颐脑解郁方对抑郁大鼠脑1H波谱的干预作用

该文主要研究抑郁大鼠脑的¹H MRS变化及颐脑解郁方的干预作用. 将雄性Wistar大鼠随机分为正常组、模型组、西药组和中药组,每组5只. 正常组常规饲养,模型组、中药组和西药组给予21 d的慢性不可预知的温和应激. 应激结束中药组予颐脑解郁方、西药组予盐酸氟西汀进行干预. 干预结束后,通过检测左侧海马及前额叶皮质N-乙酰天门冬氨酸（NAA）、胆碱（Cho）、肌酸（Cr）等代谢物水平,分别计算NAA、Cho与Cr的比值,进而对脑组织代谢进行定性及定量分析. 得到：1. 海马区域：与正常组相比,模型组、西药组大鼠海马NAA/Cr降低（P<0.01）,中药组大鼠NAA/Cr与模型组相比升高（P<0.05）;与正常组相比,模型组Cho/Cr升高（P<0.05）,中药组Cho/Cr比模型组显著低（P<0.01）. 2. 前皮质区域：与正常组相比,模型组、西药组大鼠前皮质NAA/Cr降低（P<0.01）,中药组大鼠NAA/Cr较模型组显著升高（P<0.01）;模型组、西药组Cho/Cr与正常组相比显著升高（P<0.01）;与模型组相比,中药组、西药组Cho/Cr降低（P<0.01,P<0.05）. 这些结果说明颐脑解郁方可改善大鼠海马和前皮质的物质代谢,推测其抗抑郁作用主要与调节脑组织异常代谢有关.     

1H MRS评价长期胰岛素治疗1型糖尿病大鼠海马代谢物的变化

本研究应用质子磁共振波谱（¹H MRS）技术对链脲佐菌素（STZ）诱导的1型糖尿病（T1DM）大鼠及长期胰岛素治疗的T1DM大鼠单侧海马的代谢物进行了分析. 结果发现,与对照组大鼠及胰岛素治疗组大鼠相比,T1DM模型组大鼠空腹血糖显著升高,体重显著降低（p < 0.05）.T1DM模型组肌醇（Ins）、牛磺酸（Tau）与谷氨酸（Glu）浓度较对照组显著升高（p = 0.000、p = 0.003、p = 0.014）.胰岛素治疗组Ins与Tau浓度较T1DM模型组显著降低（p = 0.000、p = 0.010）,与对照组无差别;而Glu、谷氨酸和谷氨酰胺（Glx）浓度较对照组显著升高（p = 0.007、p = 0.042）.本文结果表明T1DM大鼠海马区代谢物Ins浓度与Tau浓度对胰岛素治疗敏感.     

电刺激诱发大鼠慢性颞叶癫痫模型的磁共振成像和波谱特征的研究

应用磁共振成像(MRI)和质子定域波谱(¹H-MRS)对强直流电刺激大鼠基树突区诱发慢性颞叶癫痫模型进行研究. MRI实验表明： 随着强直流电刺激时间的延长,在T₂加权像(T₂-MRI)中,模型大鼠的海马区腹、中侧区单侧或双侧,呈现异常高信号,扩散加权像(DWI)信号呈低信号,质子密度像无明显改变,表明T₂值和表观扩散系数(ADC) 值较大的自由水比例增大. 磁共振波谱实验发现：模型大鼠T₂-MRI中信号异常区与其对侧区的¹H-MRS相比,NAA,PCr（包括Cr）和Cho的峰面积均无显著改变,表明在慢性颞叶癫痫模型早期¹H-MRS不能检测到神经元损伤或死亡.     

