STZ诱导大鼠1型糖尿病进行性脑萎缩的磁共振成像及组织化学研究

STZ-Induced Progressive Brain Atrophy Studied by Magnetic Resonance Imaging and Histochemical Staining

1型糖尿病(T1DM)是一种慢性代谢疾病,主要表现为胰岛素分泌量较正常情况下降,会对人体的多个器官和系统造成持续性的损伤.关于糖尿病的横向研究发现糖尿病患者相比于正常人存在着显著的脑萎缩,但关于糖尿病引起的脑萎缩随时间发生进行性改变的研究比较少见.实验采用腹腔注射链脲佐菌素(STZ)来诱导建立大鼠的1型糖尿病模型,运用磁共振成像(MRI)的方法对萎缩的脑区进行定位并在造模后12周和20周两个时间点对脑萎缩的程度进行对比分析,然后运用组织化学染色的方法观察在MRI上出现进行性萎缩的脑区中的神经元所发生的病理改变.MRI的结果表明:STZ诱导的T1DM大鼠相比于正常对照组大鼠出现了显著性的全脑体积、灰质体积和白质体积的萎缩,并且在多个白质脑区和灰质脑区均出现了萎缩程度随着病程的延长而逐渐加重.组织化学染色的结果发现,STZ诱导的T1DM大鼠相对于正常对照组大鼠在体感皮层、运动皮层和海马CA3区,均出现明显的神经元萎缩现象.

Type 1 diabetes mellitus （T1DM） is a chronic metabolic disease characterized by insulin deficiency. Chronic T1DM causes damages to multiple organs. Numerous cross-sectional studies have shown that T1DM patients had significant cerebral atrophy, compared to normal subjects. However, few previous studies investigated progressive changes of cerebral atrophy over time in T1DM. In this study, a rat model of T1DM was established by a single dose of intraperitoneal injection of streptozotocin （STZ）. Magnetic resonance imaging （MRI） was employed to measure the volumetric changes of the brain at 12 weeks and 20 weeks after STZ induction to follow the progressive brain atrophy assessment between these two time points. Histochemical staining was used assess neuropathologic changes in the brain regions showing progressive atrophy. The MRI results demonstrated that the STZ-treated rats had significantly reduced volume of grey matter （GM）, white matter （WM） and whole brain, as compared to control. Voxel-wise analysis revealed significant effect of group＆#215;time interaction in multiple GM and WM regions. Results of Nissl staining and hematein-eosin staining （HE） indicate significant neuronal abnormality in the brain regions showing progressive atrophy, including somatosensory cortex, motor cortex and hippocampal CA3 region.