Table 2_The critical role of matrix metalloproteinase 9-mediated microglial polarization in perioperative neurocognitive disorders of aged rats.docx

BackgroundPerioperative neurocognitive disorders (PND) is a significant clinical syndrome and neuroinflammation is an important pathological process. Matrix metalloproteinase 9 (MMP9) as a Zn2+-dependent matrix enzyme, not only maintains the integrity of the blood-brain barrier and synaptic plasticity, but also plays a key regulatory factor in peripheral and central nervous inflammation. This study aimed to investigate the effects of MMP9-mediated microglial polarization on surgery-induced neuroinflammation in aged rats and to provide novel targets for prevention and treatment of PND.
MethodsThis study utilized an intraperitoneal injection of SB-3CT, an MMP9 inhibitor, to impede the action of MMP9. Morris water maze and novel object recognition test were conducted to assess behavioral performances. Western blot was employed to examine hippocampal inflammatory factors. Immunofuorescence and flow cytometry were used to examine the transformation of microglia phenotype.
ResultsThe findings demonstrated that surgical intervention induced significant impairment in learning and memory performance in aged rats, accompanied by elevated MMP9 expression, exacerbated hippocampal inflammation, and microglial polarization characterized by a predominant M1 phenotype. Administration of SB-3CT effectively reversed these pathological manifestations.
ConclusionThe inhibition of MMP9 can enhance neurological function by modulating the polarization of microglia and alleviating neuroinflammation, which is a new approach for perioperative neuroprotection in high-risk PND patients.

背景 围手术期神经认知障碍（perioperative neurocognitive disorders, PND）是一类重要的临床综合征，而神经炎症是其关键病理过程。基质金属蛋白酶9（matrix metalloproteinase 9, MMP9）作为锌离子依赖性基质酶，不仅能够维持血脑屏障完整性与突触可塑性，还在外周及中枢神经炎症中发挥关键调控作用。本研究旨在探讨MMP9介导的小胶质细胞极化对老年大鼠手术诱导神经炎症的影响，以期为PND的防治提供全新靶点。
方法 本研究通过腹腔注射MMP9抑制剂SB-3CT以阻断MMP9的生物学活性。采用莫里斯水迷宫实验与新物体识别实验评估大鼠行为学表现，通过蛋白质印迹法（Western blot）检测海马组织炎症因子水平，利用免疫荧光与流式细胞术分析小胶质细胞表型转化情况。
结果 研究结果显示，手术干预可导致老年大鼠出现显著的学习记忆功能损伤，同时伴随MMP9表达上调、海马炎症加剧以及以M1表型为主的小胶质细胞极化。给予SB-3CT可有效逆转上述病理改变。
结论 抑制MMP9可通过调控小胶质细胞极化、缓解神经炎症改善神经功能，为高危PND患者的围手术期神经保护提供了全新策略。