7.0T nuclear magnetic resonance evaluation of the amyloid beta(1–40) animal model of Alzheimer's disease: comparison of cytology verification

3.0T magnetic resonance spectroscopic imaging brain function in Alzheimer＇s disease. However, is a commonly used method in the research ot the role of 7.0T high-field magnetic resonance spectroscopic imaging in brain function of Alzheimer＇s disease remains unclear. In this study, 7.0T magnetic resonance spectroscopy showed that in the hippocampus of Alzheimer＇s disease rats, the N-acetylaspartate wave crest was reduced, and the creatine and choline wave crest was elevated. This finding was further supported by hematoxylin-eosin staining, which showed a loss of hippocampal neurons and more glial cells. Moreover, electron microscopy showed neuronal shrinkage and mitochondrial rupture, and scanning electron microscopy revealed small size hippocampal synaptic vesicles, incomplete synaptic structure, and reduced number. Overall, the results revealed that 7.0T high-field nuclear magnetic resonance spectroscopy detected the lesions and functional changes in hippocampal neurons of Alzheimer＇s disease rats in vivo, allowing the possibility for assessing the success rate and grading of the amyloid beta （1-40） animal model of Alzheimer＇s disease.

Investigation of formation of dimeric G-quadruplex of HIV-1 integrase inhibitor by nuclear magnetic resonance

In this research, an unusually dimeric G-quadruplex of d（GGGTGGGTGGGTGGGT） （SI）, the potent nanomolar HIV-1 integrase inhibitor, was detected by nuclear magnetic resonance （NMR）. This result has been confirmed by electrospray ionization mass spectrometry （ESI-MS） and circular dichroism （CD）.

Three dimensional structure prediction and proton nuclear magnetic resonance analysis of toxic pesticides in human blood plasma

The purpose of this study was to investigate the nuclear magnetic resonance （NMR） assignments of hydrolyzed products extracted from human blood plasma. The correlations between chemical, functional and structural prop- erties of highly toxic pesticides were investigated using the PreADME analysis. We observed that toxic pesticides possessed higher molecular weight and, more hydrogen bond donors and acceptors when compared with less toxic pesticides. The occurrence of functional groups and structural properties was analyzed using ~H-NMR. The ~H- NMR spectra of the phosphomethoxy class of pesticides were characterized by methyl resonances at 3.7-3.9 ppm （8） with the coupling constants of 11-16 Hz （Je-cns）. In phosphoethoxy pesticides, the methyl resonance was about 1.4 ppm （8） with the coupling constant of 10 Hz （Je-cH2） and the methylene resonances was 4.2-4.4 ppm （8） with the coupling constant of 0.8 Hz （Jp-cH3）, respectively. Our study shows that the values of four parameters such as chemical shift, coupling constant, integration and relaxation time correlated with the concentration of toxic pesticides, and can be used to characterise the proton groups in the molecular structures of toxic pesticides.

利用^(1)H NMR测定姜中姜辣素与姜黄素

该研究采用核磁共振氢谱(proton nuclear magnetic resonance,^(1)H NMR)技术对冻干生姜与烘干生姜中的姜辣素和姜黄素类化合物的变化进行定性定量分析,发现姜中姜辣素提取物主要包括6-姜酚、8-姜酚、10-姜酚等姜酚类物质以及少量姜烯酚。经过烘干处理后,总姜酚的含量由(1.5±0.3)mg/g降低至(0.89±0.06)mg/g(鲜重),总姜辣素的含量由(2.3±0.4)mg/g降低至(1.4±0.1)mg/g,6-姜烯酚的含量由(4.8×10^(-3)±2.7×10^(-3))mg/g升高至(0.0209±0.0004)mg/g。烘干后姜黄素类化合物的含量由(4.4±0.2)mg/100 g降低至(1.5±0.6)mg/100 g,香草醛的含量由(1.20±0.07)mg/100 g升高至(1.87±0.01)mg/100 g,说明热处理会导致生姜中的姜辣素与姜黄素类化合物降解,姜酚类物质向姜烯酚转化。该试验结果为研究姜中姜辣素与姜黄素类化合物的变化机理以及姜制品的生产与工艺优化提供了参考。

