Deferoxamine suppresses neuronal damage in T1DM rats by reducing cerebral iron content

CI Yunzhe; LI Haiyan; BAI Xuedong; MA Wenyi

doi:10.16016/j.2097-0927.202504070

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Deferoxamine suppresses neuronal damage in T1DM rats by reducing cerebral iron content

Neuroscience | 更新时间：2025-12-25

- Deferoxamine suppresses neuronal damage in T1DM rats by reducing cerebral iron content
- Journal of Army Medical University Vol. 47, Issue 20, Pages: 2558-2568(2025)
- 作者机构：
  
  1.承德医学院：组织学与胚胎学教研室，河北承德
  3.承德医学院：人体解剖学教研室，河北承德
  4.承德医学院：附属医院医学影像科，河北承德
  2.中国医科大学组织学与胚胎学教研室，辽宁沈阳
- 作者简介：
- 基金信息：
  
  the Youth Fund of Hebei Provincial Department of Education(QN2020229);the Project of Advantageous Disciplines in Human Anatomy and Histology and Embryology of Chengde Medical College;the Medical Scientific Research Project of Hebei Province(20200178)
- DOI：10.16016/j.2097-0927.202504070
  CLC： R587.1;R749.25;R979.3
- Received：17 April 2025，
  
  Revised：2025-09-19，
  
  Accepted：22 September 2025，
  
  Published：30 October 2025
- 稿件说明：
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次云哲，李海艳，白雪冬，等.去铁胺通过降低脑铁含量抑制T1DM大鼠神经元损伤［J］.陆军军医大学学报，2025，47（20）：2558-2568.DOI：10.16016/j.2097-0927.202504070.

CI Y Z，LI H Y，BAI X D，et al.Deferoxamine suppresses neuronal damage in T1DM rats by reducing cerebral iron content［J］.J Army Med Univ，2025，47（20）：2558-2568.DOI：10.16016/j.2097-0927.202504070.
次云哲，李海艳，白雪冬，等.去铁胺通过降低脑铁含量抑制T1DM大鼠神经元损伤［J］.陆军军医大学学报，2025，47（20）：2558-2568.DOI：10.16016/j.2097-0927.202504070. DOI：

CI Y Z，LI H Y，BAI X D，et al.Deferoxamine suppresses neuronal damage in T1DM rats by reducing cerebral iron content［J］.J Army Med Univ，2025，47（20）：2558-2568.DOI：10.16016/j.2097-0927.202504070. DOI：

摘要

目的

探讨去铁胺（deferoxamine，DFO）对1型糖尿病（type 1 diabetes mellitus，T1DM）模型大鼠认知功能障碍的改善作用，并阐明T1DM大鼠脑铁过载的分子机制。

方法

将36只健康雄性SD大鼠（体质量180~250 g）用计算机生成随机序列分为3组，每组12只：第1组为空白对照组（Ctrl），不作处理；第2组与第3组通过一次性腹腔注射65 mg/kg链脲佐菌素（Streptozotocin， STZ）建立T1DM大鼠模型，3 d后筛选空腹血糖≥16.7 mmol/L者纳入实验，其中第2组为糖尿病组（T1DM），第3组在STZ注射21 d后予以侧脑室注射DFO（5 μg/kg·d），连续给药28 d，设为DFO治疗组（DFO）。采用Morris水迷宫实验评估大鼠空间学习记忆能力；尼氏染色与免疫荧光染色观察海马及皮层神经元形态与数量变化；ICP-MS法检测海马组织铁含量；Western blot检测脑铁代谢相关蛋白的表达。

结果

Morris水迷宫显示T1DM组大鼠学习记忆能力显著下降（

0.01）；尼氏染色与免疫荧光染色表明T1DM大鼠神经元形态损伤，海马CA1区（

0.01）、CA3区（

0.01）及皮层（

0.05）神经元数量减少；ICP-MS检测提示T1DM组海马铁含量明显升高（

0.01）

；Western blot结果显示，T1DM组海马铁储存蛋白FTH（

0.01）和FTL（

0.05）及皮层FTH（

0.05）和FTL（

0.01）表达显著上调；海马与皮层中铁摄取蛋白DMT1表达均升高（

0.05）；海马铁输出蛋白FPN1（

0.01）及皮层FPN1（

0.05）表达下降；DFO干预后上述异常表现均得到显著改善。

结论

T1DM大鼠学习记忆能力下降与脑铁过载所致的神经元损伤密切相关；铁摄取蛋白DMT1与铁输出蛋白FPN1共同参与影响T1DM大鼠脑铁含量；DFO可通过调控DMT1与FPN1的表达，降低T1DM大鼠脑铁含量，从而减轻脑铁过载介导的神经元损伤。

Abstract

Objective

To investigate the ameliorative effect of deferoxamine (DFO) on cognitive impairment in a rat model of type 1 diabetes mellitus (T1DM) and to elucidate the molecular mechanisms underlying cerebral iron overload in T1DM rats.

Methods

Thirty-six healthy male SD rats (weighing 180~250 g) were randomly assigned into a blank control group (Ctrl)

a T1DM model group and a DFO group

with 12 rats in each group. A single dose of 65 mg/kg streptozotocin (STZ) was intraperitoneally injected to the rats to establish a T1DM model

and those with fasting blood glucose ≥16.7 mmol/L at 3 d later were designated as the T1DM group. Intracerebroventricular administration of DFO (5 μg/kg·d) was given to the DFO group for 28 consecutive days since 21 d after STZ injection. Morris water maze test was carried out to assess the spatial learning and memory abilities. Nissl staining and immunofluorescence assay were applied to observe neuronal morphology and number in the hippocampus and cortex. The iron content in the hippocampus was measured with inductively coupled plasma mass spectrometry (ICP-MS). The expression levels of iron metabolism related proteins were detected with Western blotting.

Results

In the T1DM group

significant declines in learning and memory abilities (

0.01) and impaired neuronal morphology and reduced neuronal counts in the hippocampal CA1 region (

0.01)

CA3 region (

0.01)

and cortex (

0.05) were observed when compared with those in the Ctrl group. ICP-MS analysis showed a marked increase in the hippocampal iron content in the T1DM group (

0.01). Western blot results demonstrated that T1DM rats exhibited obviously up-regulated expression of iron storage proteins FTH and FTL in both the hippocampus (

0.01

0.05) and the cortex (

0.05

0.01)

enhanced expression of iron import protein DMT1 in both the hippocampus and the cortex (

0.05)

while decreased expression of iron export protein FPN1 in the hippocampus (

0.01) and the cortex (

0.05). DFO treatment significantly ameliorated all above abnormalities.

Conclusion

The declines in learning and memory in T1DM rats are closely associated with neuronal damage induced by cerebral iron overload. Iron import protein DMT1 and export protein FPN1 jointly regulate cerebral iron content in T1DM rats. DFO reduces brain iron levels and mitigates iron overload-mediated neuronal injury by modulating the expression of DMT1 and FPN1.

关键词

Keywords

references

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