荔枝核皂苷对地塞米松致胰岛素抵抗糖尿病大鼠血糖血脂的影响

目的研究荔枝核皂苷对地塞米松(DX)致胰岛素抵抗(insulin resistance,IR)大鼠血糖、血脂的影响.方法采用DX诱导IR大鼠模型,观察荔枝核皂苷和罗格列酮对病鼠空腹血糖(FBG)和口服葡萄糖耐量试验(OGTT)后2 h血糖(2hBG)以及给药后2h空腹血清血糖(FSG)、总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白-胆固醇(HDL-C)、低密度脂蛋白-胆固醇(LDL-C)、丙二醛(MDA),以及丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、超氧化物歧化酶(SOD)活性等指标的影响.结果荔枝核皂苷改善DX致IR模型大鼠的IGT,降低OGTT后2h期BG和FSG(P＜0.05);并能显著降低病鼠TC、TG、LDL-C含量(P＜0.05-0.01),显著提高HDL-C含量(P＜0.05);抑制AST、ALT活性(P＜0.05),降低AST/ALT;加强SOD活性和降低MDA的含量(P＜0.01),增强抗氧化能力.结论荔枝核皂苷对DX致IR大鼠有降血糖、调血脂改善肝功能等的作用,显示抗氧化作用.     

玉郎伞提取物对高脂血症大鼠血液流变学的影响

目的 研究玉郎伞(YLS)块根提取物(总黄酮、多糖及其水提物)对食饵性高脂血症大鼠脂质代谢及血液流变学指标的影响.方法 建立食饵性高脂血症大鼠模型,将YLS提取物给予高脂血症大鼠,连续灌胃14 d后,检测各组大鼠脂质水平及全血黏度(WBV)、血浆黏度(PV)、全血还原黏度(RV)、红细胞压积(HCT)等8项血流变学指标.结果 与高脂模型组比较,各用药组TC、TG、LDL-C、apoB、AI水平降低;apoA1、HDL-C、apoA1/apoB水平显著性升高(P＜0.01或P＜0.05);各给药组8项血液流变学指标显著降低(P＜0.01或P＜0.05),YLS总黄酮高、低剂量组效果最明显.结论 YLS提取物对高脂血症大鼠的脂质代谢紊乱有显著的调节作用,对防治高脂血症和改善血液流变学有积极的意义.     

新疆传统发酵乳酪乳清对高脂血症大鼠调血脂作用机制的研究

目的：探讨新疆哈萨克族传统发酵乳酪乳清（简称乳酪乳清）调节血脂的作用机制。方法：高脂乳剂灌胃制备高脂血症大鼠模型,以普伐他汀（20 mg?kg-1）作为阳性对照,观察乳酪乳清(50,100 mg?kg-1）对大鼠血清中胆固醇（TC）、三酰甘油（TG）、高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）和一氧化氮（NO）水平以及羟自由基（?OH）的清除能力和血浆胆固醇卵磷脂酰基转移酶（LCAT）活性的影响。结果：与高脂模型组相比,高、低剂量乳酪乳清组均可显著降低高脂血症大鼠血清中TC,TG,LDL-C,HDL-C的水平（均为P＜0.01）,增加NO含量（P＜0.05）,增强?OH的清除能力（P＜0.01）,提高LCAT的活性（P＜0.01）。结论：乳酪乳清可调节血脂水平,其机制可能与其升高HDL-C水平、增强胆固醇卵磷脂酰基转移酶酶活性以及清除?OH有关。     

泻心汤对实验性高脂血症大鼠的影响

目的探讨泻心汤防治高脂血症的作用机制。方法采用高脂饲料制作高脂血症大鼠模型,并以生理盐水、阳性对照药血脂康作对照,观察其对大鼠血脂等的影响。结果泻心汤能降低高脂血症大鼠TC、LDL-C水平,升高HDL-C水平,以中、高剂量组为显著(P<0.05)。结论泻心汤能降低TC、LDL-C,升高HDL-C水平。本研究表明泻心汤能有效调节实验性高脂血症,值得进一步开发研究。     