大鼠脑缺血边缘区代谢物1H-MRS的研究

目的 利用不同的局灶性脑缺血模型，评价急性缺血后磁共振质子波谱（¹H-MRS）测定缺血后边缘区脑组织代谢和生物能量变化的时空规律. 为判定急性缺血预 后，进行有效的溶栓治疗提供有价值的生物化学信息. 方法 健康Sprague-Dawly大鼠9只，雌雄不拘，随机分为两组. A组（4只），自体血栓栓塞1 h；B组（5只），线栓法栓塞1 h. 分别 于栓塞后30、40、50、60 min进行¹HMRS检查，相对含量分析兴趣区（regio ns of interest, ROIs）氮-乙酰天门冬氨酸（NAA）、胆碱（Cho）和乳酸（Lac）等代谢产物的变化. 结果 以NAA、Cho、Lac与磷酸肌酸和肌酸（PCr+Cr）的谱峰积 分面积比值为判断标准，上述各代谢产物在兴趣区内于缺血后1 h内逐渐下降. 其中缺血后60 min，Cho/ （P Cr+Cr）、NAA/（PCr+Cr）及Lac/（PCr+Cr）的比值与缺血后50 min的比值统计学有显著性 差异（P<0.05）. 结论 ¹H-MRS技术为研究急性缺血性卒中后脑细胞代谢、生化能量状态提供了一个无创性、直接性、综合性的研究工具.     

1.5T磁共振化学交换饱和转移成像的影响因素分析

本文探讨1.5 T磁共振化学交换饱和转移(Chemical Exchange Saturation Transfer,CEST)成像的影响因素.通过试管模型和临床病例,采用GE Signa HDe 1.5 T磁共振成像(Magnetic Resonance Imaging,MRI)扫描仪分别进行不同矩阵、激励次数、翻转角、磁化传递翻转角的CEST成像对比分析,以及不同激励次数、磁化传递翻转角的Z谱分析,并从成像组织、成像设备、成像技术等方面对原始图信号、酰胺质子转移(Amide Proton Transfer,APT)信号及Z谱进行分析研究.实验结果表明1.5 T MRI扫描仪的CEST图像信噪比相对较低,且磁场稳定性及均匀度影响了CEST成像的效果.在其他参数不变的情况下,降低采集矩阵和增加激励次数与翻转角可以增加原始图像信噪比.磁化传递翻转角为105?时,CEST成像效果最好.激励次数为2、磁化传递翻转角为105?时,所得数据符合组织Z谱情况.模型Z谱在磁化传递频率为-294~-194 Hz范围可显示30%谷氨酸(Glu)、碘剂(I_(320))、纯水(H_2O)、肌酸(Cr)的信号差异,与H_2O差异最大处在-244~-214 Hz.原始图像信号30%I320明显高于Glu、H_2O、Cr,Cr略低于Glu,APT图Cr略低于Glu.25例脑肿瘤的APT图呈高信号、12例脑梗塞的APT图呈低信号,CEST原始图像均可区分病变区域.有12例因采集时间、患者配合情况、环境及室温等影响导致CEST成像的失败.由此得出1.5 T场强下,CEST技术受到成像组织、设备、技术等因素的影响,需要进行多方面优化.在保证磁场稳定性及均匀度的情况下,优化参数的CEST成像和Z谱成像可以区分代谢物及其浓度.     

HR-MAS NMR研究大鼠颞叶、海马和内嗅皮质的生理代谢表征

颞叶结构参与了多种中枢退行性疾病的发生和发展. 了解生理状态下大鼠的这些脑区的代谢特征可以为动物模型的病理研究提供基础数据和参考. 本文采用高分辨魔角旋转核磁共振（HR-MAS NMR）波谱技术和主成分分析（PCA）方法对S.D.大鼠双侧颞叶、海马和内嗅皮质的代谢物进行了分析，结果发现这3个脑区的代谢表征存在显著差异. 颞叶区的N-乙酰天门冬氨酸和牛磺酸的浓度最高，肌醇和肌酸的浓度最低；海马区的甘氨酸和胆碱的浓度最高；而在内嗅皮质区则是谷氨酰氨的浓度最高. 另外，还证实了HR-MAS NMR-PCA技术是研究生理和病理状态下脑组织各亚结构代谢表征的一种有效的手段.     

