PDF(Pubmed)
Abstract：
Postoperative cognitive dysfunction (POCD) is a common postoperative complication in elderly patients, and neuroinflammation is a key hallmark. Recent studies suggest that the NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome-mediated astrocytes pyroptosis is involved in the regulation of neuroinflammation in many neurocognitive diseases, while its role in POCD remains obscure. Carnosine is a natural endogenous dipeptide with anti-inflammatory and neuroprotective effects. To explore the effect of carnosine on POCD and its mechanism, we established a POCD model by exploratory laparotomy in 24-month-old male Sprague-Dawley rats. We found that the administrated of carnosine notably attenuated surgery-induced NLRP3 inflammasome activation and pyroptosis in astrocytes, central inflammation, and neuronal damage in the hippocampus of aged rats. In addition, carnosine dramatically ameliorated the learning and memory deficits of surgery-induced aged rats. Then in the in vitro experiments, we stimulated primary astrocytes with lipopolysaccharide (LPS) after carnosine pretreatment. The results also showed that the application of carnosine alleviated the activation of the NLRP3 inflammasome, pyroptosis, and inflammatory response in astrocytes stimulated by LPS. Taken together, these findings suggest that carnosine improves POCD in aged rats via inhibiting NLRP3-mediated astrocytes pyroptosis and neuroinflammation.
摘要：
术后认知功能障碍(POCD)是老年患者术后常见的并发症,神经炎症是一个关键标志。最近的研究表明，NOD样受体家族，含pyrin结构域3（NLRP3）炎症小体介导的星形胶质细胞焦凋亡参与许多神经认知疾病中神经炎症的调节，虽然它在POCD中的作用仍然模糊。肌肽是一种具有抗炎和神经保护作用的天然内源性二肽。探讨肌肽对POCD的作用及其机制,我们通过探查性剖腹手术在24个月大的雄性Sprague-Dawley大鼠中建立了POCD模型。我们发现肌肽显著减弱了手术诱导的星形胶质细胞NLRP3炎性体活化和细胞凋亡,中枢炎症,老年大鼠海马神经元损伤。此外,肌肽显著改善了手术诱导的老年大鼠的学习和记忆障碍。然后在体外实验中，肌肽预处理后，我们用脂多糖（LPS）刺激原代星形胶质细胞。结果还表明，肌肽的应用减轻了NLRP3炎性体的活化，焦亡,和LPS刺激的星形胶质细胞的炎症反应。一起来看,这些发现表明，肌肽通过抑制NLRP3介导的星形胶质细胞焦凋亡和神经炎症改善老年大鼠的POCD。