核磁共振氢谱法（~1H-NMR）测定西他沙星标准物质的含量

目的建立核磁共振氢谱法测定西他沙星标准物质的绝对含量。方法采用Bruker AVANCE-500型和AVANCE-300型仪器,分别以盐酸吉西他滨和齐多夫定为内标,西他沙星中质子信号在δ8.69,δ7.76,δ3.43和δ3.14,盐酸吉西他滨质子信号在δ8.12,δ6.21和δ6.02,齐多夫定中质子信号在δ7.61和δ6.01作为定量峰,0.5 mL DMSO-d6∶氚代盐酸（DCl,44.8mg·L^-1）=4∶1为溶剂,测定条件为：探头温度303K,谱宽11.0,中心频率4.9,脉冲序列为zg 30°,延迟时间20s,采样次数32次,窗函数0.3Hz。结果在此条件下,样品与内标盐酸吉西他滨及齐多夫定的定量峰分离良好,进样精密度及重复性较好,线性范围宽,样品与内标盐酸吉西他滨和齐多夫定质量比分别在0.354 9~1.343 9和0.312 4~1.189 2范围内,其线性拟合方程分别为：Y=1.440 9X＋0.017 8（r=1.000 0,n=5）,Y=1.634 6X＋0.008 5（r=0.999 9,n=5）。结果西他沙星的含量分别为99.26%（RSD为0.06%）和99.22%（RSD为0.17%）。结论该方法准确、专属、简便、快速,适用于该药物标准物质的绝对含量测定。

基于^(1)H-NMR的冠心病血瘀证、痰浊证的代谢组学研究

目的:冠心病以其极高的发病率严重威胁着人类的健康,对冠心病药物治疗及作用靶点的研究仍非常迫切。本研究旨在运用核磁共振氢谱(^(1)H nuclear magnetic resonance spectroscopy,^(1)H-NMR)代谢组学技术建立冠心病血瘀证及痰浊证的指纹代谢图谱,寻找这2种证型的血浆标志性代谢物,并揭示血府逐瘀汤治疗冠心病血瘀证的机制。方法:采集符合纳入标准的69例冠心病血瘀证患者、60例冠心病痰浊证患者及40例健康对照受试者的清晨空腹血浆,基于^(1)H-NMR构建冠心病血瘀证及痰浊证的^(1)H-NMR指纹代谢图谱。使用多元统计分析方法主成分分析(principal component analysis,PCA)、正交化偏最小二乘判别分析(orthogonal partial least squares discriminant analysis,OPLS-DA)寻找冠心病血瘀证及冠心病痰浊证的标志性代谢物。随机抽取冠心病血瘀证患者30例,予血府逐瘀汤治疗30 d,对治疗前后的清晨空腹血浆进行^(1)H-NMR检测,分析冠心病血瘀证患者服药前后标志性代谢物的变化。结果:冠心病血瘀证组与对照组存在显著性差异的代谢物有以下15种:3-羟基丁酸、乳酸、丙氨酸、谷氨酸、谷氨酰胺、丙酮酸、磷脂酰胆碱、甘油磷脂酰胆碱、甘氨酸、葡萄糖、苯丙氨酸、柠檬酸、酪氨酸、甲酸盐、极低密度脂蛋白,除葡萄糖、3-羟基丁酸、极低密度脂蛋白水平升高外,其他12种代谢物水平均下降。冠心病痰浊证组与对照组存在显著性差异的代谢物有以下16种:缬氨酸、乳酸、丙氨酸、N-乙酰-β-葡萄糖苷酶、谷氨酸、谷氨酰胺、丙酮酸、肌酸、胆碱、甘氨酸、葡萄糖、苯丙氨酸、柠檬酸、组氨酸、酪氨酸、甲酸盐,除葡萄糖和胆碱2种水平升高外,其他14种代谢物水平均下降。冠心病血瘀证患者服用血府逐瘀汤治疗后胆碱、磷脂/甘油磷脂类、肌酸、脂质、柠檬酸水平升高,乳酸水平下降。结论:^(1)H-NMR结合多元统计学方法能够建立诊断冠心病血瘀证和痰浊证证型的有效模型,找到证型相关标志性代谢物;血府逐瘀汤可通过调节脂质代谢、能量代谢治疗冠心病血瘀证。

Fingerprinting Analysis of Rhizoma Chuanxiong of Commercial Types using ~1H Nuclear Magnetic Resonance Spectroscopy and High Performance Liquid Chromatography Method

