海地瓜岩藻聚糖硫酸酯抑制慢性低度炎症反应及机制研究

目的 采用胰岛素抵抗模型小鼠研究海地瓜岩藻聚糖硫酸酯(fucoidan from Acaudina molpadioidea,Am-FUC)对慢性低度炎症反应的影响。方法 以高脂高果糖饲料饲喂法建立胰岛素抵抗小鼠模型,灌胃Am-FUC(80mg.kg-1.d-1)90d。实验结束后,检测小鼠空腹血糖、空腹胰岛素水平和血清中肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、C-反应蛋白(C-reactive protein,CRP)、白细胞介素-6(interleukin-6,IL-6)、瘦素(leptin,Lep)、抵抗素(resistin,Res)、游离脂肪酸(free fatty acids,FFA)等促炎因子水平及脂联素(adiponectin,ADP)、白细胞介素-10(interleukin-10,IL-10)等抗炎因子水平;采用q-RT-PCR法检测小鼠肝脏中TNF-α、IL-6、Lep、ADP mRNA表达及NF-κB通路中关键基因IKKβ、IκB-α、NF-κB mRNA表达。结果 Am-FUC可显著降低胰岛素抵抗小鼠空腹血糖和空腹胰岛素水平;显著降低血清中促炎因子分泌及TNF-α、IL-6、Lep mRNA表达,提高抗炎因子分泌及ADP mRNA表达;显著下调NF-κB通路中关键基因NF-κB、IKKβ mRNA表达,上调IκB-α mRNA表达。结论 Am-FUC具有抑制慢性低度炎症反应作用,其作用机制与下调NF-κB信号转导通路有关。     

毛磊,王静凤,陈鹏,张昕,王一名,常耀光,薛长湖*

目的 研究梅花参岩藻聚糖硫酸酯(Fucoidan from Thelenota ananas,Ta-FUC)对高脂高果糖诱导的胰岛素抵抗模型小鼠慢性炎症的改善作用及相关信号通路。 方法 采用高脂高果糖饲喂C57BL/6小鼠,建立胰岛素抵抗模型。雄性C57BL/6小鼠随机分为6组：正常对照组、模型对照组、阳性对照组(RSG,1 mg/(kg.d))、Ta-FUC低剂量组(20 mg/(kg.d))和Ta-FUC高剂量组(80 mg/(kg.d))。连续饲喂13 wk后,检测各组小鼠血糖、胰岛素和炎症因子水平以及炎症信号通路NF-κB中关键基因mRNA的表达。 结果 Ta-FUC能显著降低小鼠体脂比,显著降低空腹血糖和空腹血清胰岛素水平,提高葡萄糖和胰岛素耐受水平。显著降低血清促炎因子FFA、TNF-α、IL-6、抵抗素、瘦素和CRP含量,显著提高血清抗炎因子IL-10和脂联素含量。显著下调NF-κB信号通路关键基因Ikkβ和NF-κB mRNA的表达量,上调NF-κB抑制物I-κBα mRNA的表达量。结论 梅花参岩藻聚糖硫酸酯通过抑制炎症信号通路NF-κB,显著改善胰岛素抵抗模型小鼠的慢性炎症。     

