油茶皂苷抗心肌缺血大鼠氧自由基和脂质过氧化作用

目的　以皮下注射异丙肾上腺素 (ISO)诱发大鼠心肌损伤为模型 ,观察油茶皂苷 (SQS)对心肌线粒体MDA含量、SOD、GSH Px活性的影响。方法　实验分生理盐水组 (NS组 )、ISO诱发损伤组 (I/R组 )、SQSⅠ组 (I/R +SQS 0 1mg·kg-1)和SQSⅡ组 (I/R +SQS 0 2mg·kg-1)。从阴茎静脉注射各被试药物或NS ,每天 1次 ,连续 3d。末次给药后取心肌组织行上述指标的测定。结果　I/R组MDA含量明显升高、SOD及GSH Px活性显著降低 ;SQS能对抗ISO所致上述指标的改变 ,且呈剂量依赖关系。结论　SQS具有抗ISO所致大鼠心肌缺血时氧自由基和脂质过氧化作用     

人参皂甙药理预适应对束缚应激自发性高血压大鼠心肌缺血再灌注损伤的保护作用

目的：研究人参总皂甙GS和单体Rb1、Rg1对心理应激自发性高血压大鼠（SHR）心肌缺血再灌注损伤（I／R）的保护作用和机制。方法：利用在体心脏缺血再灌注技术，观察GS、Rg1、Rb1预适应对束缚应激SHR大鼠心肌I／R损伤的保护作用。将动物分为SHR组、假手术组、I／R模型组，Gs和Rb1、Rg1大小剂量组和阳性对照（Ena）组，     

雷米普利对实验性糖尿病大鼠缺血／再灌注损伤心肌的保护作用

目的：研究雷米普利（RAM）对糖尿病大鼠心肌缺血／再灌注损伤的保护作用。方法：链脲佐菌素致糖尿病大鼠被随机分为缺血／再灌注（I／R）、缺血预适应（IPC）和RAM三组。RAM组每天用RAM（1mg·kg^-1）灌胃,IPC和I／R组用等体积生理盐水灌胃。4wk后各组动物均经历心肌缺血／再灌注损伤,IPC组于缺血前行心肌缺血预适应。连续监测心电图,检测心肌梗死范围、心肌细胞凋亡、凋亡蛋白Bcl-2与Bax表达,光镜及电镜下观察心肌形态学改变。结果：与I／R组比较,RAM及IPC组室早出现时间明显推迟（14．8±7．8min,11．6±6．0min vs5．5±2．imin．P〈0．05）.     

复方丹参滴丸对心肌保护作用的实验研究

为探讨复方丹参滴丸（DSP）对心肌损伤的保护作用机制，将120只大鼠随机分为4组：异丙肾上腺素（ISO）损伤组、DSP保护组、DSP＋ISO组及正常对照组。应用ISO腹腔内注射造成心肌缺血损伤，测定大鼠血清及心肌组织中脂质过氧化物丙二醛（MDA）含量、超氧化物歧化酶（SOD）活性及血浆中内皮素（ET）和血清中一氧化氮（NO）含量的变化。结果表明，DSP保护组血浆中NO含量升高，与正常对照组差异有显性；DSP保护组注射ISO后MDA、SOD、ET及NO变化程度明显小于单纯ISO组，差异有显性。结论：复方丹参滴丸具有良好的抗急性心肌缺血损伤作用，其作用机制与抗自由基及血管内皮保护效应密切相关。     