The ^1 H nuclear magnetic resonance （^1 H NMR） fingerprints of fractionated non-polar extracts （control substance for a plant drug （CSPD） A） from Rhizoma chuanxiong, the rhizomes of Ligusticum chuanxiong Hort., of seven specimens from different sources were measured on Fourier Transform （FT）-NMR spectrometer and assigned by comparing them with the ^1 H NMR spectra of the isolated pure compounds. The ^1 H NMR fingerprints showed exclusively characteristic resonance signals of the major special constituents of the plant. Although the differences in the relative intensity of the ^1H NMR signals due to a discrepancy in the ratio of the major constituents among these samples could be confirmed by high performance liquid chromatography analysis, the general features of the ^1H NMR fingerprint established for an authentic sample of the rhizomes of L. chuanxiong e. hibited exclusive data from those special compounds and can be used for authenticating L. Chuanxiong species.

Establishing 1H nuclear magnetic resonance based metabonomics fingerprinting profile for spinal cord injury： a pilot study

Background Spinal cord injury （SCI） is a complex trauma that consists of multiple pathological mechanisms involving cytotoxic, oxidation stress and immune-endocrine. This study aimed to establish plasma metabonomics fingerprinting atlas for SCI using 1H nuclear magnetic resonance （NMR） based metabonomics methodology and principal component analysis techniques.Methods Nine Sprague-Dawley （SD） male rats were randomly divided into SCI, normal and sham-operation control groups. Plasma samples were collected for 1H NMR spectroscopy 3 days after operation. The NMR data were analyzed using principal component analysis technique with Matlab software.Results Metabonomics analysis was able to distinguish the three groups （SCI, normal control, sham-operation）. The fingerprinting atlas indicated that, compared with those without SCI, the SCI group demonstrated the following characteristics with regard to second principal component： it is made up of fatty acids, myc-inositol, arginine, very low-density lipoprotein （VLDL）, low-density lipoprotein （LDL）, triglyceride （TG）, glucose, and 3-methyl-histamine.Conclusions The data indicated that SCI results in several significant changes in plasma metabolism early on and that a metabonomics approach based on 1H NMR spectroscopy can provide a metabolic profile comprising several metabolite classes and allow for relative quantification of such changes. The results also provided support for further development and application of metabonomics technologies for studying SCI and for the utilization of multivariate models for classifying the extent of trauma within an individual.

Prediction of Response of Collagen-induced Arthritis Rats to Methotrexate： An ~1H-NMR-based Urine Metabolomic Analysis

Over one half the patients with rheumatoid arthritis （RA） are being treated with methotrexate （MTX）. Although well proven, the efficacy of MTX varies in individual patients. This study examined the metabolic biomarkers that can be used to predict the therapeutic effect of MTX by using metabolomic analysis. Rats were immunized with collagen to rapidly cause collagen-induced arthritis （CIA） and then treated with 0.1 mg/kg MTX for 4 weeks. The clinical signs and the histopathological features of CIA were observed to evaluate the therapeutic effects. Urine samples of CIA rats were collected, and analyzed by using 600 M 1H-nuclear magnetic resonance （1H-NMR） for spectral binning after the therapy. The urine spectra were divided into spectral bins, and 20 endogenous metabolites were assigned by Chenomx Suite. Multivariate analyses were performed to identify the spectral pattern of endogenous metabolites related to MTX therapy. The results showed that the clustering of the spectra of the urine samples from the responsive rats （n=20） was different from that from the non-responsive rats （n=11）. Multivariate analysis showed difference in metabolic profiles between the responsive and non-responsive rats by using partial least squares-discrimination analysis （PLS-DA） （R2=0.812, Q2=0.604）. In targeted profiling, 13 endogenous metabolites （uric acid, taurine, histidine, methionine, glycine, etc.） were selected as putative biomarkers for predicting therapeutic response to MTX. It was suggested that 1H-NMR-based metabolomic analysis can be used to predict the therapeutic effect of MTX, and several metabolites were found to be related to the therapeutic effects of MTX.