利用基于~1H NMR的代谢组学分析研究重离子辐射对大鼠额叶皮质区的影响

太空辐射尤其是重离子辐射可造成DNA的破坏、细胞死亡、以及一些癌症的发生, 是人类深空探索进程中急需克服的难题. 本文通过重离子加速器产生 ~(12)C~(6+)重离子束对大鼠头部进行一定剂量的辐射, 模拟空间重离子辐射对中枢神经系统(CNS)的生物学效应. 采用基于 ~1H NMR的代谢组学方法对辐射大鼠大脑额叶皮质区进行了测定分析, 结合数据的统计分析和检验, 发现了包括一些重要CNS神经递质在内的代谢物含量发生明显变化. 这些代谢物主要为: 牛磺酸、乳酸、谷氨酸、 4-氨基丁酸、以及磷酸胆碱等. 结合差异蛋白质组结果分析, 包括4-氨基丁酸、谷氨酸、乳酸、牛磺酸等在内的代谢物参与的主要生物途径, 如神经递质的合成途径, 以及神经递质受体介导的信号途径可能受重离子辐射的负面影响. 这些发现将为进一步阐明重离子辐射效应的分子机制提供有利信息, 从而为从生物学途径探寻有效重离子辐射防护措施提供依据.     

一种脑代谢研究的有效方法——高分辨率磁共振波谱分析

介绍了一种脑代谢研究的有效方法.成年大鼠脑经漏斗法液氮冷冻,制备脑组织高氯酸提取物并冷冻干燥,所得固体溶于D2O后用¹H和³¹P磁共振波谱(MRS)检测.结果表明：脑高氯酸提取物的磁共振波谱有着极好的分辨率,³¹P MRS可以分辨出ATP、ADP、磷酸肌酸(PCr)、无机磷以及多种磷酯和糖磷;¹H MRS可以分辨出乳酸(Lac)、N-乙酰天冬氨酸(NAA)、胆碱(Cho)、肌酸(Cr)、GABA、肌醇(Ino)、琥珀酸(Suc)以及多种氨基酸.各波峰积分后得到各种物质的相对含量,而这些代谢中间产物的相对含量变化可以反应脑内的代谢状况和脑受损伤情况.     

利用基于~1H NMR的代谢组学分析研究重离子辐射对大鼠额叶皮质区的影响

太空辐射尤其是重离子辐射可造成DNA的破坏、细胞死亡、以及一些癌症的发生,是人类深空探索进程中急需克服的难题. 本文通过重离子加速器产生¹²C⁶⁺重离子束对大鼠头部进行一定剂量的辐射,模拟空间重离子辐射对中枢神经系统(CNS)的生物学效应. 采用基于¹H NMR的代谢组学方法对辐射大鼠大脑额叶皮质区进行了测定分析,结合数据的统计分析和检验,发现了包括一些重要CNS神经递质在内的代谢物含量发生明显变化. 这些代谢物主要为：牛磺酸、乳酸、谷氨酸、4-氨基丁酸、以及磷酸胆碱等. 结合差异蛋白质组结果分析,包括4-氨基丁酸、谷氨酸、乳酸、牛磺酸等在内的代谢物参与的主要生物途径,如神经递质的合成途径,以及神经递质受体介导的信号途径可能受重离子辐射的负面影响. 这些发现将为进一步阐明重离子辐射效应的分子机制提供有利信息,从而为从生物学途径探寻有效重离子辐射防护措施提供依据.     

