目的 探索间充质干细胞来源外泌体（mesenchymal stem cell-derived exosome, MSC-Exo）是否通过靶向核苷酸结合寡聚化结构域样受体蛋白3（nucleotide-binding oligomerization domain-like receptor protein 3, NLRP3）减轻新生大鼠脑白质损伤（white matter damage, WMD）。 方法 将3日龄Sprague-Dawley大鼠随机分为假手术组、缺氧缺血（hypoxia-ischemia, HI）组、MSC-Exo组及MCC950（NLRP3抑制剂）组（n=24）。采用单侧颈总动脉结扎联合缺氧法构建WMD模型，脑立体定位仪辅助侧脑室移植外泌体（1×10⁸粒子/μL）。建模后14 d，通过苏木精-伊红染色观察脑组织病理变化，透射电镜观察有髓鞘轴突的表达情况，蛋白质印迹法检测髓鞘碱性蛋白（myelin basic protein, MBP）、NLRP3、半胱天冬酶-1（cysteine-dependent aspartate-specific protease 1, caspase-1）及白细胞介素-1β（interleukin-1β, IL-1β）蛋白表达，免疫组化检测NLRP3、caspase-1、IL-1β表达；建模后28 d，利用Morris水迷宫检测各组大鼠行为学变化。 结果 HI组可见炎性细胞浸润、大量空泡结构，有髓鞘轴突数量较假手术组减少；与HI组相比，MSC-Exo组炎性细胞浸润减轻，仅见少量空泡结构，有髓鞘轴突数量增加；MCC950组细胞形态基本恢复正常。与假手术组相比，HI组MBP蛋白表达水平、平台穿越次数、目标象限停留时间减少（P<0.05），NLRP3、caspase-1、IL-1β阳性表达和蛋白表达水平、逃避潜伏期增加（P<0.05）；与HI组相比，MSC-Exo组和MCC90组MBP蛋白表达水平、平台穿越次数、目标象限停留时间增加（P<0.05），NLRP3、caspase-1、IL-1β阳性表达和蛋白表达水平、逃避潜伏期减少（P<0.05）。 结论 MSC-Exo可通过靶向NLRP3炎症小体及促进少突胶质细胞成熟，减轻新生大鼠WMD。

Objective To investigate whether mesenchymal stem cell-derived exosomes (MSC-Exo) alleviate white matter damage (WMD) in neonatal rats by targeting the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3). Methods Three-day-old Sprague-Dawley rats were randomly assigned to four groups: Sham, hypoxia-ischemia (HI), MSC-Exo, and MCC950 (NLRP3 inhibitor) (n=24 per group). The WMD model was established by unilateral common carotid artery ligation combined with hypoxia. Exosomes (1×10⁸ particles/μL) were transplanted into the lateral ventricle using stereotaxic guidance. Fourteen days after modeling, hematoxylin-eosin staining was used to observe pathological changes in brain tissue, and transmission electron microscopy was used to assess myelinated axons. Western blotting was performed to detect the expression of myelin basic protein (MBP), NLRP3, caspase-1, and interleukin-1β (IL-1β). Immunohistochemistry was used to measure NLRP3, caspase-1, and IL-1β expression. Twenty-eight days post-modeling, behavioral changes were evaluated using the Morris water maze. Results In the HI group, marked inflammatory cell infiltration, extensive vacuolation, and decreased numbers of myelinated axons were observed compared to the Sham group. The MSC-Exo group showed reduced inflammatory infiltration, fewer vacuoles, and increased myelinated axons compared to the HI group, while the MCC950 group showed nearly normal cell morphology. Compared to the Sham group, the HI group exhibited decreased MBP expression, fewer platform crossings, shorter time in the target quadrant, increased expression of NLRP3, caspase-1, and IL-1β, and longer escape latency (all P<0.05). Compared to the HI group, the MSC-Exo and MCC950 groups showed increased MBP expression, more platform crossings, longer target quadrant stay, and reduced NLRP3, caspase-1, and IL-1β expression, as well as shorter escape latency (all P<0.05). Conclusions MSC-Exo may attenuate white matter damage in neonatal rats by targeting the NLRP3 inflammasome and promoting oligodendrocyte maturation.