基于细胞代谢组学技术的人参皂苷Rb1对SH-SY5Y细胞保护机制研究

采用基于1H NMR的细胞代谢组学技术探讨人参皂苷Rb1对谷氨酸诱导SH-SY5Y细胞凋亡的保护作用机制。应用MTT比色法及流式细胞术分析SH-SY5Y细胞在造模和给药前后的细胞存活率和凋亡率,利用1H NMR技术平台结合多元统计分析对细胞代谢的动态变化进行研究,揭示SH-SY5Y细胞在造模和给药前后内源性代谢物变化情况。结果表明,人参皂苷Rb1能通过减少谷氨酸诱导SH-SY5Y细胞凋亡而产生保护作用,结合正交偏最小二乘法判别分析(OPLS-DA)共鉴定出谷氨酸、牛磺酸、乙酸、精氨酸、肌酸、丙氨酸和脯氨酸共7个差异代谢物。经Metaboanalyst分析,主要涉及牛磺酸和亚牛磺酸代谢、精氨酸和脯氨酸代谢、丙氨酸、天冬氨酸和谷氨酸代谢、D-谷氨酰胺和D-谷氨酸代谢、丙酮酸代谢共5条能量代谢及氨基酸代谢途径。结果表明,人参皂苷Rb1主要通过影响多种能量及氨基酸代谢对氧化损伤的神经细胞产生保护作用。

基于T_(1)-T_(2)二维核磁共振方法研究温度对复合驱提高采收率的影响

一维核磁共振(nuclear magnetic resonance,NMR)测量方法无法分辨驱替过程中油水弛豫信号,因此采用T_(1)-T_(2)二维核磁共振测量方法分辨岩心中流体类型及分布。通过驱替实验研究聚合物BRH-325和表面活性剂GSS-A复合体系分别在65、70、75℃条件下的驱油效果,并利用纵向弛豫-横向弛豫(T_(1)-T_(2))二维NMR测量方法对岩心内部的油水两相驱替规律及分布特征进行可视化研究,并对比实验测量结果与NMR测量结果。结果表明:70℃下,复合驱提高采收率的效果最为明显。因此,T_(1)-T_(2)二维核磁共振能够直接、直观区分驱替过程中油水的弛豫信号。

葡萄糖基(α-1→6)β-环糊精的波谱学数据与结构确证

对酶法合成的葡萄糖基(α-1→6)β-环糊精的红外(IR)光谱、质谱(MS)、氢谱(1H-NMR)、碳谱(13C-NMR)、氢氢相关谱(1H1-H COSY)、氢氢完全相关谱(1H1-H TCOSY)、异核单量子相干相关谱(HSQC)和异核多键相关谱(HMBC)进行了解析报道,对所有的1H-NMR和13C-NMR谱进行了归属,讨论了红外特征吸收峰所对应的官能团的振动形式。

氯化1-甲基-3-丁基咪唑的制备与表征

用N-甲基咪唑和氯代正丁烷反应,合成了作为室温离子液体中间体的氯化1-甲基-3-丁基咪唑,对其合成过程进行优化和改进。通过核磁共振谱对氯化1-甲基-3-丁基咪唑进行化学结构的表征,使用差示扫描量热法对合成的中间体进行熔点和熔化热的测定,合成了纯度较高的氯化1-甲基-3-丁基咪唑。

4-氨基-5-[2-(4-氯苯氧甲基)苯并咪唑-1-亚甲基]-1,2,4-三唑-3-硫酮的核磁共振研究

在无水乙醇和KOH存在下,将2-(4-氯苯氧甲基)-1-苯并咪唑乙酰肼(1)与CS2反应,合成出了中间体酰肼二硫代甲酸钾盐。此中间体再与过量的水合肼反应,经环化得到一种新化合物4-氨基-5-[2-(4-氯苯氧甲基)苯并咪唑-1-亚甲基]-1,2,4-三唑-3-硫酮。采用元素分析、IR及NMR技术确定了新化合物的结构,并利用2D NMR技术对其两种异构体(硫酮和硫醇)的1H和13C NMR谱带进行了全归属,给出了相应的偶合常数J值以及异构体所占的比例。实验表明,新化合物在DMSO中存在硫酮和硫醇两种异构体的互变,并且硫酮占主导,含量为81.9%,而硫醇的含量仅为18.1%。

1—(3—吡啶甲酰)—4—芳基氨基硫脲类和3—(3—吡啶基)—4—芳基—1,2,4—三唑啉—5—硫酮类化合物^(13)C—NMR谱研究

本文测定了1-(3—吡啶甲酰)—4—苯基氨基硫脲、3—(3—吡啶基)—4—苯基—1,2,4—三唑啉—5—硫酮等8个新化合物的^(13)C NMR谱,运用质子宽带去偶、偏共振去偶,结合信号强度对比、苯基取代基效应的计算,同时与模型化合物对照,一一归属了其谱峰。本文对这两类化合物之间的^(13)C NMR谱差异进行了探讨,并得到了在吡啶环3位取代的甲酰肼基对吡啶环各碳取代基效应的数据。

