促红细胞生成素对心肌缺血再灌注损伤的保护作用

促红细胞生成素(erythropoietin,EPO)是一种酸性含糖量多的蛋白类激素,目前在临床上主要用于治疗各种疾病导致的贫血.但此前有研究发现,EPO还具有显著的心肌保护作用,这种心肌保护效应主要体现在各种组织器官发生缺血再灌注损伤(ischemia reperfusion injury,IRI)时.现就EPO对心肌的保护作用的可能信号转导机制及目前国内外研究进展,作一综述.     

促红细胞生成素对脑缺血再灌注大鼠神经保护作用的研究

<正>研究发现,促红细胞生成素(EPO)作为一种多功能的生长因子,在各种中枢神经系统疾病中具有重要的神经保护作用[1]。外源性EPO通过与其特异性受体结合,对缺血再灌注引起的脑组织损伤发挥神经保护作用,可能与抑制神经细胞凋亡有关。本研究观察了外源性EPO对脑缺血再灌注大鼠的     

促红细胞生成素及其衍生物心肌保护作用的研究进展

近年来研究发现促红细胞生成素(Erythropoietin,EPO)对各种心血管损伤具有心肌保护作用.氨甲酰化促红细胞生成素(carbamylated EPO,CEPO)是EPO的一种衍生物.与EPO相比,CEPO没有促进红细胞生成的能力,仍具有心肌保护功能.EPO和CEPO对心肌保护作用的发现为临床心肌保护的研究提供了新的思路和方法.     

促红细胞生成素预处理通过抗凋亡减轻肠缺血再灌注损伤

目的探讨促红细胞生成素(Erythropoietin,EPO)预处理对大鼠肠缺血再灌注损伤的作用及机制。方法 24只雄性SD大鼠随机分为3组:假手术组(Sham组)、肠缺血再灌注损伤组(IRI组)、促红细胞生成素预处理组(EPO组),每组8只。Sham组、IRI组手术前1 h给予生理盐水(5 000 U/kg,腹腔注射),EPO组缺血前1 h给予促红细胞生成素(5 000 U/kg,腹腔注射),IRI组和EPO组采用血管夹夹闭肠系膜上动脉,置于32℃温箱后45 min后松开血管夹。Sham组操作同上,但不夹闭肠系膜上动脉。再灌注1 h后处死大鼠,收集血清和小肠标本。HE染色后观察小肠病理学形态学变化,采用Western blot检测EPOR、p-EPOR、JAK2、p-JAK2、pSTAT3、STAT3、Bax、Cleavage-caspase3、Bcl-2、Caspase3。结果与Sham组比较,IRI组病理改变及p-EPOR、pJAK2、p-STAT3、Bax、Cleavage-caspase3表达明显增加(P<0.05),Bcl-2、Caspase3表达减少(P<0.05)。与IRI组比较,EPO组病理改变、Cleavage-caspase3蛋白表达减少(P<0.05),p-EPOR、p-JAK2、p-STAT3、Bcl-2、Caspase3表达明显增加(P<0.05)。结论促红细胞生成素预处理可通过诱导JAK2/STAT3信号通路激活而抑制凋亡,减轻肠缺血再灌注损伤。     

促红细胞生成素对机体保护作用的研究进展

促红细胞生成素（Erythropoietin,EPO）是一种相对分子量为34000、受缺氧调节的糖蛋白激素,以往认为主要由肾脏产生,在调节红细胞生成和成熟的过程中具有关键作用,而且发挥多种的旁分泌和自分泌功能。EPO的产生受氧分压的紧密调控,决定其合成主要因素是EPO基因在肝和肾的转录活性,而缺氧诱导因子（Hypoxia—inducible factor,HIF）控制这一过程。近年研究发现,EPO不但可以刺激红细胞的生成,此外还具有保护心、脑、肾组织免遭缺血再灌注损伤的能力。随着研究的深入,EPO的保护效应在各种各样的组织和实验性的缺血诱导的损伤模型中显现。     

促红细胞生成素对大鼠心肌缺血再灌注损伤的保护作用

目的探讨促红细胞生成素（EPO）对大鼠心肌缺血再灌注损伤（MIRI）的保护作用及其作用机制。方法采用结扎左冠状动脉前降支30min,再灌注120min的方法建立大鼠MIRI模型,将45只大鼠随机分为假手术组、MIRI组、EPO组（rHuEPO3000U／kg）。肢体Ⅱ导联心电图记录再灌注心律失常情况,检测血清丙二醛（MDA）、肌酸激酶（CK）、乳酸脱氢酶（LDH）水平。结果MIRI组和EPO组心律失常评分较假手术组明显升高（P〈0．05）;EPO组室性心动过速和心室纤颤的持续时间明显低于MIRI组（P〈0．05）。MIRI组和EPO组血清MDA、CK、LDH水平较假手术组明显升高（P〈0．05）;EPO组明显低于MIRI组（P〈0．05）。结论EPO对心肌MIRI有明显的保护作用,其机制可能与抗氧化应激有关。     

