目的 采用非暴露式气管滴注建立不同剂量氧化钕暴露小鼠模型，研究氧化钕暴露致小鼠脑组织损伤的机制。 方法 将48只雄性C57/BL6小鼠随机分为四组：对照组、低剂量组、中剂量组、高剂量组。低剂量组、中剂量组、高剂量组分别采用非暴露式气管滴注62.5、125、250 mg/mL氧化钕，对照组采用相同给药方式给予等体积生理盐水，35 d后处死小鼠取脑组织。应用RT-PCR检测Claudin-5、Occludin的mRNA表达变化，应用Western blot检测脑组织中Claudin-5、Occludin紧密连接蛋白的表达变化以及MMP-2、MMP-9的表达变化，检测RhoA/ROCK2信号通 路及下游cofilin蛋白的表达，试剂盒法检测MDA、T-AOC、NO氧化应激指标的变化。 结果 中剂量组和高剂量组Claudin-5的mRNA表达较对照组降低（P < 0.05）；低剂量组、中剂量组、高剂量组Occludin 的mRNA表达较对照组降低（P < 0.05）；低剂量组、中剂量组、高剂量组Claudin-5、MMP-2、Occludin的蛋白表达较对照组降低（P < 0.05）；中剂量组和高剂量组MMP-9、RhoA的蛋白表达较对照组降低（P < 0.05）；高剂量组ROCK2、p-cofilin的蛋白表达较对照组降低（P < 0.05）；中剂量组和高剂量组MDA含量较对照组升高（P < 0.05）；中剂量组和高剂量组T-AOC含量较对照组降低（P < 0.05）；高剂量组NO含量较对照组升高（P < 0.05）。 结论 氧化钕暴露导致小鼠血脑屏障通透性增加，引起氧化应激和炎症反应，激活RhoA/ROCK2信号通路。

Objective To establish mouse models exposed to different doses of neodymium oxide via tracheal instillation， and to investigate the mechanisms underlying brain tissue damage induced by neodymium oxide exposure in mice. Methods Forty?eight male C57/BL6 mice were randomly assigned to four groups： the control group， the low?dose group， the medium?dose group， and the high?dose group. The low?dose， medium?dose， and high?dose groups received 62.5 mg/mL， 125 mg/mL， and 250 mg/mL neodymium oxide， respectively， via non?exposed tracheal instillation. The control group received an equivalent volume of saline using the same administration method. After 35 days， the mice were euthanized， and brain tissues were collected. RT?PCR was used to assess the mRNA expression changes of Claudin?5 and Occludin. Western blot analysis was performed to evaluate the expression changes of Claudin?5 and Occludin tight junction proteins， as well as the expression changes of MMP?2 and MMP?9 in the brain tissues. Additionally， the expression of the RhoA/ROCK2 signaling pathway and downstream cofilin protein was examined. Changes in oxidative stress markers， including MDA， T?AOC， and NO， were measured using a kit method. Results The mRNA expression of Claudin?5 was significantly reduced in the middle?dose and high?dose groups compared to the control group （P < 0.05）. Similarly， the mRNA expression of Occludin was significantly lower in the low?dose， medium?dose， and high?dose groups compared to the control group （P < 0.05）. Additionally， the protein expression of Claudin?5， MMP?2， and Occludin was significantly decreased in the low?dose， medium?dose， and high?dose groups compared to the control group （P < 0.05）. The protein expression of MMP?9 and RhoA was also significantly lower in the medium?dose and high?dose groups compared to the control group （P < 0.05）. Furthermore， the protein expression of ROCK2 and p?cofilin in the high?dose group was significantly lower than that in the control group （P < 0.05）. The content of MDA and T?AOC was significantly lower in the medium?dose and high?dose groups compared to the control group （P < 0.05）， and the content of NO in the high?dose group was significantly lower than that in the control group （P < 0.05）. Conclusion Exposure to neodymium oxide results in increased permeability of the blood?brain barrier in mice， leading to oxidative stress， inflammatory responses， and activation of the RhoA/ROCK2 signaling pathway.