基于UHPLC-QE-MS的CCI模型大鼠的血清代谢组学研究

采用超高效液相色谱-四级杆静电场轨道阱质谱（UHPLC-QE-MS）非靶向代谢组学方法,观察CCI模型大鼠血清内源性代谢物的变化,筛选出慢性坐骨神经痛大鼠血清差异性代谢物,分析慢性疼痛对差异性代谢物的影响。将12只SPF级SD雄性大鼠随机均分为正常组和坐骨神经慢性压迫损伤（CCI）组,每组6只。CCI组建立大鼠左侧坐骨神经慢性压迫损伤模型,正常组除不结扎坐骨神经,其余步骤一样。14天后腹主动脉采血, 分离血清,对大鼠血清中的代谢物进行代谢组学检测。利用UHPLC-QE-MS技术并结合PCA(主成分分析)筛选差异代谢物,利用MetabolicAnalyst5.0进行差异代谢物的富集分析。富集分析结果表明,与正常对照组相比,CCI模型大鼠血清有机酸、有机杂环化合物、脂肪酰基、碳水化合物、核酸、有机氮化合物、碳氢化合物等9类代谢物具有统计学差异。结果表明：基于UHPLC-QE-MS的血清代谢组学方法能够有效区分正常组和CCI组,筛选出的差异代谢物有助于慢性疼痛的机制及药物靶点研究。     

Magnetic resonance spectroscopy study of proton metabolite level changes in sensorimotor cortex after upper limb replantation-revascularization

We aimed to investigate the changes in proton metabolite levels at the motor and somatosensory cortex by magnetic resonance spectroscopy (MRS) after upper extremity replantation or revascularization. Nine patients who referred to our clinic suffering from major total (two) and subtotal (seven) amputation of the upper extremity were enrolled in this study. Mean time value between the injury and operation was 5.1 h. Mean follow-up period or mean time between the injury and MRS analysis was 26.2 months (ranging from 7 to 41 months). Voxels (TR: 2000; TE: 136 ms) were placed onto locations in the bilateral precentral and postcentral cortex area of the cerebral hemispheres that represent the upper extremity. Contralateral sides of the brain hemisphere that represent the injured extremity were accounted as control groups. Metabolite ratios [NAA (N-acetyl aspartate)/Cr (creatine) and Cho (choline)/Cr] of the motor and somatosensory cortex were calculated. The NAA/Cr and Cho/Cr metabolite ratios between the two groups were found to be insignificant, and these results may indicate that there is no remarkable somatosensorial cortex disruption or demyelination in these patients. Fifty-six percent of patients were found as functional according to Chen's scale.     

Experimental hypoxic–ischemic encephalopathy: comparison of apparent diffusion coefficients and proton magnetic resonance spectroscopy

This study aims to compare the apparent diffusion coefficients (ADCs) and proton magnetic resonance spectroscopy (¹H-MRS) in the first 24 h of acute hypoxic-ischemic brain damage (HIBD) in piglets. Twenty-five 7-day-old piglets were subjected to transient bilateral common carotid artery occlusion followed by ventilation with 4% oxygen for 1 h. Diffusion-weighted imaging (DWI) and ¹H-MRS were performed on cessation of the insult or at 3, 6, 12 or 24 h after resuscitation (all n=5). ADCs, N-acetylaspartate/choline (NAA/Cho), NAA/creatine (NAA/Cr), lactate/NAA (Lac/NAA), Lac/Cho and Lac/Cr were calculated. Cerebral injury was evaluated by pathological study and Hsp70 immunohistochemical analysis. On cessation of the insult, ADCs, NAA/Cho and NAA/Cr reduced, Lac/NAA, Lac/Cho and Lac/Cr increased. From 3 to 12 h after resuscitation, ADCs, Lac/NAA, Lac/Cho and Lac/Cr recovered, NAA/Cho and NAA/Cr reduced. Twenty-four hours after resuscitation, ADCs reduced once more, Lac/NAA, Lac/Cho and Lac/Cr increased again, whereas NAA/Cho and NAA/Cr decreased continuously. Pathological study revealed mild cerebral edema on cessation of the insult and more and more severe cerebral injury after resuscitation. No Hsp70-positive cells were detected on cessation of the insult. From 3 to 12 hours after resuscitation, Hsp70-positive cells gradually increased. Twenty-four hours after resuscitation, Hsp70-positive cells decreased. Throughout the experiment, changes in NAA/Cho and pathology had the best correlation (R=–0.729). In conclusion, NAA/Cho is the most precise ratio to reflect the pathological changes of early HIBD. Transient ADCs and Lac ratios recovery do not predict the reversal of histological damage of early HIBD. Reducing astrocytic swelling is of great clinical significance.     