无创性延迟肢体缺血预适应保护糖尿病大鼠缺血／再灌注心肌

目的：研究无创性肢体缺血预适应（NDLIP）对糖尿病（DM）大鼠心肌缺血／再灌注（I／R）损伤的影响。方法：大鼠经尾静脉一次性注射链脲佐菌素（STZ）造成急性DM模型后,被随机分为I／R、心脏缺血预适应（CIP）和NDLIP三组。NDLIP组连续3d经历左后肢缺血预适应。第4天,各组动物均经历I／R损伤,CIP组于缺血前行心肌缺血预适应。连续监测血压和心电图变化,观察NDLIP对DM大鼠I／R损伤后心肌电生理功能、心肌梗死范围和心肌酶学的影响,并测定心肌组织中超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH—Px）活性及丙二醛（MDA）含量。结果：成模动物表现出血糖明显升高,体重下降（P〈0．01）。与I／R组比较,NDLIP及CIP组ST一段抬高幅度降低,室早和室速出现时间推迟,持续时间缩短,室性心律失常发生率降低（P〈0．05）,心肌梗死范围缩小（P〈0．01）,心肌细胞乳酸脱氢酶（LDH）、肌酸激酶（CK）及其同工酶（CK—MB）的释放减少（P〈0．05,P〈0．01）,心肌SOD、GSH—Px活性升高（P〈0．01）,MDA含量减少（P〈0．05,P〈0．01）。结论：NDLIP可减轻DM大鼠I／R后心肌细胞损伤,从而减少心肌酶漏出、改善心脏生理功能,具有与CIP程度相当的心脏保护作用,其机制与调节心肌氧化．抗氧化系统功能平衡有关。     

雷米普利对糖尿病大鼠心脏的药理性预适应作用

目的：评价雷米普利对糖尿病大鼠心脏的药理性预适应作用。材料和方法：大鼠尾静脉注射链脲菌素（45mg／kg）制备糖尿病模型。随机分为4组：缺血／再灌注（I／R）组，缺血预适应（IP）组，雷米普利（RAM）药理性预适应组，雷米普利＋缺血预适应（RAM＋IP）组。RAM组及RAM＋IP组每天用雷米普利（1mg／kg）灌胃，共4周。4周后全部大鼠行心肌30min缺血继之2h再灌注，IP组及RAM＋IP组于30min缺血前行心肌缺血预适应。连续监测ST-段变化以及缺血期室性心律失常发生情况，TTC染色测定心肌梗死范围，TUNEL法检测心肌细胞凋亡，免疫组化法测定Bcl-2与Bax的表达，光、电镜下观察心肌形态学改变。结果：与I／R组比较，IP及RAM组均见缺血心脏ST-段抬高幅度显著降低（P〈0．05），室早出现时间推迟（P〈0．05），持续时间缩短（P〈0．05），室速、室颤发生率降低（P〈0．05），心肌梗死范围缩小（P〈0．01），心肌细胞凋亡减轻（P〈0．001），Bcl-2／Bax比值升高（P〈0．05），形态学观察见心肌损伤减轻；RAM＋IP组可见室早持续时间缩短（P〈0．05），室速、室颤发生率降低（P〈0．05），心肌梗死范围缩小（P〈0．01），心肌细胞凋亡减轻（P〈0．001），Bcl-2／Bax比值升高（P〈0．05）。与IP组比较，RAM＋IP组上述各指标无明显差异。结论：IP对患糖尿病4周的大鼠具有心脏保护效应，长期服用RAM对糖尿病心肌具有药物预适应作用，均可增强糖尿病大鼠心脏对缺血／再灌注损伤的耐受性，但二者联用无协同效应。     

硝酸异山梨酯对大鼠心肌后期预适应的诱导作用

目的：探讨硝酸异山梨酯（ISDN）能否诱导大鼠后期预适应及其可能机制。方法：采用大鼠在体缺血再灌注（I／R）模型，将动物随机分为生理盐水组、ISDN给药组、假手术组、后期缺血预适应组、生理盐水＋I，R组、ISDN＋I，R组、生理盐水＋格列苯脲＋I／R组、ISDN＋格列苯脲＋I／R组。前两组于给药24h后，测定心肌组织中的SOD和诱导型一氧化氮合成酶的含量，含I／R组于给药24h后进行缺血40min再灌注1．5h后测心肌梗死范围、心肌组织及血清学指标。结果：ISDN组心肌组织中诱导型一氧化氮合成酶浓度昵显比生理盐水组高（P〈0．01）；后期缺血预适应组和ISDN＋I／R组与生理盐水＋I/R组相比，心肌梗死面积、血清肌酸激酶和乳酸脱氢酶含量明显减少（前两者P〈0．05，后者P〈0．01），心肌组织中NO和锰-SOD显著增加，丙二醛显著下降（P〈0．05）。结论：ISDN能诱导心肌后期预适应，其机制与NO和诱导型一氧化氮合成酶的升高以及机体的抗氧化能力增强有关。     