多廿醇降胆固醇及抗氧化作用的实验研究

目的 观察多廿醇对高脂血症大鼠的降胆固醇和抗氧化作用.方法 将大鼠随机分为正常对照组、多廿醇预防组和高脂造模组.多廿醇预防组喂饲高脂饲料的同时给予多廿醇灌胃10周;高脂造模组先给予高脂饲料4周制备大鼠高脂血症模型,再按照总胆固醇水平分为多廿醇低、中、高剂量组和阳性药物洛伐他汀对照组,灌胃给予相应药物6周后采血,测定血清中总胆固醇(TC)、甘油三脂(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)水平,并计算LDL-C/HDL-C、TG/HDL-C比值和动脉硬化指数(AI);测定血清中丙二醛(MDA)含量,超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-Px)活性.结果 与高脂模型组比较,多廿醇预防组、多廿醇低、中、高剂量组和阳性对照组大鼠的血清中TC、LDL-C含量显著性下降(P＜0.01);阳性对照组大鼠的血清中TG水平显著性降低(P＜0.05);多廿醇预防组、多廿醇高剂量组和阳性对照组大鼠血清中HDL-C水平显著性升高(P＜0.05);多廿醇预防组,多廿醇低、中、高剂量组和阳性对照组LDL-C/HDL-C比值显著性下降(P＜0.01);AI显著性下降(P＜0.01);血清中MDA含量显著性下降(P＜0.05或P＜0.01);多廿醇中、高剂最组和阳性对照组的血清中SOD活性显著性升高(P＜0.05或P＜0.01);多廿醇中和高剂量组的血清中GSH-Px活性显著性升高(P＜0.01).结论 多廿醇对高脂血症模型大鼠具有明显降胆固醇的作用,且可增强机体的抗氧化作用.     

田基黄水煎液对高脂血症模型大鼠血脂、免疫功能的影响

目的：观察田基黄水煎液对高脂血症模型大鼠血脂、免疫功能的影响。方法：将48只Wistar雄性大鼠随机分为4组：正常对照组、模型对照组、辛伐他汀组、田基黄水煎液组,建立高脂血症模型,检测各组大鼠血脂、T淋巴细胞亚群的变化。结果：与模型对照组比较,辛伐他汀组、田基黄水煎液组TC、TG、LDL-C、AI含量均有不同程度的降低（P〈0.01或P〈0.05）,HDL-C含量升高（P〈0.05）;田基黄水煎液组CD4＋、CD4＋/CD8＋均显著升高（P〈0.01）,CD8＋降低（P〈0.01）。与辛伐他汀组比较,田基黄水煎液组TC、LDL-C及CD8＋含量降低（P〈0.05）。结论：田基黄水煎液对高脂血症大鼠的血脂、免疫功能有调节作用。     

脑络舒宁胶囊降血脂及抗动脉粥样硬化作用的实验研究

目的:观察脑络舒宁胶囊对动物血脂水平及主动脉粥样硬化斑块形成的药效学作用.方法:选用高脂+丙基硫氧嘧啶+胆酸钠+维生素D3复合法建立大鼠高脂血症动物模型,采用脂肪乳剂灌胃法建立兔动脉粥样硬化模型.分离血清并检测血清总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、载脂蛋白AI(ApoA Ⅰ)、载脂蛋白B100(ApoB100)水平;剖取家兔主动脉,光镜下观察主动脉内壁有无泡沫细胞及纤维斑块形成及动脉粥性硬化(atheroselemsis,AS)病变的形成.结果:脑络舒宁胶囊组大鼠血清TC及LDL-C水平的升高程度明显低于模型组(P＜0.05,P＜0.01);脑络舒宁胶囊组家兔血清TC及LDL-C水平也较模型组低(P＜0.01),主动脉粥样斑块的形成程度较模型组明显减轻(P＜0.01).结论:脑络舒宁胶囊具有降低高脂血症动物血清TC及LDL-C的作用,对家兔动脉粥样硬化的形成也有抑制作用.     

辛伐他汀对高脂血症大鼠脂肪细胞凋亡的影响

目的观察辛伐他汀对高脂血症大鼠脂肪细胞凋亡的影响,探讨辛伐他汀降低血脂的分子生物学机制,为临床应用提供理论和实验依据.方法采用自制高脂饲料制备高脂血症大鼠模型,观察大鼠血脂指标以及脂肪细胞凋亡指数的变化.结果高脂血症组大鼠血清TG、Tch及VLDL-ch含量均显著高于正常对照组(P＜0.01),而辛伐他汀组大鼠血清TG、Tch及VLDL-ch水平较高脂血症组均显著下降(P＜0.01),高脂血症组大鼠血清HDL-ch水平均显著低于正常对照组(P＜0.01),辛伐他汀组大鼠血清HDL-ch较高脂血症组显著增高(P＜.01);且接近正常组水平.高脂血症组大鼠脂肪细胞凋亡指数均显著低于正常对照组(P＜0.01),而辛伐他汀组大鼠脂肪细胞凋亡指数较高脂血症组均显著升高(P＜0.01).结论辛伐他汀降低高脂血症大鼠血脂,促进脂肪细胞凋亡,从而达到治疗作用.     

