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??Cardiac hypo-function caused by myocardial ischemia is considered as the first killer of human health. The related metabolites in body can be changed due to the lack of blood and oxygen. These metabolites generated by pathological and physiology changes or exogenous intervention are extreme complicated, and the existing test methods can??t satisfy the prospected purpose due to the lower sensitivity, more narrow liner range and so on. Therefore, the concept of metabonomics, a systemic analysis method, was put forward. Metabolites can be quantified in temporal and spatial dimension by metabonomics featured in a high throughput, higher detective sensitivity and wider liner range manner. So it has gradually been applied to many areas including myocardial ischemia. In this paper, based on the comprehensive research literature in domestic and overseas in recent years, the application of metabonomics in pharmacological research of myocardial ischemia was summarized. Five kinds of metabolic pathways are related with myocardial ischemia including sugar metabolism, energy metabolism, amino acid metabolism, purine metabolism and soluble epoxide hydrolase table oxidase P450 metabolism. Some drugs can be used to myocardial ischemia via these pathways. These representative drugs and their mechanisms which are analyzed by metabonomics were concluded in this paper.     

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??The rapid development of modern analytical technology provides many methods of detecting drugs and their metabolites. LC-MS/MS technology has become one of the most commonly used methods in drug metabolites analysis with its characteristics of simpleness and high efficiency. In this paper, based on the published articles of in vivo drug metabolites study by LC-MS/MS in recent years, the processes of data acquisition and processing, metabolites detecting and identification and software-assisting were summarized. This article provides references for research on drug metabolism using LC-MS/MS.     

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??The metabolic profile of bile acids (MPBA) is an indicator that reflecting the varieties, contents and variations of biological bile acids (BAs). Many kinds of detection techniques can be used to detect different kinds of BAs in different tissues. By using various detection techniques, the MPBA has been applied in various diseases such as hepatobiliary diseases, gastrointestinal diseases, metabolic diseases and nervous system diseases and so on. In this paper, we reviewed the process of BAs synthesis and metabolism and analyzed the detection techniques of BAs in different tissues and the corresponding MPBA. At the same time, we summarized the application of BAs metabolism in related diseases. The MPBA provides a reference for the diagnosis and treatment of some diseases and it has certain advantages in disease diagnosis and curative effects evaluation, which worth further study.     

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??To summarize the research progress of the regulation of lipid metabolism by citrus flavonoids. Recent research articles were analyzed and summarized. Citrus flavonoids are mainly flavanones and polymethoxyflavones, and they can regulate lipid metabolism and prevent atherosclerosis in vitro and in vivo. Factors such as different flavonoid profiles, dosage, time, and experimental models all affect the effectiveness. Citrus flavonoids have great application potentials in regulation of lipid metabolism in vivo, and it has both theoretical and practical significance to screen and study citrus flavonoids.     

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??Antitumor drugs have the characteristics of low therapeutic index, narrow safety window, and so on, which are prone to have toxic and side effects in the course of clinical therapy, thus limiting their use. In recent years, some studies have pointed out that the mechanism of adverse reactions of antitumor drugs is related to drug metabolism enzymes, receptors and transporters. Among them, drug metabolism enzymes and their gene polymorphisms play an important role in the toxic and side effects of antitumor drugs. In this paper, we analyze and summarize the side effects of antitumor drugs mediated by drug metabolism enzymes, mainly from the aspects of the roles of metabolic enzymes and their gene polymorphism in the metabolic activation and metabolic detoxification of antitumor drugs, in order to effectively avoid or reduce the toxic side effects of antitumor drugs, and to provide a reference for individualized treatment of cancer.     

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??OBJECTIVE To design and synthesize brain targeting danshensu (DSS) derivatives and study their metabolism in rat plasma and brain homogenate in vitro. METHODS Tetramethylpyrazine and its derivatives were selected as carriers to design the brain targeting danshen suderivatives. Lipid-water partition coefficient (logP), brain blood concentration ratio (BB), and P-glycoprotein affinity of the derivatives were predicted by some calculation softwares and the better compound DT3 was chosen for the next synthesis. The degradation of DT3 and its intermediate DT1 in rat plasma and brain homogenate were measured by HPLC-UV. RESULTS Two danshensu-pyrazine ester derivatives were synthesized, ie DT1 and DT3. A simultaneous determination method of DT3, DT1, and (3,5,6-trimethylpyrazine-2-yl)methanol (TMPM) in rat plasma and brain homogenate was established. The degradation of DT3 in rat plasma and brain homogenate underwent the following processDT3??DT1??the active metabolites of DSS and TMPM.Compared with DT1, the degradation of DT3 in rat plasma slowed down.The half-lives (t_1/2) of TMPM were 1.68 and 1.71 min, respectively. Also,DT3 could quickly release the active metabolitein rat brain homogenate, and the concentration of TMPM showed a steady increase with a t_1/2 of 222.88 min. CONCLUSION The danshensu-pyrazine ester derivative DT3 has an extended t_1/2 in rat plasma, and it can be degraded to active metabolite quickly in rat brain homogenate.     