Netrin-1对活体大鼠心肌缺血再灌注损伤影响的实验研究

目的：研究Netrin-1对活体大鼠心肌缺血再灌注损伤（Ischemia reperfusion injury,I/R）的影响及机制。为临床上提供体外循环（Cardiopulmonary bypass,CPB）下心肌保护新的策略。方法雄性Spraghe-Dawley（SD）大鼠20只,体重450-500g,随机分成2组,体外循环预充液中添加Netrin-1（10只）[I/R＋Netrin-1组],体外循环预充液中不添加Netrin-1（10只）[I/R组]。建立无血预充大鼠深低温停循环（Deep hypothermic circulatory arrest,DHCA）的心肌缺血再灌注的模型。实验结束2h后处死大鼠留取心脏标本。在CPB前、CPB75min （复温后15min）,CPB后2h留取大鼠动脉血测定心肌损伤指标[心肌肌钙蛋白I （cTn I）和心型脂肪酸结合蛋白（HFABP）]。实验结束取大鼠心脏标本用TUNEL法检测心肌细胞凋亡;用Western-blot法测定局部心肌组织直肠癌结肠癌缺失基因（Delete in colorectal carcinoma gene,DCC）蛋白指标。大体光镜下观察心脏组织病理形态学改变;大鼠CPB 前、CPB 15min、CPB 45min （停循环15min）以及 CPB 90min （复温30min）监测血气分析。结果 I/R＋Netrin-1组较I/R组：血清中心肌肌钙蛋白I（cTn I）和心型脂肪酸结合蛋白（HFABP）含量明显减少;心肌缺血再灌注后心肌凋亡明显减少27.5%（P〈0.05）;DCC表达增加（P〈0.05）。HE染色镜下观察发现I/R＋Netrin-1组心肌细胞损伤程度明显减轻。结论Netrin-1对心肌缺血再灌注损伤有保护作用,其机制可能与DCC有关。     

无创性肢体缺血预适应对大鼠心脏的延迟保护作用

目的：研究无创性肢体缺血预适应（RIP）对大鼠缺血再灌后心脏损伤的影响。方法：通过连续3d每天1次3个循环下肢无创性缺血5min再灌5min建立RIP模型。实验分4组：假手术组；缺血再灌（I／R）组；心肌缺血预适应（CIP）组；RIP组。观察RIP对24h后I／R后心脏生理学、室性心律失常的出现时间和持续时间的影响以及其对I／R后梗死面积和形态学改变的影响。结果：与假手术组比较，I／R组ST段明显抬高（P〈0．01），并且有室性心律失常、梗死的出现，心肌细胞的肿胀、炎性细胞的浸润等表现。而CIP和RIP能明显改善模型组受损心肌的状态，减少心肌耗氧量，降低ST段的抬高幅度，推迟室性心律失常出现的时间，缩短持续时间，降低心律失常的发生率，减少心肌梗死面积（P〈0．01），并能减少心肌细胞的肿胀、间质出血和炎性细胞的浸润。结论：RIP对大鼠心肌损伤具有较好的延迟保护作用。     

无创性延迟肢体缺血预适应对大鼠脑缺血再灌注皮层的保护作用

目的：研究无创性延迟肢体缺血预适应（NDLIP）对大鼠脑缺血再灌注损伤的保护作用。方法：通过连续3d,每天1次3个循环左后肢无创性5min缺血、5rain再灌注,建立NDLIP模型。实验分4组：假手术组（sham）、缺血再灌注组（I／R）、早期脑缺血预适应＋I／R组（ECIP＋I／R）、NDLIP＋I／R组。观察其对脑缺血／再灌注的神经缺损症状,脑梗死范围,超氧化物歧化酶（SOD）,谷胱甘肽过氧化物酶（GSH—PX）活力,黄嘌呤氧化酶活力（XOD）,丙二醛（MDA）含量影响。结果：与I/R组相比,ECIP＋I／R组及NDLIP＋I／R组缺血1h,再灌注24h后评分有非常显著的降低;脑梗死范围显著减小。与I／R组比较,ECIP＋I／R组和NDLIP＋I／R组的T-SOD和Mn—SOD活力、GSH—PX活力均升高;XOD活力明显降低,MAD含量明显减少;ECIP＋I／R组和NDLIP＋I／R组间差异无统计学意义。结论：NDLIP可降低I／R对神经的损伤、减小脑梗死范围、提高脑组织抗氧化能力,减少I／R对脑组织的损伤。     

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.     

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.