Xin Xi, Zhang Haonan, Yang Chenyi, Wang Xinyi, Zhang Lin, Ma Ji, Wang Haiyun
The Third Central Clinical College of Tianjin Medical University, Tianjin, China.
Department of Anesthesiology, Tianjin University Central Hospital, Tianjin, China.
Front Immunol. 2025 Aug 21;16:1650254. doi: 10.3389/fimmu.2025.1650254. eCollection 2025.
Perioperative 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.
This 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.
The 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.
The 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.
围手术期神经认知障碍（PND）是一种重要的临床综合征，神经炎症是其重要的病理过程。基质金属蛋白酶9（MMP9）作为一种锌离子依赖性基质酶，不仅维持血脑屏障的完整性和突触可塑性，还在周围和中枢神经炎症中起关键调节因子的作用。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的神经炎症的影响，并为PND的预防和治疗提供新的靶点。
本研究采用腹腔注射MMP9抑制剂SB-3CT来阻断MMP9的作用。通过莫里斯水迷宫和新物体识别测试评估行为表现。采用蛋白质免疫印迹法检测海马炎性因子。利用免疫荧光和流式细胞术检测小胶质细胞表型的转变。
研究结果表明，手术干预导致老年大鼠学习和记忆能力显著受损，同时伴有MMP9表达升高、海马炎症加剧以及以M1表型为主导的小胶质细胞极化。给予SB-3CT可有效逆转这些病理表现。
抑制MMP9可通过调节小胶质细胞极化和减轻神经炎症来增强神经功能，这是高危PND患者围手术期神经保护的一种新方法。
