurane-induced aged mice.
术后认知功能障碍（POCD）是一种中枢神经系统并发症，作为老年患者的一种常见术后并发症，常发生于麻醉和手术后。（Su(var)3-9、增强子的锌指蛋白和三价体）结构域蛋白 7（SETD7）在代谢相关疾病、病毒感染、肿瘤形成和某些炎症反应中发挥重要作用。然而，SETD7 在 POCD 中的作用和机制尚未被研究过。
通过 RT-PCR 和 Western blot 评估 SETD7 敲低的效率。通过 HE 染色检测异氟烷麻醉小鼠海马神经元的病理变化，通过 Morris 水迷宫实验评估小鼠的学习和记忆能力。通过 Western blot 和 TUNEL 检测评估 SETD7 对异氟烷诱导的老年小鼠海马的影响。然后应用 ELISA 测定一些炎性细胞因子的表达，接着通过 Western blot 检测 NOD 样受体蛋白 3（NLRP3）炎性小体的表达。
这项研究的数据表明，SETD7 敲低可改善异氟烷麻醉小鼠的认知障碍，改善细胞焦亡，抑制炎性细胞因子的释放，并抑制异氟烷诱导的老年小鼠海马中 NLRP3 炎性小体的激活。
综上所述，这些结果表明抑制 SETD7 可通过抑制 NLRP3 炎性小体的激活来减轻神经炎症、细胞焦亡和认知障碍。