High-field localized 1H NMR spectroscopy in the anesthetized and in the awake monkey

Localized cerebral in vivo ¹H NMR spectroscopy (MRS) was performed in the anesthetized as well as the awake monkey using a novel vertical 7 T/60 cm MR system. The increased sensitivity and spectral dispersion gained at high field enabled the quantification of up to 16 metabolites in 0.1- to 1-ml volumes. Quantification was accomplished by using simulations of 18 metabolite spectra and a macromolecule (MM) background spectrum consisting of 12 components. Major cerebral metabolites (concentrations >3 mM) such as glutamate (Glu), N-acetylaspartate (NAA), creatine (Cr)/phosphocreatine (PCr) and myo-inositol (Ins) were identified with an error below 3%; most other metabolites were quantified with errors in the order of 10%. Metabolite ratios were 1.39:1 for total NAA, 1.38:1 for glutamate (Glu)/glutamine (Gln) and 0.09:1 for cholines (Cho) relative to total Cr. Taurine (Tau) was detectable at concentrations lower than 1 mM, while lactate (Lac) remained below the detection limit. The spectral dispersion was sufficient to separate metabolites of similar spectral patterns, such as Gln and Glu, N-acetylaspartylglutamate (NAAG) and NAA, and PCr–Cr. MRS in the awake monkey required the development and refinement of acquisition and correction strategies to minimize magnetic susceptibility artifacts induced by respiration and movement of the mouth or body. Periods with major motion artifacts were rejected, while a frequency/phase correction was performed on the remaining single spectra before averaging. In resting periods, both spectral amplitude and line width, that is, the voxel shim, were unaffected permitting reliable measurements. The corrected spectra obtained from the awake monkey afforded the reliable detection of 6–10 cerebral metabolites of 1-ml volumes.     

Brain abscess observed by localized proton magnetic resonance spectroscopy

We encountered a case of brain abscess that was difficult to differentiate from glioblastoma. Localized ¹H-MRS was found to be useful for obtaining information on the biochemical status of brain abscess. The peak of lipid and high residual peak of NAA (N-acetyl-aspartate) were observed in the cystic lesion of the brain abscess by ¹H-MRS. The NAA/Cho (Choline-containing compounds) ratio in brain parenchyma showing an edematous lesion before therapy gradually increased with the relief of inflammation.     

Spectroscopic imaging of radiation-induced effects in the white matter of glioma patients