代谢性内毒素血症小鼠胰腺组织炎性递质的表达

目的观察代谢性内毒素毒血症（ME）小鼠胰腺组织脂联素、白细胞介素-6（IL-6）、单核细胞趋化蛋白-1（MCP-1）及其受体CCR2 mRNA的表达,探讨ME对胰腺组织炎性反应和胰岛素抵抗的影响。方法将纯系C57BL／6J雄性小鼠编号按随机数字法分为代谢性内毒素毒血症组6只和对照组6只,代谢性内毒素毒血症组采用皮下微型泵导入微量脂多糖,建立ME动物模型,对照组则每日泵入相应体积的生理盐水。采用实时荧光定量PCR法的相对定量分析（与GAPDH对照）,检测小鼠胰腺组织脂联素、IL-6、MCP-1及其受体CCR2 mRNA的表达。结果代谢性内毒素毒血症组小鼠空腹血糖浓度降低（P〉0．05）;小鼠体重净增值、空腹胰岛素及胰岛素抵抗指数均升高（均P〈0．05）;小鼠胰腺组织中IL-6、MCP-1及CCR2 mRNA的表达均增强（均P〈0．05）,脂联素mRNA的表达明显减低（P〈0．01）。结论代谢性内毒素血症能够增强胰腺组织中促炎因子的表达,减低抗炎因子的表达,促进胰腺组织的炎症反应,降低胰岛素敏感性。     

冰岛刺参岩藻聚糖硫酸酯对胰岛素抵抗小鼠炎症改善作用的研究

目的 研究冰岛刺参岩藻聚糖硫酸酯（fucoidan from the sea cucumber Cucumaria frondosa, Cf-FUC）对胰岛素抵抗小鼠炎症反应的改善作用。方法 以高脂高糖饲料饲喂法建立胰岛素抵抗小鼠模型。雄性C57BL/6J小鼠随机分为正常对照组、模型对照组、阳性对照组、Cf-FUC组。正常对照组饲喂标准饲料,其它组饲喂高脂饲料。阳性对照组、Cf-FUC组分别在饲料中添加罗格列酮（rosiglitazone, RSG, 1 mg?kg?1?d?1）、Cf-FUC (80 mg?kg?1?d?1）。各组小鼠自由摄食摄水19周。实验结束后,检测血清肿瘤坏死因子α（TNF-α）、MIP-1、IL-1β、IL-6和IL-10表达水平,荧光定量PCR方法检测小鼠脂肪组织炎症细胞因子基因mRNA表达水平,Western方法检测JNK1、IKKβ磷酸化蛋白水平及细胞核和细胞质中NFκB蛋白表达量。结果Cf-FUC可显著降低胰岛素抵抗小鼠血清TNF-α、MIP-1、IL-1β和IL-6浓度,增加IL-10浓度;抑制小鼠脂肪组织TNF-α、MIP-1、IL-1β和IL-6基因mRNA表达,促进IL-10基因mRNA表达;抑制JNK1和IKKβ的磷酸化,增加细胞质中NFκB蛋白表达量,减少细胞核中NFκB蛋白表达量。结论Cf-FUC能通过抑制JNK和IKKβ/NFκB信号通路抑制促炎症因子分泌,增加抑炎症因子分泌,改善胰岛素抵抗小鼠的炎症反应。     

海地瓜岩藻糖基化海参硫酸软骨素对Ⅱ型糖尿病小鼠胰岛素抵抗改善作用的研究

目的研究海地瓜岩藻糖基化海参硫酸软骨素(fucosylated chondroitin sulfate from the sea cucumber Acaudina molpadioides,Am-CHS)对Ⅱ型糖尿病小鼠胰岛素抵抗的改善作用。方法以高脂高糖饲料饲喂法建立Ⅱ型糖尿病小鼠模型。雄性C57BL/6小鼠随机分为正常对照组、模型对照组、阳性对照组、实验A、B、C组。正常对照组饲喂标准饲料,其它组饲喂高脂饲料。阳性对照组、实验A、B、C组分别在饲料中添加罗格列酮(rosiglitazone,RSG,1mg·kg-1·d-1)、高剂量Am-CHS(80mg·kg-1·d-1)、低剂量Am-...     

