Abstract：
Neuroinflammation is implicated in the onset of postoperative cognitive dysfunction (POCD), with CD33 and triggering receptor expressed on myeloid cells 2 (TREM2) playing crucial roles in immune response modulation and neuroinflammatory processes. A total of 96 aged male C57/BL6 mice (9-12 months) were randomly assigned to one of four groups, each receiving an siRNA injection into the lateral ventricle. Subsequently, the mice underwent partial hepatectomy under general anesthesia. To assess cognitive function, the Morris water maze tests were conducted both pre- and post-surgery. Following behavioral assessments, hippocampal tissues were swiftly harvested. The regulation of CD33 and TREM2 expression was achieved through siRNA in the BV2 microglia cell line. Expression levels of CD33 and TREM2 were evaluated both in vitro and in vivo using quantitative RT-PCR and western blot analyses. This study explored the impact of CD33 and TREM2 on POCD in aged mice and revealed that surgery and anesthesia increased CD33 expression, leading to spatial learning and memory impairments. Inhibiting CD33 expression via siRNA administration ameliorated cognitive deficits and mitigated the neuroinflammatory response triggered by surgery. Additionally, CD33 inhibition reversed the surgery-induced decrease in synaptic-related proteins, highlighting its role in preserving synaptic integrity. Moreover, our experiments suggest that CD33 may influence neuroinflammation and cognitive function through mechanisms involving TREM2. This is evidenced by the suppression of pro-inflammatory cytokines following CD33 knockdown in microglia and the reversal of these effects when both CD33 and TREM2 are concurrently knocked down. These findings imply that CD33 might promote neuroinflammation by inhibiting TREM2. This study highlights the potential of targeting CD33 as a promising therapeutic strategy for preventing and treating POCD. It provides valuable insights into the intricate mechanisms underlying cognitive dysfunction following surgical procedures.
摘要：
神经炎症与术后认知功能障碍（POCD）的发作有关，CD33和髓样细胞2上表达的触发受体（TREM2）在免疫反应调节和神经炎性过程中起着至关重要的作用。将96只雄性C57/BL6小鼠（9-12个月）随机分为四组，每个接受siRNA注射到侧脑室。随后，小鼠在全身麻醉下接受部分肝切除术。为了评估认知功能，Morris水迷宫试验在手术前和手术后进行.在行为评估之后，迅速收获海马组织。通过siRNA在BV2小胶质细胞中实现对CD33和TREM2表达的调控。使用定量RT-PCR和蛋白质印迹分析在体外和体内评估CD33和TREM2的表达水平。这项研究探索了CD33和TREM2对老年小鼠POCD的影响，并揭示了手术和麻醉增加了CD33的表达。导致空间学习和记忆障碍。通过siRNA施用抑制CD33表达改善了认知缺陷并减轻了由手术引发的神经炎症反应。此外,CD33抑制逆转了手术诱导的突触相关蛋白的减少，强调其在保持突触完整性方面的作用。此外，我们的实验提示CD33可能通过涉及TREM2的机制影响神经炎症和认知功能.这通过小胶质细胞中CD33敲低后促炎细胞因子的抑制和当CD33和TREM2同时敲低时这些作用的逆转来证明。这些发现暗示CD33可能通过抑制TREM2促进神经炎症。这项研究强调了靶向CD33作为预防和治疗POCD的有希望的治疗策略的潜力。它为外科手术后认知功能障碍的复杂机制提供了有价值的见解。
