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??OBJECTIVE To investigate the therapeutic effects metabolic mechanism of Schisandra chinensis polysaccharide (SCP) on chronic fatigue syndrome (CFS). METHODS CFS rat model was established in a variety of ways such as the bondage, excessive exercise, crowded and noise environment. The Morris water maze test, the open-field test and the tail-suspension test were performed to evaluate the CFS model. The gas chromatography-mass spectrometry (GC-MS) method was conducted to screen the different metabolites in rat urine and analyze the metabolic pathway. RESULTS The body weight of rats were increased and their space exploration and memory ability were strengthened after SCP supplement. The eleven diversity urine metabolites were detected and the involved metabolic pathways were the tricarboxylic acid cycle and the alanine, aspartic and glutamic acid metabolic pathways. CONCLUSION SCP could relieve the chronic fatigue syndrome. The metabolic mechanism is relative to the improvement of SCP on the tricarboxylic acid cycle and the alanine, aspartic and glutamic acid metabolic pathways.     

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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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??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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??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 study the flavonoid glycosides of Urena lobata. METHODS Compounds were isolated and purified using various column chromatographies such as D101 macroporous adsorption resin, silica gel, Sephadex LH-20, and prep HPLC. Their structures were identified on the basis of their physicochemical properties and various spectroscopic experiments, including HRESIMS, ¹H-NMR, ¹³C-NMR, HSQC, and HMBC. RESULTS Ten flavonoid glycosides were obtained from the n-BuOH extract of U. lobata including quercetin-3-O-??-D-glucopyranosyl-(1??2)-??-D-galactopyranoside(1), kaempferol-3-O-??-D-glucopyranosyl-(1??2)-??-D-glucopyranosyl-7-O-??-L-rhamnopyranoside(2), quercetin-3-O-??-D-apiofuranosyl-(1??2)-??-D-glucopyranosyl-7-O-??-L-rhamnopyranoside(3), kaempferol-4'-O-??-D-apiofuranosyl-3-O-??-D-glucopyranosyl-7-O-??-L-rhamnopyranoside(4), kaempferol-3-O-??-D-apiofuranosyl-(1??2)-??-D-glucopyranosyl-7-O-??-L-rhamnopyranoside(5), quercetin-3-O-??-D-glucopyranosyl-7-O-??-L-rhamnopyranoside(6), quercetin-3-O-??-D-glucopyranosyl-(1??2)-??-D-glucopyranoside(7), kaempferol-3-O-??-L-rhamnopyranosyl-(1??6)-??-D-glucopyranosyl-(1??2)-??-D-glucopyranoside(8), kaempferol-3-O-??-D-glucopyranosyl-(1??2)-[??-L-rhamnopyranosyl-(1??6)]-??-D-glucopyranoside(9) and kaempferol-3-O-??-D-glucopyranosyl-(1??2)-??-D-glucopyranoside(10). CONCLUSION Compounds 1-3 and 6-10 are firstly obtained from U. lobata.     

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??OBJECTIVE To evaluate the effect of Polygonatum odoratum polysaccharide(POP) on hyperthyroidism Yin-deficiency rats based on GC-MS metabolomics and explore its mechanism. METHODS SD rats were randomly divided into control, model and POP groups. The hyperthyroidism Yin-deficiency rats were treated by intraperitoneal injection of T3 for a week. The content of T3??T4 in serum and cAMP??cGMP in plasma was determined. A GC-MS based metabolic profiling method was employed to analyze the distinctive metabolic patterns of serum in control, model and POP. Multivariate statistical analysis was applied for multivariate analysis to find potential biomarkers of Yin-deficiency by SIMCA-P 12.0 software. RESULTS Compared with the model group, polygonatum polysaccharide can significantly reduce the content of T3, T4, cAMP, the ratio of cAMP/cGMP and increase the content of cGMP, indicating it has certain Yin-nourishing action. The PCA score plot showed metabolic profiling of control, model and POP had significant differences. Nine potential biomarkers were identified by PLS-DA and variable importance for project values(VIP) based on the metabolomics. CONCLUSION The endogenous metabolites were changed by POP intervention significantly in Yin-deficiency rats, and the preventive role may be related to the synergism of glucose and lipid metabolism, amino acid metabolism, energy metabolism with the multi-targets, which provides a basis for further study of the mechanism of POP treatment of Yin-deficiency.     