无患子皂苷对高脂血症大鼠血脂代谢的影响和对血管内皮功能的保护作用

目的 探讨无惠子皂苷对高脂血症大鼠血脂代谢的影响及其血管内皮功能的保护作用.方法 采用高脂饲料喂养建立大鼠高脂血症模型,同时用无患子皂苷水溶液0.486 g/(kg·d)或0.054 g/(kg·d)、辛伐他汀水溶液0.010 8 g/(kg·d)灌胃给药.第30天末从腹主动脉取血测血清甘油三酯(TG)、总胆田醇(TC)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、丙二醛(MDA)、超氧化物歧化酶(SOD)以及检测血浆前列腺素I2(PGI2)和血栓素A2(TXA2)水平.结果 用药30 d后,各给药组血清中TG,TC,LDL-C,MDA和血浆中血栓素B2水平明显低于模型对照组(P＜0.01),SOD和6-酮-前列腺素F1α水平明显低于模型对照组(P＜0.01).结论 无患子皂苷可调节高脂血症模型大鼠血脂水平,并对血浆血栓素B2及6-酮-前列腺素F1α产生一定影响.     

乌药叶对高脂血症模型大鼠血脂指标及肝组织形态学的影响

目的探讨乌药叶对高脂血症大鼠调节血脂及组织形态学的影响。方法将成年雄性高脂大鼠随机分成4组,设乌药叶0.33、0.66和2.00 g/kg·bw 3个剂量组和1个模型对照组,另设1个正常对照组,实验期45 d。结果在实验末期,中、高剂量组大鼠甘油三脂(TG)、总胆固醇(TC)和低密度酯蛋白胆固醇(LDL-C)均明显低于模型对照组,差异有统计学意义(P0.05或P0.01);中、高剂量组大鼠TG和高剂量组大鼠TC、LDL-C与正常对照组比较,均无统计学意义(P0.05);高剂量组大鼠高密度酯蛋白胆固醇(HDL-C)/LDL-C和HDL-C/TC均明显高于模型对照组,差异有统计学意义(P0.05)。高剂量组大鼠脂体比和中、高剂量组大鼠肝重、肝体比均明显低于模型对照组,差异有统计学意义(P0.05或P0.01);随乌药叶剂量增加,大鼠肝损伤和肝细胞肿胀、变性等病变程度明显减轻,且越靠近肝中央静脉效果越好,高剂量组大鼠肝组织病理变化总得分明显低于模型对照组,差异有统计学意义(P0.01)。模型对照组大鼠在实验末期TG明显低于实验前(P0.05);正常对照组大鼠在实验30 d、45 d TC、HDL-C、HDL-C/TC均明显低于实验前(P0.05或P0.01)。结论乌药叶具有明显促进高脂饮食大鼠TG、TC和LDL-C降低的作用;能明显拮抗高脂饮食大鼠HDL-C/LDL-C和HDL-C/TC降低的作用;明显拮抗高脂饮食大鼠脂体比、肝重、肝体比升高的作用,能明显减轻高脂饮食对大鼠肝的损伤,减轻肝细胞肿胀、变性等病变程度。高脂饮食所致高脂血症大鼠随实验进程TG有一定程度的下降趋势;成年雄性SD大鼠随周龄增长主要是因为其HDL-C下降而导致TC、HDL-C/TC下降。     

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.

---

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.     

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.     

Alzheimer’s disease – current trends in basic and clinical research. Highlights from the 16th ECNP

Advances in the molecular biological knowledge of neuronal nicotinic acetylcholine receptors (nAChRs) have led to a growing interest by the pharmaceutical industry in the development of novel compounds that selectively modulate nAChR function. The ability of (-)-nicotine, an activator of nAChRs, to enhance attentional aspects of cognition in animals and humans, to exert neuroprotective and anxiolytic-like effects, and presumably to mediate the negative correlation between smoking and Alzheimer's (and Parkinson's) Disease, has focused interest on the potential therapeutic utility of modulators of nAChR function for treatment of some of the deficits associated with these progressive, neurodegenerative conditions. Numerous compounds are known which activate nAChRs and which might serve as lead compounds toward the development of such agents. The pharmacologic diversity of neuronal nAChR subtypes suggests the possibility of developing selective compounds which would have more favourable side-effect profiles than existing agents. This broader class of agents, collectively called cholinergic channel modulators (ChCMs), is anticipated to encompass compounds which would have more favourable side-effect profiles than existing agents, which generally exhibit low selectivity. This selectivity may be achieved by preferentially activating some subtypes of nAChRs (i.e., Cholinergic Channel Activators, ChCAs) or inhibiting the function of other subtypes (Cholinergic Channel Inhibitors, ChCIs). An overview of the biology of nAChRs and the rationale for the use of ChCMs for the treatment of dementia related to neurodegenerative diseases are presented, followed by a discussion of lead compounds and compounds under consideration for clinical evaluation.     

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.