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??OBJECTIVE To investgate the protective effects and mechanisms of Polygonatum kingianum on nonalcoholic fatty liver induced by high-fat diet in rats. METHODS A total of 42 rats were randomly divided into normal control group (normal saline), model group (normal saline), resveratrol group (positive control, 40 mg??kg^-1) and low-, middle-and high-dose P. kingianum group (1, 4, 8 g??kg^-1). They were intragastrically given corresponding compounds (or normal saline) once a day, lasting for 14 weeks. Nonalcoholic fatty liver was induced by feed with high-fat diet for 14 weeks in those groups except for normal control group. Blood was taken from the corneas at 0, 6, 12 and 14 week, and then the levels of triglyceride (TG) and total cholesterol (TC) in serum were determined. Afterword, the rats were sacrificed at 14 week followed by the measurement of organs indices of liver??spleen and kidney, as well as the detection of levels of TC, TG, high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C) in liver tissues. Furthermore, the levels of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), ATP synthase and respiratory chain complex ?? and ?? in hepatic mitochondria were determined. RESULTS Nonalcoholic fatty liver was successfully induced by high-fat diet in rats. The different doses of water extract of P. kingianum could significantly inhibit the increasing of liver index and serum TC in high-fat diet-induced rats, alleviate swelling, degeneration, necrosis and inflammatory injury of hepatic cells, inhibit the increasing of TC, TG and LDL-C and decrease of HDL-C in liver tissues, as well as inhibit the exaltation of MDA level and reduction of SOD, GSH-PX, ATP synthase and respiratory chain complex ?? and ?? activity in hepatic mitochondria. CONCLUSION P. kingianum shows protective effects on high-fat diet-induced nonalcoholic fatty liver in rats. The action mechanism may be related to the elimination of oxidative stress product (MDA) and improvement of antioxidant enzyme activity (SOD and GSH-PX) in hepatic mitochondria, as well as the improvement of energy metabolism obstacle.     

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??High-dose methotrexate can obviously reduce tumor recurrence and prolong disease-free survival. But in actual clinical use, the pharmacokinetics and toxicity of the drug show large interpatient variability. Metabolic enzyme and transporter gene polymorphisms may be one of the important influence factors, which are the research focus in recent years. However, different research shows various results. We reviewed the results of related literatures in recent years and the influence of gene polymorphisms of metabolic enzyme and transporter on pharmacokinetic and toxicity of methotrexate were summarized, which can provide information support for the further study of the individualized treatment of methotrexate.     

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??OBJECTIVE To systematically review the bone metabolism in the epileptic patients receiving oxcarbazepine monotherapy. METHODS Literatures were searched from Pubmed, EMbase, Cochrane Library, CNKI, VIP, Wanfang and CBM database. The included studies were all cohort studies. The quality of studies was evaluated according to the Newcastle-Ottawa Quality Scale (NOS scale). Meta-analysis was performed by the Cochrane Collaboration??s software RevMan5.3. RESULTS Eleven cohort studies were included, all of which were high quality researches (7-8 according to NOS scale). Compared with the control group, serum calcium and 25-OH-VitD declined in the OXC group (P<0.05). In less than half a year of therapy, the 25-OH-VitD level in the OXC group was lower than the control group (P<0.05), but no statistical difference for the serum calcium (P>0.05). In more than half a year of therapy, the serum calcium level in the OXC group was lower than the control group (P<0.05), but no statistical difference for the 25-OH-VitD (P>0.05). For children in the OXC group, both the serum calcium and 25-OH-VitD were decreased (P<0.05) while there was no statistical difference for adults (P>0.05). Besides, all of the serum phosphorus, parathyroid hormone, osteocalcin were not statistically different between the OXC and control groups (P>0.05). In more than half a year of therapy, parathyroid hormone rose above the control group (P<0.05), while both the therapy duration and age of the therapy subjects had no influence in the remaining indexes. Moreover, there was no statistical difference between the two groups for the bone mineral density in different body parts (P>0.05). CONCLUSION Oxcarbazepine may reduce serum calcium and serum 25-OH-VitD, especially for children. Regardless of age, the serum 25-OH-VitD may decline in less than half a year of therapy, while the serum calcium may decline and parathyroid hormone may increase in more than half a year of therapy. Oxcarbazepine had no significant effect on the serum phosphorus, osteocalcin and bone mineral density. All of the included studies in this article are cohort studies with certain limitations as a result of bias risk.     

