微波辐射致大鼠海马损伤的磁共振影像学特征与其生物效应间关联性的研究
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摘要
目的通过对比性研究大鼠在微波辐射后的功能磁共振影像技术(fMRI)获取的海马影像表征参数与空间记忆能力及海马脑区病理结构改变之间的关联性,探讨将fMRI应用于微波辐射脑损伤效应研究的可行性。方法以30 mW/cm~2的微波一次辐射27只Wistar雄性大鼠15 min,对照组24只,于辐射后6 h、1 d、2 d、3 d、4 d、7 d、14 d分别采用Morris水迷宫检测大鼠空间记忆能力改变;光镜和电镜观察海马脑区病理变化;并应用fMRI的扩散加权成像(DWI)、动脉自旋标记(ASL)和磁共振波谱(MRS)等技术动态扫描海马脑区的表观扩散系数(ADC)、血流灌注(CBF)、代谢物质等变化。结果微波辐射后1~3 d大鼠平均逃避潜伏期(AEL)显著延长(P<0.05或P<0.01);海马神经元出现变性、凋亡(核染色质凝聚、边集)、坏死;线粒体肿胀空化、血管周间隙增宽。fMRI扫描成像显示,辐射后3~14 d分别海马脑区ADC值升高,血流灌注(CBF)减少,MRS显示海马脑区代谢物质N-乙酰天门冬氨酸与肌酸的比值(NAA/Cr)、谷氨酸类化合物与肌酸的比值(Glx/Cr)显著增加,胆碱化合物与肌酸的比值(Cho/Cr)显著降低,上述海马区病变及行为认知障碍等损伤效应与fMRI显示的特征参数在辐射后1~7 d呈现明显的一致性。结论微波辐射致大鼠海马损伤的fMRI特征与其行为认知障碍、组织结构病变及生物代谢指标变化具有良好的关联性。
Objective To explore the correlation between the functional magnetic resonance imaging(fMRI) characteristics and the spatial memory ability and the pathological changes of hippocampus in rats after exposured under microwave radiation. To discuss the feasibility of fMRI in studying the microwave radiation injury. Methods 27 rats were irradiated by 30 mW/cm~2 microwave for 15 min,after that the radiation group were used to test spatial memory in Morris water maze(MWM); hippocampus was observed pathological changes under optical microscope and transmission electron microscope; we chose DWI,ASL,MRS of fMRI scanning in the rats hippocampus to detect the changes of ADC,CBF and metabolic substances. Results 1 ~ 3 d after microwave exposure,the average escape latency(AEL) of rats was prolonged in MWM test. Degeneration and apoptosis(nuclear chromatin condensation and margination) and necrosis; mitochondria swelling and perivascular space widened can be observed in the hippocampus. 3 ~ 14 d after microwave exposure,fMRI imaging shows that ADC increased and CBF decreased; significant increases in NAA/Cr and Glx/Cr,but significant decreases in Cho/Cr in part of the hippocampus. A significant consistency between the pathological changes in hippocampus and cognitive impairment and the the changes of MRS especially in the 1 ~ 7 d. Conclusions It was found that the magnetic resonance imaging characteristics of hippocampus injury induced by microwave radiation were correlated with cognitive impairment,pathological changes of hippocampus and biological metabolism.
Objective To explore the correlation between the functional magnetic resonance imaging(fMRI) characteristics and the spatial memory ability and the pathological changes of hippocampus in rats after exposured under microwave radiation. To discuss the feasibility of fMRI in studying the microwave radiation injury. Methods 27 rats were irradiated by 30 mW/cm~2 microwave for 15 min,after that the radiation group were used to test spatial memory in Morris water maze(MWM); hippocampus was observed pathological changes under optical microscope and transmission electron microscope; we chose DWI,ASL,MRS of fMRI scanning in the rats hippocampus to detect the changes of ADC,CBF and metabolic substances. Results 1 ~ 3 d after microwave exposure,the average escape latency(AEL) of rats was prolonged in MWM test. Degeneration and apoptosis(nuclear chromatin condensation and margination) and necrosis; mitochondria swelling and perivascular space widened can be observed in the hippocampus. 3 ~ 14 d after microwave exposure,fMRI imaging shows that ADC increased and CBF decreased; significant increases in NAA/Cr and Glx/Cr,but significant decreases in Cho/Cr in part of the hippocampus. A significant consistency between the pathological changes in hippocampus and cognitive impairment and the the changes of MRS especially in the 1 ~ 7 d. Conclusions It was found that the magnetic resonance imaging characteristics of hippocampus injury induced by microwave radiation were correlated with cognitive impairment,pathological changes of hippocampus and biological metabolism.