海带海参降糖口服液对2型糖尿病大鼠肝组织中IRS-2及PTP-1BmRNA表达的影响

目的 观察海带海参降糖口服液对2型糖尿病大鼠的影响,检测肝组织中IRS-2及PTP-1BmRNA表达水平,从胰岛素转导的初始环节探讨其作用机制。方法 采用高糖高脂饲料结合链脲佐菌素制备2型糖尿病大鼠模型,观察海带海参降糖口服液对2型糖尿病大鼠空腹血糖值、血清中胰岛素含量的影响、计算胰岛素敏感性及胰岛素抵抗指数,RT-PCR检测肝组织中IRS-2及PTP-1BmRNA表达水平。结果 与模型组相比,海带海参降糖口服液能显著降低动物空腹血糖值、胰岛素抵抗指数以及肝组织中PTP-1BmRNA表达水平,增加血清中胰岛素含量、胰岛素敏感性及肝组织中IRS-2mRNA表达水平。结论 海带海参降糖口服液具有显著的改善作用,可能是通过影响胰岛素转导初始环节,上调肝组织中IRS-2mRNA表达水平以及下调PTP-1BmRNA表达水平得以发挥。     

胰岛素抵抗的炎症机制及治疗研究进展

炎症因素是胰岛素抵抗(IR)的诱因,IR也可诱发炎症。细胞因子肿瘤坏死因子(TNFα-)和白介素(IL)系列能降低机体组织细胞对胰岛素的敏感性,来自脂肪等组织的细胞因子和炎症敏感蛋白如抵抗素、脂联素、C反应蛋白和纤溶酶原激活物抑制剂(PAI-1)等对胰岛素抵抗的发生也有重要作用。抗炎药物能改善胰岛素抵抗的状态。我们就胰岛素抵抗的炎症机制以及治疗展开综述。     

炎症与胰岛素抵抗的相关研究

胰岛素抵抗在2型糖尿病和代谢综合症等疾病中起着重要的作用.在胰岛素抵抗的发生及发展中,大量的炎症因子参与了这一过程,如白介素-6,肿瘤坏死因子-α,C-反应蛋白等.研究炎症因子与胰岛素抵抗的关系以及胰岛素抵抗的分子机制为中药新药研发开辟了新途径.     

胰岛素抵抗的炎症机制及治疗策略

研究证明胰岛素抵抗是一个慢性亚临床炎症过程,细胞因子肿瘤坏死因子(TNF)和白介素(IL)-6都能减低机体组织细胞对胰岛素的敏感性,来自脂肪等组织的细胞因子和炎症敏感蛋白如抵抗素、脂联素、C反应蛋白和纤溶酶原激活物抑制剂(PAI)-1等对胰岛素抵抗的发生也有重要作用.通过对胰岛素抵抗炎症机制的认识,有助于对这些代谢性疾病的发生和发展进行预测、动态观察和干预治疗.     

过氧化物酶体增殖物激活受体β亚型激动剂GW501516对胰岛素抵抗模型小鼠的胰岛素增敏作用(英文)

目的在长期(4个月)高脂高糖饮食诱导的胰岛素抵抗小鼠模型上,评价过氧化物酶体增殖物激活受体β(PPARβ)亚型激动剂GW501516对胰岛素抵抗的改善作用,并对可能的相关机制进行探讨。方法C57BL/6J小鼠采用高脂高糖饮食(35%脂肪,30%麦芽糖)诱导4个月,待产生明显的糖脂代谢紊乱。实验分为正常对照、饮食导致的肥胖(DIO)模型与DIO模型+GW501516(10mg·kg-1·d-1)给药组。隔天监测体重与进食量情况,以葡萄糖氧化酶法检测血糖,并进行口服葡萄糖耐量试验和血脂(甘油三酯、总胆固醇和高密度脂蛋白)含量的检测。以组织学方法检测肝脏异位脂积聚及病理变化情况。为确证其相关作用机制,采用RT-PCR方法检测骨骼肌内PPARβ下游糖脂代谢靶基因的表达。结果GW501516有效改善模型小鼠的胰岛素抵抗,显著降低口服糖耐量曲线下面积〔DIO模型组,(32.4±4.6)mmol·h·L-1, DIO +GW501516组,(23.4±2.5)mmol·h·L-1,n=7 ~8, P<0.05〕,降低空腹血糖,增加血清高密度脂蛋白含量,减轻模型小鼠的肝脂肪变性。此外,RT-PCR结果表明,骨骼肌卡尼汀(肉碱)软脂酰转移酶1b,解偶联蛋白(UCP)2,UCP3明显上调,同时葡萄糖转运蛋白也明显上调。结论GW501516显著改善模型小鼠的胰岛素抵抗,恢复其空腹血糖值,降低肝脏内异位脂积聚,其治疗作用机制可能与①促进骨骼肌内脂肪酸氧化和能量的解偶联,②促进骨骼肌内的糖摄取有关,提示PPARβ可能是胰岛素抵抗及代谢综合征的有效治疗靶标。     