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??Urotensin ?? (U??) and urotensin ?? receptor (UTR) have significant effects on the pathogenesis of type 2 diabetes (T2D). UTR, as a G protein-coupled receptor (GPCR), mediates U?? signal transduction.The gene polymorphism of U?? and UTR is high related to the susceptibility of diabetes, suggesting a relationship between U?? system and T2D. U?? system can influence the process of T2D by affecting body weight, lipid and glucose metabolism and inflammatory response. U?? can also induce insulin resistance by regulating insulin-related signaling pathway or accelerating oxidative stress.Therefore, U?? system might be a potential target for T2D treatment.     

菟丝子总黄酮的提取方法筛选及其雌激素活性研究

目的 优选菟丝子总黄酮的最佳提取方法,并对提取物的雌激素活性进行测定.方法 用紫外分光光度法测定菟丝子总黄酮的含量,并以此作为评价指标,采用L4(23)正交设计实验对超声提取、回流提取及闪式提取法进行工艺优化和筛选;并采用性未成熟小鼠子宫增重和子宫(苏木精-伊红)(HE)染色法,以小鼠的子宫系数和子宫内膜厚度评价菟丝子...     

响应面法优化大孔树脂纯化菟丝子总黄酮工艺

目的 优化大孔树脂纯化菟丝子总黄酮工艺。方法 采用单因素实验,以总黄酮、金丝桃苷的吸附率和解析率为指标,筛选最佳大孔树脂型号。以总黄酮、金丝桃苷吸附量为指标,考察吸附时间、漏点浓度、上样液pH对纯化工艺的影响。以总黄酮、金丝桃苷洗脱率为指标,考察洗脱液流速、洗脱液体积、洗脱液浓度对纯化工艺的影响。在此基础上,以总黄酮与金丝桃苷含量的归一值为指标,利用Box-Behnken响应面法优化并确立最佳工艺。结果 菟丝子总黄酮纯化的最佳树脂型号为AB-8型,最佳工艺条件为:上样液pH 3.9、洗脱液体积19.6BV,洗脱液浓度74%,验证实验的总OD值为0.982 5,与模型预测值接近。纯化前后,总黄酮含量由18.95 mg·g^-1提高至85.68 mg·g^-1,金丝桃苷含量由4.12 mg·g^-1提高至16.85 mg·g^-1。结论 优选的纯化工艺方法稳定、可行,可用于菟丝子总黄酮的纯化。     

基于UHPLC-Q-TOF-MS/MS和LTQ-MSn联用技术快速鉴定绞股蓝皂苷类化学成分

目的 建立超高液相色谱-飞行时间高分辨质谱(UHPLC-Q-TOF MS/MS)和超高液相线性离子阱质谱(LTQ-MSⁿ)联用技术对绞股蓝中皂苷类成分快速鉴定的方法。方法 采用Thermo Syncronis C₁₈(2.1 mm×100 mm,1.7 μm)色谱柱,以纯水-乙腈为流动相梯度洗脱,质谱采用电喷雾(ESI)离子源,在负离子模式下采集数据对绞股蓝皂苷类进行成分鉴定。结果 初步鉴定了81种绞股蓝皂苷,其中包括58种已知皂苷和23种可能的未知皂苷结构。结论 UHPLC-Q-TOF-MS/MS可以提供化合物的准确相对分子质量及二级碎片信息,LTQ-MSⁿ可以提供化合物多级质谱信息,该联用技术可以简单、快速鉴定绞股蓝皂苷类成分,并为其质量控制、药效物质基础研究及进一步临床应用提供理论依据和科学研究思路。     