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??OBJECTIVE To investigate the mechanism of hyperthyroid rats treated by thiamazole tablets by the serum metabonomics technology. METHODS Hyperthyroid rats were modeled by subcutaneous injection of L-levothyroxine sodium 35 ??g??100 g^-1 for 7 d. Then rats of thiamazole-treated group were treated by intragastric administration of thiamazole tablets suspension 21 mg??kg^-1 for 21 d. The serum levels of model rats, control rats, thiamazole-treated rats were analyzed by using UPLC-QTOF-MS and UPLC-QTOF-MS was combined with two different modes of positive and negative ions as well as KEGG and HMDB. RESULTS Compared with normal rats, among hyperthyroid rats oxalacetic acid, dihydroxyacetone phosphate (DHAP), ethyl glucuronide, leukotriene E3, hydroxykynurenine, triglycerides (TG) and lysophospholipids were increased. Meanwhile, diacylglycerol (DG) and phosphatidylinositol (PI) were decreased. The 21 d later, the metabolism levels of oxalacetic acid, dihydroxyacetone phosphate, leukotriene E3, phospholipids and fatty acids in thiamazole-treated rats were close to the normality. CONCLUSION The RESULTS infer that tricarboxylic acid cycle of hyperthyroid rat is disturbedall of glucose metabolism, lipid metabolism and amino acid metabolism get into disorder. And these disorders are improved certainly by treating thiamazole. Meanwhile, this method provides an available reference for the establishment of the means of diagnosing hyperthyroidism based on metabonomics and the assessment of the therapeutic effect of thiamazole tablets.     

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??OBJECTIVE To investigate the risk of magnolol interfering into propofol glucuronidation in human.METHODS This study was performed in pooled microsomes from human liver, intestine and kidney (HLM, HIM, HKM, respectively). Kinetic analyses were conducted to gain the inhibition potentials of magnolol against propofol glucuronidation in HLM, HIM, and HKM.RESULTS Magnolol can potently inhibit propofol glucuronidation in HLM and HKM, following mixed inhibition kinetics with K_i values of 0.1 and 0.2 ??mol??L^-1, respectively. Different from HLM and HKM, propofol glucuronidation in HIM was not affected by the presence magnolol. CONCLUSION Magnolol is hardly to depress systemic propofol glucuronidation due to lack of inhibition of the intestinal metabolic pathway.     

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??OBJECTIVE To explore the antitumor effect and immunity change of Periplaneta americana C??3 and related synthetic peptide HFDT1 in mice and to provide a base for clinical application of the materials. METHODS Sixty BALB/c mouse tumor model with leukemia L1210 were established and divided into five groups. The mice were treated with Periplaneta americana C??3 high dose, low dose, HFDT1, CTX and normal saline for 10 d, respectively. Twelve mice were as normal control group. The tumor inhibition rates and weight of body were observed in different groups. Then the results were observed including thymus and spleen index, the numbers of immune cells in peripheral blood, the ratio of splenic total lymphocytes, splenic B cell(CD45R⁺)and T cell(CD3⁺), T cell subset(CD3⁺CD4⁺ and CD3⁺CD8⁺ T cell), and the levels of IgG, IgA and IgM in serum through weight, auto-analysis of blood cell, flow cytometry, sandwich-antibody ELISA from thymus, spleen, peripheral blood in the mice. RESULTS The results showed that C??3 and HFDT1 inhibited the growth of mouse L1210 tumor and maintained the mouse weights. They increased the mouse thymus indexes and spleen indexes effectively and the numbers of peripheral blood immune cells. They maintained the spleen lymphocyte and regulated the ratio of T and B lymphocytes, CD3⁺CD4⁺ T cell and CD3⁺CD8⁺T cell. They increased the levels of serum IgG, IgA and IgM. CONCLUSION Periplaneta americana extract C??3 and related synthetic peptide HFDT1 have a strong inhibition effect to tumor. The antitumor effect of C??3 and HFDT1 may be achieved through to improve immune function. They are hoped to become efficient and low toxicity antitumor drugs. Especially HFDT1, it has an extensive application because it can be synthesized by artificial methods.     

