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

doi:10.11938/cjmr20150305

波谱学杂志 ›› 2015, Vol. 32 ›› Issue (3): 439-449.doi: 10.11938/cjmr20150305

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

黄微^1,2*，曹子玉^1,2

1. 中国科学院生物磁共振分析重点实验室，波谱与原子分子物理国家重点实验室，武汉磁共振中心（中国科学院武汉物理与数学研究所），湖北武汉 430071； 2. 中国科学院大学，北京 100049

收稿日期:2014-05-26 修回日期:2015-07-29 出版日期:2015-09-05 发布日期:2015-09-05
作者简介:黄微(1987-)，男，湖北武汉人，硕士研究生，分析化学专业．电话：13437162722, E-mail: huangweiwhu@163.com.

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

HUANG Wei^1,2*，CAO Zi-yu^1,2

1. Key Laboratory of Magnetic Resonance in Biological Systems, National Center for Magnetic Resonance in Wuhan, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics (Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences), Wuhan 430071, China; 2. University of Chinese Academy of Sciences, Beijing 100049, China

Received:2014-05-26 Revised:2015-07-29 Online:2015-09-05 Published:2015-09-05
About author:*Corresponding author：HUANG Wei, Tel: +86-13437162722, E-mail: huangweiwhu@163.com.

摘要/Abstract

摘要：

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．

关键词: 磁共振成像(MRI), 1型糖尿病(T1DM), 链脲佐菌素, 组织化学染色, 进行性脑萎缩

Abstract:

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×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.

Key words: MRI, type 1 diabetes, streptozotocin, histochemical staining, progressive brain atrophy

中图分类号:

O482.53

黄微1,2*，曹子玉1,2. 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[J]. 波谱学杂志, 2015, 32(3): 439-449.

HUANG Wei1,2*，CAO Zi-yu1,2. STZ-Induced Progressive Brain Atrophy Studied by Magnetic Resonance Imaging and Histochemical Staining[J]. Chinese Journal of Magnetic Resonance, 2015, 32(3): 439-449.

参考文献

[1] Alberti K, Zimmet P, Shaw J. A consensus statement from the International Diabetes Federation[J]. Diabet Med, 2010, 23(5): 469－480.

[2] Brownlee M. Biochemistry and molecular cell biology of diabetic complications[J]. Nature, 2001, 414(6 865): 813－820.

[3] Reske-Nielsen E, Lundbaek K. Pathological changes in the central and peripheral nervous system of young long-term diabetics. II. The spinal cord and peripheral nerves[J]. Diabetologia, 1968, 4(1): 34－43.

[4] Di Marzio D, Mohn A, Mokini Z H, et al. Macroangiopathy in adults and children with diabetes: from molecular mechanisms to vascular damage (part 1)[J]. Horm Metab Res, 2006, 38(11): 691－705.

[5] Folli F, Guzzi V, Perego L, et al. Proteomics reveals novel oxidative and glycolytic mechanisms in type 1 diabetic patients’ skin which are normalized by kidney-pancreas transplantation[J]. PLoS One, 2010, 5(3): e9923.

[6] Rask-Madsen C, King G L. Mechanisms of disease: endothelial dysfunction in insulin resistance and diabetes[J]. Nat Clin Pract Endocrinol Metab, 2007, 3(1): 46－56.

[7] Vlassara H, Brownlee M, Cerami A. Excessive nonenzymatic glycosylation of peripheral and central nervous system myelin components in diabetic rats[J]. Diabetes, 1983, 32(7): 670－674.

[8] Auer R N, Siesjö B K. Biological differences between ischemia, hypoglycemia, and epilepsy[J]. Ann Neurol, 1988, 24(6): 699－707.

[9] Auer R N, Olsson Y, Siesjö B K. Hypoglycemic brain injury in the rat. Correlation of density of brain damage with the EEG isoelectric time: a quantitative study[J]. Diabetes, 1984, 33(11): 1 090－1 098.

[10] Auer R N, Hugh J, Cosgrove E, et al. Neuropathologic ?ndings in three cases of profound hypoglycemia[J]. Clin Neuropathol, 1989, 8(2): 63－68.

[11] Fujioka M, Okuchi K, Hiramatsu K I, et al. Speci?c changes in human brain after hypoglycemic injury[J]. Stroke, 1997, 28(3): 584－587.

[12] Kalimo H, Olsson Y. Effects of severe hypoglycemia on the human brain. Neuropathological case reports[J]. Acta Neurol Scand, 1980, 62(6): 345－356.

[13] Sieber F E, Traystman R J. Special issues: glucose and the brain[J]. Crit Care Med, 1992, 20(1): 104－114.

[14] McCall A L. The impact of diabetes on the CNS[J]. Diabetes, 1992, 41(5): 557－570.

[15] Wieloch T. Hypoglycemia-induced neuronal damage prevented by an N-methyl-D-aspartate antagonist[J]. Science, 1985, 230(4 726): 681－683.

[16] Ouyang Y B, He Q P, Li P A, et al. Is neuronal injury caused by hypoglycemic coma of the necrotic or apoptotic type[J]. Neurochem Res, 2000, 25(5): 661－667.

[17] Xu Wen-xin(徐雯欣), An Yan-peng(安艳捧), Tang Hui-ru(唐慧儒). NMR studies of Streptozotocin effects on rat plasma fatty acids(链脲佐菌素影响大鼠脂肪酸代谢的NMR研究)[J]. Chinese J Magn Reson(波谱学杂志) , 2013, 30(2): 204－212.

