Miao Xingyu, Liu Xiaobin, Yue Qing, Qiu Nan, Huang Weidong, Wang Jijun, Xu Yangang, Zhang Yuelin, Yang Jun, Chen Xinlin
Department of Neurosurgery, Shaanxi Provincial People's Hospital, Xi'an 710068, China.
Nan Fang Yi Ke Da Xue Xue Bao. 2012 Jun;32(7):970-5.
To investigate the effect of the iron chelator deferoxamine (DFA) in suppressing microglia activation and protecting against secondary neural injury in a rat model of intracerebral hemorrhage (ICH).
SD rats were randomly divided into sham-operated group, ICH group and DFA treatment group. ICH model was established by infusion of type IV collagenase into the right basal ganglia, and starting from 1 h after the operation, the rats received intraperitoneal DFA injections every 12 h for 7 days. The iron content in the perihematoma brain tissue was determined at different time points after DFA administration, and OX42 immunohistochemistry was used to observe the changes in the microglia. The contents of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in the brain tissue were detected by ELISA. The neural death and neurological deficiency were measured using Nissl staining and neurological scores, respectively.
The iron content in the brain tissues around the hematoma was significantly increased 3 days after ICH and maintained a high level till 28 days, accompanied by a marked increase of microglial cells as compared to the sham-operated group. DFA injection caused significantly decreased iron content in the brain tissue, reduced number of microglial cells, and lowered levels of IL-1β and TNF-α. Neuronal loss around the hematoma was obviously reversed after DFA injections, which resulted in improved neurological deficiency.
DFA can suppress microglia activation by removing iron overload from the perihematoma brain tissue, thus reducing secondary neuronal death and neurological deficiency in rats with ICH.
探讨铁螯合剂去铁胺（DFA）对脑出血（ICH）大鼠模型中小胶质细胞激活的抑制作用及对继发性神经损伤的保护作用。
将SD大鼠随机分为假手术组、ICH组和DFA治疗组。通过向右侧基底节注入IV型胶原酶建立ICH模型，术后1小时开始，大鼠每12小时腹腔注射DFA，共7天。在给予DFA后的不同时间点测定血肿周围脑组织中的铁含量，采用OX42免疫组织化学法观察小胶质细胞的变化。采用酶联免疫吸附测定法（ELISA）检测脑组织中白细胞介素-1β（IL-1β）和肿瘤坏死因子-α（TNF-α）的含量。分别采用尼氏染色和神经功能评分法测量神经细胞死亡和神经功能缺损情况。
ICH后3天血肿周围脑组织中的铁含量显著增加，并持续维持在较高水平直至28天，与假手术组相比，小胶质细胞数量明显增加。注射DFA可使脑组织中铁含量显著降低，小胶质细胞数量减少，IL-1β和TNF-α水平降低。注射DFA后血肿周围神经元丢失明显得到改善，神经功能缺损情况得到改善。
DFA可通过清除血肿周围脑组织中的铁过载来抑制小胶质细胞激活，从而减少ICH大鼠的继发性神经元死亡和神经功能缺损。