Efficacy of gut lavage,hemodialysis, and hemoperfusion in the therapy of paraquat or diquat intoxication

Clinical and in vitro investigations were carried out to test the efficacy of gut lavage, hemodialysis, and hemoperfusion in the treatment of poisoning with paraquat or diquat. In a patient suffering from diquat intoxication 130 times more diquat was removed by gut lavage 30 h after ingestion than was removed by complete aspiration of the gastric contents.Determination of in vitro clearances for paraquat and diquat by hemodialysis showed that, at serum concentrations of 1–2 ppm, such as are frequently encountered in poisoning in man, toxicologically relevant quantities of herbicide cannot be removed from the body. At a concentration of 20 ppm, on the other hand, hemodialysis proved to be effective, the clearance being 70 ml/min at a blood flow rate of 100 ml/min. The efficacy of hemoperfusion with coated activated charcoal was on the whole better. Especially at concentrations around 1–2 ppm, the clearance values for hemoperfusion were some 5–7 times higher than those for hemodialysis.In a patient suffering from paraquat poisoning, both hemodialysis as well as hemoperfusion were carried out. The in vitro results could be confirmed: At serum concentrations of paraquat less than 1 ppm no clearance could be obtained by hemodialysis while by hemoperfusion with activated charcoal quite high clearance values were measured and the serum level dropped down to zero.

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Zusammenfassung Klinische Untersuchungen und Laboratoriumsversuche wurden durchgeführt, um die Wirksamkeit von Darmspülung, Hämodialyse und Hämoperfusion bei Paraquat- und Deiquat-Vergiftungen zu prüfen.Bei einem Patienten wurde 30 Std nach Deiquat-Aufnahme durch Darmspülung 130mal mehr Deiquat entfernt als durch vollständige Aspiration des Mageninhaltes. In vitro-Versuche ergaben, daß bei Blutserumkonzentrationen von 1–2 ppm, die bei Vergiftungen oft gemessen werden, durch Hämodialyse keine toxikologisch relevanten Paraquat- oder Deiquat-Mengen entfernt werden können. Dagegen erwies sich die Hämodialyse bei 20 ppm und einer Blutumlaufgeschwindigkeit von 100 ml/min mit einer Clearance von 70 ml/min als wirksam. Die Hämoperfusion mit beschicheter Aktivkohle war in diesen Versuchen aber eindeutig überlegen, denn insbesondere bei Konzentrationen um 1–2 ppm waren die Clearance-Werte 5–7mal höher als bei der Hämodialyse.Die in vitro-Ergebnisse wurden bei einem Patienten mit einer Paraquat-Vergiftung bestätigt: Bei Konzentrationen unter 1 ppm war die Hämodialyse wirkungslos, während durch Hämoperfusion relativ hohe Clearance-Werte erreicht wurden, so daß der Serumspiegel rasch unter die Nachweisgrenze abfiel.