[18] Huang Ming-ming(黄明明), Lin Fu-chun(林富春), Gao Li-feng(高丽凤), et al. Diabetic encephalopathy studied by magnetic resonance imaging and spectroscopy(糖尿病脑病的磁共振研究)[J]. Chinese J Magn Reson(波谱学杂志) , 2012, 29(3): 446－456.

[19] Tiehuis A M, van der Graaf Y, Visseren F L, et al. Diabetes increases atrophy and vascular lesions on brain MRI in patients with symptomatic arterial disease[J]. Stroke, 2008, 39(5): 1 600－1 603.

[20] Ferguson S C, Blane A, Wardlaw J, et al. Influence of an early-onset age of type 1 diabetes on cerebral structure and cognitive function[J]. Diabetes Care, 2005, 28(6): 1 431－1 437.

[21] Pell G S, Lin A, Wellard R M, et al. Age-related loss of brain volume and T₂ relaxation time in youth with type 1 diabetes[J]. Diabetes Care, 2012, 35(3): 513－519.

[22] Brands A M, Kessels R P, Hoogma R P, et al. Cognitive performance, psychological well-being, and brain magnetic resonance imaging in older patients with type 1 diabetes[J]. Diabetes, 2006, 55(6): 1 800－1 806.

[23] Falvey C M, Rosano C, Simonsick E M, et al. Macro- and micro-structural magnetic resonance imaging indices associated with diabetes among community-dwelling older adults[J]. Diabetes Care, 2013, 36(3): 677－682.

[24] Musen G, Lyoo I K, Sparks C R, et al. Effects of type 1 diabetes on gray matter density as measured by voxel-based morphometry[J]. Diabetes, 2006, 55(2): 326－333.

[25] Schweinhardt P, Bushnell M C. Pain imaging in health and disease—how far have we come[J]. J Clin Invest, 2010, 120(11): 3 788－3 797.

[26] Scoville W B, Milner B. Loss of recent memory after bilateral hippocampal lesion[J]. J Neurol Neurosurg Psychiatry, 1957, 20(1): 11－21.

[27] Zola-Morgan S M, Sguire L R. The primate hippocampal formation: evidence for a time-limited role in memory storage[J]. Science, 1990, 250(4 978): 288－290.

[28] Gaudieri P A, Chen R, Greer T F, et al. Cognitive function in children with type 1 diabetes: a meta-analysis[J]. Diabetes Care, 2008, 31(9): 1 892－1 897.

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

PDF

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价

[1]	魏国境, 易佩伟, 陶泉, 冯衍秋. CEST成像不同量化方式在急性帕金森氏病小鼠模型研究中的应用比较[J]. 波谱学杂志, 2019, 36(2): 195-207.
[2]	黄朝晖, 张志, 陈黎, 陈俊飞, 张震, 陈方, 刘朝阳. MRI梯度预加重模块的分时复用设计[J]. 波谱学杂志, 2018, 35(4): 465-474.
[3]	刘颖, 宋明辉, 王坤, 章浩伟. 基于全可编程SoC和LabVIEW的磁共振接收系统设计[J]. 波谱学杂志, 2018, 35(4): 475-485.
[4]	汪红志, 赵地, 杨丽琴, 夏天, 周皛月, 苗志英. 基于AI+MRI的影像诊断的样本增广与批量标注方法[J]. 波谱学杂志, 2018, 35(4): 447-456.
[5]	陈海燕, 赵世龙, 李晓南, 刘国强, 胡丽丽, 刘弢. 低场永磁体磁共振射频场映像[J]. 波谱学杂志, 2018, 35(4): 498-504.
[6]	陶泉, 易佩伟, 魏国境, 冯衍秋. 基于CEST机制的pH成像方法、原理和应用[J]. 波谱学杂志, 2018, 35(4): 505-519.
[7]	翟国强, 张苗, 薄斌仕, 王乙, 范明霞, 李建奇. 基于复值和模值的肝脏磁共振水脂分离组合算法[J]. 波谱学杂志, 2018, 35(4): 417-426.
[8]	孙炜航, 孙钰, 汪丰, 王超洪, 杨涛. 变延迟进动定制激发(DANTE)序列在工程中的优化设计[J]. 波谱学杂志, 2018, 35(2): 150-161.
[9]	崔妍, 肖亮. 磁共振成像谱仪B₀信号的高精度发生与测试[J]. 波谱学杂志, 2018, 35(2): 170-177.
[10]	张波, 谢海滨, 严序, 李文静, 杨光. 旋转不变的非局域均值算法在磁共振图像去噪中的应用[J]. 波谱学杂志, 2018, 35(2): 162-169.
[11]	马芸, 郭虹, 王秋实, 张伟国, 吴昊. 基于影像的形态学特征与胶质母细胞瘤特征分子表达的相关性研究[J]. 波谱学杂志, 2018, 35(1): 22-30.
[12]	黄丽洁, 宋阳, 赵献策, 谢海滨, 吴东梅, 杨光. 一种结合并行成像和压缩感知的快速磁共振成像新方法[J]. 波谱学杂志, 2018, 35(1): 31-39.
[13]	罗庆, 张成秀, 李文静, 郑慧, 谢海滨, 杨光. 一种新的磁共振图像处理流水线的设计与实现[J]. 波谱学杂志, 2018, 35(1): 40-51.
[14]	宋瑞, 何砚发, 张波. 一种永磁磁共振中磁体涡流场的测量方法[J]. 波谱学杂志, 2018, 35(1): 52-59.
[15]	李宇宙, 张喆, 陈泉荣, 郭华. 一种以超分辨率理论为基础的磁共振眼球成像方法[J]. 波谱学杂志, 2017, 34(4): 439-452.