促红细胞生成素和甲泼尼龙对损伤星形胶质细胞增殖的影响

目的研究在促红细胞生成素(erythropoietin,EPO)和甲泼尼龙(Methylprednisolone,MPSS)干预下对损伤星形胶质细胞增殖的影响,探讨EPO和MPSS联合应用在脊髓损伤中的作用。方法取自SD大鼠大脑原代培养星形胶质细胞,缺营养培养3h后分别在促红细胞生成素(erythropoietin,EPO)和甲泼尼龙(erythropoietin,EPO)的培养基中培养24、48小时后,MTT法检测星形胶质细胞增殖活性的变化。结果缺营养可抑制星形胶质细胞增殖,促红细胞生成素和甲泼尼龙对正常细胞增殖无明显影响作用,EPO和MPSS均促进损伤细胞增殖,两者联合减量应用对细胞增殖有明显影响作用。结论 EPO+MPSS(半量组)联合减量应用对星形胶质细胞增殖作用表达的升高作用优于单独应用甲泼尼龙。     

促红细胞生成素对急性心肌缺血再灌注后大鼠心肌凋亡基因表达影响的实验研究

目的：观察促红细胞生成素（ EPO）对急性心肌缺血再灌注心肌凋亡基因表达的影响,探讨EPO的心脏保护机制。方法建立大鼠心肌缺血再灌注模型36只大鼠随机分为假手术组（ Sham组）、缺血再灌注对照组（ IR组）和EPO组（ EPO 3000 U·kg-1· d-1,共3 d）,每组12只。3组48 h、2周缺血边缘区心肌组织Bcl-2、Bax蛋白及血管内皮生长因子（ VEGF）蛋白表达（免疫组化法）,以及相关基因mRNA的变化（ RT-PCR法）。结果与IR组比较,EPO组Bcl-2蛋白表达在48 h、2周、分别增高27 b．7％、31．4％（ P ＜0．01）;Bax 蛋白表达在48 h、2周均降低,分别降低20．9％、18．0％（ P ＜0．01）;Bcl-2/Bax比值在各时间点均显著增高（ P ＜0．05）;EPO组VEGF蛋白表达在48 h、2周均增高,分别增高22．1％、21．4％（ P ＜0．05或＜0．01）。与IR组比较,EPO组Bcl-2/BaxmRNA比值在各时间点均显著增高（ P ＜0．05）。结论 EPO可能通过调节Bcl-2、Bax的表达而减少细胞凋亡,抑制缺血而灌注损伤,产生对心脏的保护作用。     

丹红注射液对沙鼠前脑缺血再灌注后脑组织的神经保护作用

目的 探讨丹红注射液干预后对沙鼠前脑短暂性缺血再灌注的保护作用,及对热休克蛋白20(HSP20)和促红细胞生成素(EPO)表达的影响.方法 将雄性蒙古沙鼠的双侧颈总动脉分离并夹闭10 min后恢复灌注血流建立前脑缺血再灌注模型.按照体重将沙鼠随机分为3组:假手术组,模型组和实验组,每组10只.实验组在造模前1天腹腔注射...     

EPOR在出生后小鼠肾皮质表达的变化

促红细胞生成素(erythropoietin,EPO)作为一种重要的红系分化的细胞因子而存在于体内,近些年来已经被证实是一种可以促进脑和心肌发育的生长因子。EPO主要是由肾皮质中的纤维样细胞产生的。基于此种重要的解剖结构基础以及其在脑和心肌的重要促进生长发育的作用,此项实验主要探讨了EPO是否在肾皮质生长发育中起重要作用。EPO主要通过与促红细胞生成素受体(EPOR)结合而发挥作用。     

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.     

Pharmacological treatment of COVID-19: an opinion paper

The precocity and efficacy of the vaccines developed so far against COVID-19 has been the most significant and saving advance against the pandemic. The development of vaccines has not prevented, during the whole period of the pandemic, the constant search for therapeutic medicines, both among existing drugs with different indications and in the development of new drugs. The Scientific Committee of the COVID-19 of the Illustrious College of Physicians of Madrid wanted to offer an early, simplified and critical approach to these new drugs, to new developments in immunotherapy and to what has been learned from the immune response modulators already known and which have proven effective against the virus, in order to help understand the current situation.     

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.