     

In vitro studies on sterically stabilized liposomes (SL) as enzyme carriers in organophosphorus (OP) antagonism

This study describes a new approach for organophosphorous (OP) antidotal treatment by encapsulating an OP hydrolyzing enzyme, OPA anhydrolase (OPAA), within sterically stabilized liposomes. The recombinant OPAA enzyme was derived from Alteromonas strain JD6. It has broad substrate specificity to a wide range of OP compounds: DFP and the nerve agents, soman and sarin. Liposomes encapsulating OPAA (SL)* were made by mechanical dispersion method. Hydrolysis of DFP by (SL)* was measured by following an increase of fluoride ion concentration using a fluoride ion selective electrode. OPAA entrapped in the carrier liposomes rapidly hydrolyze DFP, with the rate of DFP hydrolysis directly proportional to the amount of (SL)* added to the solution. Liposomal carriers containing no enzyme did not hydrolyze DFP. The reaction was linear and the rate of hydrolysis was first order in the substrate. This enzyme carrier system serves as a biodegradable protective environment for the recombinant OP-metabolizing enzyme, OPAA, resulting in prolongation of enzymatic concentration in the body. These studies suggest that the protection of OP intoxication can be strikingly enhanced by adding OPAA encapsulated within (SL)* to pralidoxime and atropine.     

Steroidal sapogenin contents in some domestic plants

In order to find out the values of the steroid resources for the future use. the compositions and contents of steroidal sapogenins from 13 domestic plants have been investigated. As a result,Dioscorea nipponica, D. quinqueloba andSmilax china were found to have large amount of diosgenin. And pennogenin inTrillium kamtschaticum andParis verticillata, yuccagenin inAllium fistulosum, hecogenin inAgave americana and neochlorogenin inSolanum nigum were appeared to be major steroidal sapogenins.     

Synthesis,Cytotoxicity and Antileishmanial Activity of Some N-(2-(indol-3-yl)ethyl)-7-chloroquinolin-4-amines

We report herein the condensation of 4,7-dichloroquinoline (1) with tryptamine (2) and D-tryptophan methyl ester (3) . Hydrolysis of the methyl ester adduct (5) yielded the free acid (6) . The compounds were evaluated in vitro for activity against four different species of Leishmania promastigote forms and for cytotoxic activity against Kb and Vero cells. Compound (5) showed good activity against the Leishmania species tested, while all three compounds displayed moderate activity in both Kb and Vero cells.     

Aquatic Insects and Trace Metals: Bioavailability,Bioaccumulation, and Toxicity

Abstract

The uptake of metals from food and water sources by insects is thought to be additive. For a given metal, the proportions taken up from water and food will depend both on the bioavailable concentration of the metal associated with each source and the mechanism and rate by which the metal enters the insect. Attempts to correlate insect trace metal concentrations with the trophic level of insects should be made with a knowledge of the feeding relationships of the individual taxa concerned. Pathways for the uptake of essential metals, such as copper and zinc, exist at the cellular level, and other nonessential metals, such as cadmium, also appear to enter via these routes. Within cells, trace metals can be bound to proteins or stored in granules. The internal distribution of metals among body tissues is very heterogeneous, and distribution patterns tend to be both metal and taxon specific. Trace metals associated with insects can be both bound on the surface of their chitinous exoskeleton and incorporated into body tissues. The quantities of trace meals accumulated by an individual reflect the net balance between the rate of metal influx from both dissolved and particulate sources and the rate of metal efflux from the organism. The toxicity of metals has been demonstrated at all levels of biological organization: cell, tissue, individual, population, and community. Much of the literature pertaining to the toxic effects of metals on aquatic insects is based on laboratory observations and, as such, it is difficult to extrapolate the data to insects in nature. The few experimental studies in nature suggest that trace metal contaminants can affect both the distribution and the abundance of aquatic insects. Insects have a largely unexploited potential as biomonitors of metal contamination in nature. A better understanding of the physico-chemical and biological mechanisms mediating trace metal bioavailability and exchange will facilitate the development of general predictive models relating trace metal concentrations in insects to those in their environment. Such models will facilitate the use of insects as contaminant biomonitors.