External radiation therapy of brain tumors may cause adverse effects on normal brain tissue, resulting in severe neuropsychological and cognitive impairment. We investigated the late delayed radiation effects in the white matter (WM) using (1)H magnetic resonance spectroscopic imaging ((1)HMRSI). Nine glioma patients with local radiation-induced signal abnormalities in the T(2)-weighted MR images were studied with nine age- and sex-matched controls. The metabolite ratios in the radiation-induced hyper intensity area (RIHA) and in the normal appearing white matter (NAWM) of the patients were compared with respective WM areas of the controls. In RIHA, choline/creatine (Cho/Cr) was 17% decreased (1.22 +/- 0.13 vs 1.47 +/- 0.16, p = 0.0027, significant (s), unpaired Student's t test with Bonferroni correction) in the patients compared to the controls, while there was no difference in N-acetyl aspartate/Cr (NAA/Cr) (2.49 +/- 0.57 vs 2.98 +/- 0.32, p = 0.039) or NAA/Cho (2. 03 +/- 0.40 vs 2.04 +/- 0.17, p = 0.95). In NAWM, Cho/Cr was 24% decreased (1.21 +/- 0.15 vs 1.59 +/- 0.13, p < 0.0001, s) and NAA/Cho was 20% increased (2.49 +/- 0.49 vs 1.98 +/- 0.15, p = 0. 0082, s) in the patients compared to the controls, while there was no difference in NAA/Cr (2.99 +/- 0.46 vs 3.16 +/- 0.32, p = 0.38). NAA(RIHA)/NAA(NAWM) was 25% decreased (0.75 +/- 0.20 vs 1.00 +/- 0. 12, p = 0.0043, s) and Cr(RIHA)/Cr(NAWM) was 16% decreased (0.89 +/- 0.15 vs 1.06 +/- 0.10, p = 0.013, s) in the patients compared to the controls, while there was no difference in Cho(RIHA)/Cho(NAWM) (0.92 +/- 0.23 vs 0.98 +/- 0.10, p = 0.47). (1)HMRSI reveals widespread chemical changes in the WM after radiation therapy. In RIHA, there is loss of NAA, Cho, and Cr implying axonal and membrane damage and in NAWM, there is loss of Cho, reflecting membrane damage.     

Proton MR spectroscopy of cerebellitis

Single voxel proton MR spectroscopy ((1)H-MRS) of the vermis was obtained in two patients with cerebellitis. In the acute phase (1)H-MRS revealed low N-acetyl-aspartate (NAA)/creatine (Cr) and NAA/choline (Cho) and normal Cho/Cr ratios. Decrease of the concentration of NAA was confirmed by quantitative analysis in one patient. The NAA/Cr and NAA/Cho ratios and NAA concentration were increased in (1)H-MRS examinations obtained 10 and 24 months after the acute episode. (1)H-MRS demonstrates reversible metabolite changes in cerebellitis.     

Reversal of myo-inositol metabolic level in the left dorsolateral prefrontal cortex of rats exposed to forced swimming test following desipramine treatment: an in vivo localized H-MRS study at 4.7 T

The forced swimming test (FST) is a useful paradigm that is relatively quick and simple to perform and has been utilized to predict antidepressant activity based on learned helplessness as a model of depression. To date, few studies have used proton magnetic resonance spectroscopy (¹H-MRS) to assess antidepressant effects in rats. The purpose of this study was to assess desipramine (DMI) effects on the left dorsolateral prefrontal cortex (DLPFC) of the rats, which were randomly assigned to three groups (control, n=10; FST+saline, n=10; FST+DMI, n=10), using single-voxel localization technique. All ¹H-MRS experiments were performed on a Bruker 4.7-T scanner with 400 mm bore magnet, allowing for acquisition of in vivo ¹H point-resolved spectroscopy spectra (TR/TE=3000/30 ms, number of data points=2048, NEX=512, voxel volume=27 μl, scan time=25 min). Proton metabolites were quantified automatically using LCModel software and were expressed as ratios to total creatine (Cr+PCr). Major target metabolites such as N-acetyl aspartate (NAA)+N-acetylaspartylglutamate (NAAG), glutamate+glutamine (Glu+Gln), glycerophosphorylcholine+phosphorylcholine (GPC+PCho), myo-inositol (mIns) and taurine (Tau) were successfully quantified with Cramer–Rao lower boundary ≤10%. There were significantly higher mIns/(Cr+PCr) and mIns/(NAA+NAAG) ratios in the FST+saline group compared to the control group. In the FST+DMI group, both mIns/(Cr+PCr) and mIns/(NAA+NAAG) ratios were significantly decreased to the level similar to those in the control group. No other metabolite ratios were significantly different among the three groups. Our findings suggest a possible role of altered mIns level within the left DLPFC of the rat model for depression.