基于UPLC-ESI-Q-TOF-MS/MS技术快速鉴定彝族药双参的化学成分

目的 应用超高效液相色谱-电喷雾/四极杆飞行时间串联质谱(UPLC-ESI-Q-TOF-MS/MS)技术快速鉴定双参药材的化学成分。方法 采用Acquity UPLC BEH C₁₈色谱柱(2.1 mm×100 mm, 1.7μm)分离,以体积分数0.1%甲酸水溶液(A相)-乙腈(B相)为流动相进行梯度洗脱,流速0.4 mL·min^-1,采用电喷雾离子源(ESI),在正、负离子模式下采集数据,扫描范围m/z 100～2 000,通过与对照品的保留时间及质谱数据信息对比,并结合精确相对分子质量、质谱裂解规律、质谱数据库(ChemicalBook, ChemSpider, Pubmed等)及相关文献,对双参的化学成分进行快速鉴定。结果 从彝族药双参中共鉴定出59个化合物,其中包括11个环烯醚萜类、23个有机酸类、14个三萜类、4个糖苷、其他类(1个香豆素类、1个生物碱类、2个酯类、1个多酚类、2个核苷类),其中通过与对照品对比鉴定了8个化合物,分别为绿原酸、隐绿原酸、异绿原酸A、异绿原酸B、异绿原酸C、马钱苷、马钱苷酸和樟芽菜苷。结论 该研究首次...     

基于UHPLC-LTQ-Orbitrap-MS/MS技术快速分析保心宁胶囊中的化学成分

目的 建立高效,稳定的超高效液相色谱-线性离子阱轨道阱串联质谱联用(UHPLC-LTQ-Orbitrap-MS/MS) 方法,系统、全面地定性分析中药制剂保心宁胶囊中的化学成分组成。为保心宁胶囊质量控制方法的开发,标准的完善以及临床应用提供依据。方法 采用UHPLC-LTQ-Orbitrap-MS/MS对保心宁胶囊中的化学成分进行快速分析。通过UHPLC-LTQ-Orbitrap-MS/MS扫描的到的化合物精确分子量,对照品和多级碎片离子信息,并结合相关文献以及裂解规律,实现对保心宁胶囊的准确定性分析。结果 共鉴定出103种化学成分,包括萜类、皂苷类、酚酸类、黄酮类、有机酸类、香豆素类、苯酞类及姜黄素类等,并对化合物的药材归属进行了分类。结论 本研究建立了对保心宁胶囊中化学成分的快速定性分析的方法,为保心宁胶囊的质量评价指标及药效物质基础研究提供参考。     

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??OBJECTIVE To analyze the differences in chemical composition of Magnolia officinalis var. biloba Rehd. et Wils from different commercial specifications. METHODS The difference in chemical constituents of Magnolia officinalis var. biloba Rehd. et Wils from different commercial specifications was analyzed by LC-Triple TOF MS/MS combined with multivariate statistical analysis. Through analysis of the multistage tandem mass spectrometry, the characteristic peaks were extracted with mass spectrometry data peak matching, peak alignment, and noise filtering. Principal component analysis(PCA)and partial least-squares discriminant analysis(PLS-DA)were used for data processing. The components were identified according to MS accurate mass and MS/MS spectrometry fragmentation information, combined with the database search and literature. RESULTS The chemical constituents in Magnolia officinalis var. biloba Rehd. et Wils from different commercial specifications were clearly distinguished. Twenty-two chemical constituents had significant differences. Among them, 10 kinds of common different chemical constituents, such as leonoside A, syringaresinol-4'-O-??-D-glucopyranoside, magnolignan D, magnolignan A or C, randaiol, honokiol, obovatol, magnolignan G,(??)9-HODE and piperitylmagnolol, presented different changing laws. CONCLUSION This study can provide references for establishment of a mathematical model for prediction of the specifications of chemical information of Magnoliae Officinalis Cortex based on metabolomics and comprehensive evaluation of the quality of medicinal herbs.     

