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目的观察铁螯合剂去铁胺(DFA)对脑出血(ICH)后小胶质细胞活化的抑制及其继发性神经损伤的保护作用。方法随机将大鼠分为假手术组、ICH组和DFA治疗组,利用胶原酶制备大鼠基底节区ICH模型,术后1 h开始每12 h腹腔注射DFA,共7 d。测定给药后不同时间点血肿周围脑组织的铁离子浓度变化。OX42免疫组织化学染色观察血肿周围脑组织小胶质细胞变化。ELISA方法测定脑组织IL-1β和TNF-α含量变化。神经功能缺失评分和Nissl染色观察DFA处理后大鼠神经功能恢复和神经元丢失情况。结果 ICH后3 d开始,血肿周围脑组织铁离子浓度较假手术组动物显著增高,并可持续至28 d,同时伴随有局部小胶质细胞数量的显著性增加。应用DFA后,显著降低了血肿周围脑组织的铁离子浓度,且小胶质细胞的数量显著减少,活化小胶质细胞分泌的神经毒性细胞因子IL-1β和TNF-α含量显著降低。同时,血肿周围组织神经元的丢失显著减少,神经功能缺失评分显著降低。结论 ICH后血肿持续释放的铁离子可激活局部小胶质细胞,造成继发性脑损伤。DFA通过清除血肿周围脑组织的铁离子,抑制小胶质细胞的过度活化,减少ICH的神经元死亡,从而改善继发性神经功能障碍。
Objective To observe the inhibitory effect of iron chelator deferoxamine (DFA) on microglial activation after intracerebral hemorrhage (ICH) and its protective effect on secondary neuronal injury. Methods The rats were randomly divided into sham operation group, ICH group and DFA treatment group. ICH model of rat basal ganglia was prepared by collagenase. DFA was injected intraperitoneally every 12 hours after operation for 7 days. The iron concentration in the brain tissue around the hematoma was measured at different time points after administration. OX42 immunohistochemistry was used to observe the changes of microglia in the brain tissue around the hematoma. The levels of IL-1β and TNF-α in brain tissue were measured by ELISA. Neurological deficit score and Nissl staining DFA treatment to observe the recovery of neurological function and neuronal loss. Results At the 3rd day after ICH, the concentration of Fe 2+ in the brain tissue around the hematoma was significantly higher than that in the sham-operated group and continued to 28 days, accompanied by a significant increase in the number of local microglia. After administration of DFA, the iron concentration in the brain tissue around the hematoma was significantly decreased, the number of microglia was significantly reduced, and the levels of neurotrophic cytokines IL-1β and TNF-α secreted by activated microglial cells were significantly decreased. At the same time, the loss of neurons in the perihematoma tissue was significantly reduced, and the neurological deficit score was significantly reduced. Conclusion ICH sustained release of iron ions can activate the local microglial cells, causing secondary brain injury. DFA improves secondary neurological dysfunction by clearing out iron ions in the brain tissue surrounding the hematoma, inhibiting microglial activation and reducing neuronal death in ICH.