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??OBJECTIVE To investigate the differences of the accumulation of the main secondary metabolites in the leaves of 11 kinds of Paris L. medicinal plants. METHODS The contents of the main secondary metabolites, polyphyllin??, ??, ??, and ?? in the leaves of 11 kinds of Paris L. medicinal plants were determined by UPLC, and the UPLC fingerprints were established. The accumulation of the main secondary metabolites was evaluated by one-way ANOVA and chromatographic analysis. RESULTS There was significant difference(P<0.01)in the contents of polyphyllin ??, ??, ??, and ?? in the leaves of 11 kinds of Paris L. medicinal plants, and polyphyllin ??, ??, ??, ?? were simutaneously detected only in var. yunnanensis-1, P. axialis, P. thibetica, P. forrestii and var. yunnanensis; there was significant difference in the UPLC chromatograms of 11 kinds of Paris L. medicinal plants, but the similarities among var. yunnanensis-1, P. axialis, P. thibetica, P. forrestii and var. yunnanensis all reached 0.902 with 16 common peaks, indicating smaller difference in their main secondary metabolites. CONCLUSION There is significant difference in the abilities of the 11 kinds of Paris L.medicinal plants to accumulate polyphyllin ??, ??, ??, and ?? , which may be the main reason that there are significant differences in the contents and classes of the major secondary metabolites of Paris L. roots.     

肾阳虚外感小鼠模型的建立及评价

目的:建立肾阳虚外感复合病证小鼠模型.方法:腹腔注射苯甲酸雌二醇注射液(0.008 mg·g-1),复制小鼠肾阳虚模型.在此基础上,采用鼠肺病毒株FM1滴鼻建立肾阳虚小鼠外感模型,观察小鼠体征表现,死亡率及每天体重、游 泳时间、肛温变化;测定小鼠血清肿瘤坏死因子-α(TNF-α),干扰素-γ(IFN-γ)含量;并观察肺组织病理变化;测肾、肺、脾、肾上腺及胸腺的脏器指数.结果:模型组小鼠游泳时间、肛温、趾温、自主活动均明显下降(P＜0.01);肺组织出现外感病毒性肺炎的特征;与正常对照组比较,模型组小鼠各脏器指数均降低,其中胸腺具有显著性差异(P＜0.01);IFN-γ含量明显提高(P＜0.05);TNF-α含量有降低趋势.结论:采用雌二醇腹腔注射结合鼻腔滴注流感病毒FM1,病证结合建立的肾阳虚外感病证小鼠模型,在一定程度上反映了中医肾阳虚外感的特点,为研究肾阳虚外感的发病机制及药物干预提供了较理想的实验模型.     

麻黄细辛附子汤对肾阳虚外感模型小鼠的干预作用

目的:探讨麻黄细辛附子汤对肾阳虚外感模型小鼠的干预作用。方法:采用腹腔注射苯甲酸雌二醇(8 mg.kg-1)法复制肾阳虚小鼠模型,按体温随机分成模型组、利巴韦林0.312 5 g.kg-1组及麻黄细辛附子汤低、中、高(2.5,12.5,25g.kg-1)组,另设正常对照组。采用鼠肺病毒株FM1滴鼻建立肾阳虚小鼠外感模型。感染1 d后给药,给药6 d,每日1次,观察小鼠的死亡数和死亡时间,比较肺指数,各组动物肺组织切片HE染色,观察肺组织的炎症病变;采用酶联免疫吸附法(ELISA)检测,血清干扰素-γ(IFN-γ)和肿瘤坏死因子-α(TNF-α)水平。结果:与模型组比较,不同剂量麻黄细辛附子汤有降低感染小鼠死亡率的趋势;给药后小鼠肛温显著回升(P<0.05),有效改善肺组织病毒性肺炎的病理损伤;能降低流感病毒感染小鼠的肺指数(P<0.05);麻黄细辛附子汤中、高剂量组治疗后,血中TNF-α水平显著升高(P<0.05)。结论:麻黄细辛附子汤能够明显的延长肾阳虚外感小鼠的平均生存时间,升高小鼠体温,改善体征,对小鼠流感肺炎症状的减轻、机体非特异性免疫功能的增强具有一定的效果,为临床用于流感的治疗提供了现代药理学依据。     