引文
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[2]陈娟,王德文,左红艳,等.电磁辐射对海马损伤的病理及相关因子表达定量测定[J].解放军预防医学杂志,2007,25(2):82-86.Chen Juan,Wang Dewen,Zuo Hongyan,et al.Effects ofelectromagnetic radiations on the morphology in hippocampus and the expressison of injury-related proteins[J].Prev Med Chin PLA,2007,25(2):82-86.
[3]Wang H,Peng R,Zhou H,et al.Impairment of longterm potentiation induction is essential for the disruption of spatial memory after microwave exposure[J].Int J Radiat Biol,2013,89(12):1100-1107.
[4]马迪,彭瑞云,高亚兵,等.微波辐射对大鼠海马组织结构及其能量代谢的影响[J].中国体视学与图像分析,2010,(15)4:420-424.Ma Di,Peng Ruiyun,Gao Yabing,et al.Effects of microwave radiatio on structure and energy metabolism in rat hippocampus[J].Chinese Journal of Stereology and Image Analysis,2010,15(4):420-424.
[5]Magistretti P J,Allaman I.A cellular perspective on brain energy metabolism and functional imaging[J].Neuron,2015,86:883-901.
[6]Li H J,Hou X H,Liu H H,et al.Toward systems neuroscience in mild cognitive impairment and Alzheimer's disease:a meta-analysis of 75 f MRI studies[J].Hum Brain Mapp,2015,36:1217-1232.
[7]王德文,程天民.现代军事病理学[M].北京:军事医学科学出版社,2002:5-7,240-248,611-613.Wang Dewen,Cheng Tianming.Modern military pathology[M].Military Medical Science Press,2002:5-7,240-248,611-613.
[8]Zuo H,Lin T,Wang D,et al.Neural cell apoptosis induced by microwave exposure through mitochondriadependent caspase-3 pathway[J].Int J Med Sci,2014,11:426-435.
[9]Zhao L,Sun C,Xiong L,et al.MicroRNAs:novel mechanism involved in the pathogenesis of microwave exposure on rats'hippocampus[J].J Mol Neurosci,2014,53:222-230.
[10]Wang H,Peng R,Zhao L,et al.The relationship between NMDA receptors and microwave-induced learning and memory impairment:a long-term observation on Wistar rats[J].Int J Radiat Biol,2015,91:262-269.
[11]左红艳,王德文,陈娟,等.电磁辐射致海马损伤的比较蛋白质组学研究[J].中国体视学与图像分析,2006,11(4):263-268.Zuo Hongyan,Wang Dewen,Chen Juan,et al.Comparative proteome analysis of the hippocampus injured by electromagnetic radiation[J].Chinese Journal of Stereology and Image Analysis.2006,11(4):263-268.
[12]Zhao Y,Wu G,Shi H,et al.Relationship between cognitive impairment and apparent diffusion coefficient values from magnetic resonance-diffusion weighted imaging in elderly hypertensive patients[J].Clin Interv Aging,2014,28:1223-1231.
[13]Zimny A,Bladowska J,Neska M,et al.Quantitative MR evaluation of atrophy,as well as perfusion and diffusion alterations within hippocampi in patients with Alzheimer's disease and mild cognitive impairment[J].Med Sci Monit,2013,4:86-94.
[14]陈旭高,邹建勋,王明杰,等.3.0T磁共振ASL及MRS技术在阿尔茨海默病的应用研究[J].医学影像学杂志,2015,25:14-17.Chen Xugao,Zou Jjianxun,Wang Mingjie,et al.3.0T MRI arterial spin labeling and magnetic resonance spectroscopy technology in application of Alzheimer’s disease[J].J Med Imaging,2015,25:14-17.
[15]Jozefovicova M,Herynek V,Jiru F,et al.Minipig model of Huntington s disease:1H magnetic resonance spectroscopy of the brain[J].Physiol Res,2016,65:155-163.
[16]Tumati S I,Martens S,Aleman A.Magnetic resonance spectroscopy in mild cognitive impairment:systematic review and meta-analysis[J].Neurosci Biobehav,2013,37:2571-86.
[17]Peng W F,Ding J,Mao L Y,et al.Increased ratio of glutamate/glutamine to creatine in the right hippocampus contributes to depressive symptoms in patients with epilepsy[J].Epilepsy Behav,2013,29(1):144-149.