基于UPLC-Q-TOF-MS/MS技术的彝族药姜味草化学成分分析

目的 应用超高效液相色谱-串联四级杆飞行时间质谱联用技术(UPLC-Q-TOF-MS/MS)对彝族药姜味草中的化学成分进行定性分析。方法 Waters Acquity UPLC BEH C₁₈色谱柱(2.1 mm×100 mm,1.7 μm),以乙腈(A)-体积比0.1%甲酸水溶液(B)梯度洗脱,质谱分析采用信息关联模式(IDA),在正、负离子模式下采集数据。结果 根据化合物的精确分子质量和碎片离子信息,结合对照品比对和文献数据,从姜味草中鉴定推断出77个化学成分,包括黄酮类27个、有机酸类21个、苯丙素类8个、三萜酸类8个、氨基酸类6个,其他类:蒽醌类、环烯醚萜类、醇类等7个。结论 首次对姜味草中的化学成分进行快速鉴别,为其质量控制及药效物质基础提供了科学依据。     

基于超高效液相色谱-四极杆飞行时间质谱技术的洋川芎内酯H在大鼠体内的代谢产物分析

目的 采用超高效液相色谱-四极杆飞行时间质谱(UHPLC-Q-TOF-MS)技术对洋川芎内酯 H 在大鼠体内的代谢产物进行分析鉴定。方法 SD大鼠灌胃给药后,收集其血浆、尿液、胆汁和粪便,并对样品进行前处理。采用ThermoAccucore C₁₈色谱柱(2.1 mm×150 mm,2.6 μm),以体积分数0.1%乙酸-水(A相)-乙腈(B相)作为流动相进行梯度洗脱。根据准分子离子峰和碎片离子信息,结合对照品与文献报道,对大鼠血浆、尿液、胆汁和粪便中的原型成分及其代谢产物进行鉴定。结果 最终在大鼠血浆、尿液、胆汁和粪便中共检测到32个代谢产物,包括24个Ⅰ相和8个Ⅱ相代谢物。结论 洋川芎内酯 H 主要的体内代谢反应包括氧化、氢化、去羟基化、甲基化、葡萄糖醛酸化、硫酸酯化、半胱氨酸结合、谷氨酰胺结合以及相关的复合反应等。本研究应用高分辨液质联用技术阐明了洋川芎内酯 H 在大鼠体内的代谢产物,为今后药效学和药理学研究奠定了基础。     

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??OBJECTIVE To establish a novel ultra-high performance liquid chromatography-quadrupole/orbitrap high resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS) method to study the chemical composition of Naoxintong capsules rapidly and accurately. METHODS The information of accurate mass in full-MS and multistage fragment ions was obtained by the novel UHPLC-Q-Orbitrap technology. Chemical constituents were identified by comparing the relative retention time and the mass data of the reference substances, meanwhile consulting the reference literature or the Mass Bank, Chemical Book network database. RESULTS Forty-four compounds were finally identified in this study, mainly including flavones, authraquinones, terpenoids and organic acids. CONCLUSION A method is established in this study to identify various chemical constituents of Naoxintong capsules rapidly, accurately and systematically. What's more, our research will lay a sound theoretical foundation and propose a scientific study idea for the quality control improvement, bioactive components recognition and further clinical application of this herbal formulation.     

基于UPLC-QTOF-MS结合多元统计的不同干燥方法白术中化学成分差异分析

目的 建立超高效液相色谱-四极杆飞行时间质谱联用技术(UPLC-QTOF-MS)结合多元统计分析技术的分析方法,比较不同干燥方法对白术中化学成分的影响。方法 采用UPLC-QTOF MS进行分析,对采集的图谱进行峰匹配、峰对齐、滤噪处理等进行特征峰提取,分别采用热图聚类分析、主成分分析(PCA)和偏最小二乘法-判别分析(PLS-DA) 对数据进行分析。结果 不同干燥白术样品在PCA轴上呈逐步变化的趋势,能有效的区分,与热图的Pearson聚类结果一致,分类结果较为理想;建立的PLS-DA模型结果较好,各样品中化学成分差异明显,根据一级质谱精确质荷比和二级质谱碎片信息,结合软件数据库搜索及相关文献进行成分鉴定,初步鉴定出34种化学成分,并筛选出白术内酯I、苍术醇、白术内酯Ⅱ、芹烷二烯酮、苯乙酸对羟基苯乙酯、白术内酯I(同分异构)、呋喃倍半萜、白术内酯Ⅳ、绿原酸、白术内酯Ⅲ这10种区分不同干燥方法的特征性成分,并呈现出不同的变化规律。结论 本研究成果为揭示不同干燥方法对白术代谢产物的影响规律及探讨白术药材的品质形成机制提供基础资料。