基于粪便代谢物组学分析麻黄细辛附子汤干预H1N1流感病毒感染小鼠的作用机制

目的:运用代谢组学方法研究麻黄细辛附子汤(Mahuang Xixin Fuzi Tang,MXF)干预H1N1流感病毒感染小鼠粪便样品中内源性物质的变化,寻找与疾病相关的生物标志物,探讨MXF干预H1N1流感病毒感染可能的作用机制。方法:将30只KM小鼠随机等分为空白组、模型组和MXF组,小鼠滴鼻感染H1N1流感病毒后灌服MXF(给药剂量20 m L·kg~(-1)),模型组和空白组灌服等量水,连续给药7 d并测量各组小鼠的体重和肛温,收集各组小鼠的粪便。采用Halo C_(18)色谱柱(2.1 mm×100 mm,2.7μm),流动相0.05%甲酸水溶液-0.05%甲酸乙腈溶液梯度洗脱,质谱扫描范围m/z 80~1 200,对粪便样品进行LC-MS测定并结合主成分分析和偏最小二乘判别分析寻找潜在生物标志物。结果:空白组、模型组和MXF组代谢模式显著不同,鉴定出了9个潜在生物标志物,分别为磷脂酰乙醇胺、磷脂酰丝氨酸、磷脂酰胆碱、溶血磷脂酰胆碱、吡哆醛、草酰乙酸、琥珀酸、褪黑素和L-犬尿氨酸。结论:MXF干预H1N1流感病毒感染的机制可能与其对色氨酸代谢、维生素B6代谢、甘油磷脂代谢和三羧酸循环等代谢紊乱的回调作用有一定相关性。     

扶正除疫颗粒对感染流感病毒小鼠的保护作用

目的观察扶正除疫颗粒对流感病毒小鼠的影响及体外抑菌、抗病毒作用。方法比较小鼠感染流感病毒的各组死亡率;观察体外抑菌作用;以Hep-2传代细胞株进行传代培养,观察扶正除疫颗粒最大无毒剂量T(D0)、细胞半数感染量(TCID50)以及不同剂量受试药物对感染病毒细胞的保护作用。结果扶正除疫颗粒组感染病毒动物死亡率低于阴性对照组;对多种细菌具有体外抑菌作用,对肺炎链球菌抑菌作用较明显;对病毒所致的细胞病变有一定减轻作用。结论扶正除疫颗粒对感染病毒动物有一定保护作用,还具有抑菌、抗病毒作用。     

四君子汤复方多糖对脾虚小鼠血清代谢组学的影响

目的 :探讨四君子汤复方多糖对脾虚小鼠血清代谢组学的影响。方法 :运用液-质联用(LC-MS)技术采集血清中内源性物质数据,用偏最小二乘判别分析(PLS-DA)方法对试验数据进行分析,寻找四君子汤复方多糖干预的脾虚小鼠血清内源性标记物,阐述其作用机制。结果:PLS-DA得分图中四君子汤复方多糖治疗组与脾虚模型组分离良好,多糖组内源性标记物含量有向正常组靠近的趋势,表明四君子汤复方多糖对脾虚小鼠有一定的改善作用。结论:通过代谢组学技术,确定了四君子汤多糖干预脾虚小鼠的内源性标记物,这些潜在的标记物代谢通路有待于进一步研究。     

石荠苧总黄酮治疗流感病毒性肺炎小鼠的实验研究

目的 观察石荠苧总黄酮对甲型H1N1流感病毒PR8株感染小鼠肺炎的影响.方法 滴鼻感染小鼠建立流感病毒性肺炎模型,采用预防性给药,以利巴韦林为阳性对照,观察给药后各组对小鼠死亡率、生存时间、肺指数的影响.结果 石荠苧总黄酮给药后能明显降低流感病毒PR8株感染后小鼠的肺指数、减少死亡率并延长生存时间（P＜0.05或0.01）.与阳性组比较,差异无统计学意义（P＞0.05）.结论 石荠苧总黄酮在体内对甲型H1N1流感病毒PR8株感染小鼠造成的病毒性肺炎具有明显的治疗作用.     