葡萄糖转运蛋白-1-Ag@Mn探针的合成及在胰腺癌细胞靶向成像中的应用

目的构建偶联葡萄糖转运蛋白-1(GLUT-1)、锰离子及荧光染料Cy5. 5的核酸银纳米探针,探讨其在胰腺癌细胞靶向成像中的应用。方法以单链DNA为模板合成核酸银纳米簇,通过碱基互补配对及静电吸附偶联GLUT-1核酸适配体、Mn离子,在其表面连接Cy5. 5,形成GLUT-1-Ag@Mn纳米探针;透射电镜检测纳米探针的均匀性及分散性; CCK-8检测共培养小鼠成纤维细胞及人胰腺癌细胞的增殖活性;激光共聚焦成像检测纳米探针的靶向性; 3. 0T核磁共振体外成像检测其对T1加权成像的信号增强效应。结果透射电镜提示纳米探针水溶性好、分散性高,粒径小而均一; CCK-8检测提示各组细胞的存活率均大于90%,各组间细胞存活率差异无统计学意义(P> 0. 05)。激光共聚焦成像提示纳米探针能够更多的靶向高表达GLUT-1 Pa Tu8988细胞。MRI T1WI体外检测提示,纳米探针能增高Pa Tu8988细胞T1WI信号强度。结论 GLUT-1-Ag@Mn纳米探针具有良好的生物相容性及理化性质,可靶向检测高表达GLUT-1的胰腺癌细胞,增高T1WI信号强度,有望为胰腺癌早期诊断提供依据。

核磁共振录井技术在巴1井的应用

核磁共振录井技术以其独特的优势被选择进入巴1井录井系列之中。在简单介绍核磁共振录井原理后,从储层物性评价、油气水层解释等方面阐述了核磁共振录井资料在巴1井的应用情况:核磁物性分析与室内常规物性分析数据具有良好的相关性,核磁数据能够较好地评价储层物性;结合其它地区经验,建立了评价巴1井储层物性、储层流体性质评价的方法、标准;运用这些标准,对巴1井7层显示层进行解释评价,试油结论与评价成果一致。

核磁共振方法表征2,2'-二(对羧酸苯氧基)-1,1'联萘

利用１Ｈ ＮＭＲ，１３Ｃ ＮＭＲ研究了 ２，２’－二（对羧酸苯氧基）－１，１’－联萘结构，并通过１Ｈ－１Ｈ ＣＯＳＹ及１３Ｃ－１Ｈ异核相关谱进一步确定了其１Ｈ谱和１３Ｃ谱中各谱峰的归属，为同类化合物的表征提供了一个依据。

2,2'-二(对胺苯甲酯)-1,1'联萘的核磁共振谱解析

利用~1HNMR,^(13)CNMR谱研究了2,2’-二(对胺苯甲酯)-1,1’联萘的结构,并通过~1H-~1HCOSY,^(13)C-~1H异核相关及^(13)C-~1H异核远程相关谱进一步地确定了~1H谱和^(13)C谱中各谱峰的归属,为同类化合物的表征提供了一个依据.

单纯疱疹病毒1型感染神经胶质细胞的代谢组学研究

目的研究单纯疱疹病毒1型(HSV-1)对人类少突胶质细胞(OL细胞)代谢的影响,从而探讨HSV-1感染的分子机制。方法将OL细胞随机分为两组,一组为感染组,感染HSV-1,一组为正常对照组,不感染HSV-1,运用核磁共振氢谱(~1H NMR)检测二组细胞培养液水相代谢产物,最后由偏最小二乘法-判别分析(PLS-DA)对数据进行分析。结果感染组与正常对照组细胞培养液水相代谢物的组成有显著差异:被HSV-1感染的OL细胞的培养液中,亮氨酸、谷氨酸、谷氨酰胺增多,丙氨酸、甘氨酸、组氨酸、异亮氨酸、乳酸减少。结论 HSV-1感染改变OL细胞的氨基酸代谢,HSV-1可能通过扰乱宿主细胞的代谢路径,促进自己的繁殖,并影响神经系统的功能活动。