清感灵胶囊对流感病毒感染小鼠死亡的保护作用研究

目的：观察清感灵胶囊抗流感病毒作用。方法：小鼠滴鼻感染致死量的流感病毒,通过观察小鼠的成活率来反映药物的抗病毒作用。结果：清感灵胶囊能够提高流感病毒感染小鼠的存活率。结论：清感灵胶囊有一定的抗流感病毒作用。     

瓜蒌甘草颗粒对流感病毒肺炎小鼠保护作用研究

目的观察瓜蒌甘草颗粒对流感病毒肺炎小鼠的影响。方法以小鼠经鼻吸入流感病毒亚洲甲型鼠肺适应株(FM1)复制小鼠病毒性肺炎模型,并用瓜蒌甘草颗粒进行治疗,设置利巴韦林对照组,观察其对病毒肺炎小鼠的死亡率、体重、肺指数及病毒血凝滴度的影响。结果瓜蒌甘草颗粒治疗组较模型组死亡率明显降低,平均生存天数明显延长,体重下降得到明显改善,肺指数和血凝滴度都明显降低。结论以清热化痰、解毒扶正为法的瓜蒌甘草颗粒治疗小鼠流感病毒肺炎疗效肯定。     

痰热清注射液对流感病毒FM1感染小鼠的保护作用

目的研究痰热清注射液对流感病毒亚甲型鼠肺适应株(FM1)感染小鼠的保护作用。方法观察痰热清注射液对流感病毒FM1感染小鼠的死亡保护作用,以及肺指数和肺组织病理形态学变化,同时检测肺组织匀浆中流感病毒血凝滴度。结果痰热清注射液治疗组对流感病毒FM1感染小鼠具有明显的保护作用,死亡保护率与模型组小鼠比较,差异显著(P<0.05);肺组织病理形态学观察发现,痰热清注射液治疗组肺部炎症反应较模型组有显著改善。另外,痰热清注射液对肺组织匀浆中流感病毒血凝滴度具有明显的抑制作用。结论痰热清注射液(4mL/kg)对流感病毒FM1感染小鼠具有明显的保护作用。这种保护作用与痰热清注射液在体内抑制流感病毒增殖、减轻肺部炎症反应有关。     

民族药蔓菁对肺炎链球菌和流感病毒感染小鼠的保护作用

目的:研究民族药蔓菁的在体抗菌、抗病毒作用,进而揭示其治疗"肺燥咳嗽"的机制。方法:按照传统方法制备蔓菁膏,观察其低、中、高3个剂量[剂量分别为250、500、1000 mg(浸膏)·(kg·d)-1]对金黄色葡萄球菌、肺炎链球菌、流感病毒感染致小鼠死亡及肺指数的影响。结果:蔓菁膏3个剂量对金黄色葡萄球菌感染小鼠均没有明显的保护作用,但对小鼠小肠炎性病变具有一定的缓解作用;蔓菁膏3个剂量均可降低肺炎链球菌致小鼠感染死亡率(由90%降至15%~30%),中剂量效果最佳(死亡率为15%);蔓菁膏低、高剂量还能减轻流感病毒性小鼠肺炎的充血水肿实变并降低肺指数,其肺指数抑制率分别为29.23%、28.38%,低剂量效果最佳,中剂量没有明显的作用。结论:蔓菁膏对肺炎链球菌和流感病毒感染小鼠具有保护作用,量效关系不成线性,为其临床应用于治疗"肺燥咳嗽"提供参考。