磷酸肌酸钠对小鼠阿霉素心肌损伤的保护机制初探

目的:探讨磷酸肌酸钠对小鼠阿霉素心肌损伤的保护作用。方法:雌性BALB/C小鼠60只,建立阿霉素心肌病模型,随机分为磷酸肌酸钠组、阿霉素组、正常对照组。观察小鼠的一般情况,血清中心肌酶TnI、N端前脑钠肽(NT-proB-NP)及心肌组织中超氧化物歧化酶(SOD)、丙二醛(MDA)、ATP酶及乳酸脱氢酶(LDH)的变化,心肌组织HE染色病理变化。结果:与阿霉素组比较,磷酸肌酸钠组LDH、MDA明显降低(P<0.05),SOD和ATP酶活力明显升高(P<0.05);血清NT-proBNP及TnI水平降低(P>0.05)。阿霉素组心肌组织出现明显的水肿、变性。结论:磷酸肌酸钠通过减少氧自由基对阿霉素所致的心肌损伤具有保护作用。     

白藜芦醇对小鼠阿霉素性心肌损伤的保护作用及机制

目的研究白藜芦醇(Res)对阿霉素(ADM)诱导的心肌损伤的保护作用及机制。方法一次性腹腔注射ADM(15mg·kg-1),建立小鼠阿霉素急性心肌损伤模型,并观察白藜芦醇预防性给药的保护作用。结果与正常对照组相比,ADM可使小鼠心电图QRS波电压幅度下降(P<0.01),心律失常率发生达60%;心肌超微结构损伤明显;血清中MDA、NO含量及LDH活性升高,SOD活性降低;p53蛋白表达升高(P<0.01)。与ADM损伤组相比,5、10、15mg·kg-1白藜芦醇呈剂量依赖性降低血清LDH活性和MDA、NO含量,增加SOD活性;减少QRS波电压下降幅度和心律失常发生率;下调p53蛋白表达(P<0.01或P<0.05);减轻电镜下心肌超微结构损伤。白藜芦醇对正常小鼠仅升高SOD活性,对其余指标无明显影响。结论Res对阿霉素性心脏损伤具有保护作用,其机制可能与其增强心肌SOD活力、抗脂质过氧化和抑制心肌细胞凋亡有关。     

大蒜多糖对阿霉素所致小鼠心脏毒性的拮抗作用

目的　研究大蒜多糖 (GP)对中毒性心肌炎的拮抗作用并探讨其机制。方法　建立小鼠阿霉素 (ADR)中毒性心肌炎模型,测定血清、心肌多项生化指标,并观察心肌结构变化。结果　ADR(3mg·kg-1ip, qod×7)可致小鼠血清肌酸激酶(CK)、乳酸脱氢酶(LDH)、谷草转氨酶(GOT)和诱导型一氧化氮合酶(iNOS)活力升高(P<0 01),同时心肌超氧化物歧化酶(SOD)活力下降而丙二醛 (MDA)含量升高 (P<0 01),线粒体水肿明显。GP( 0 75 ~3 0g·kg-1 ig, qd×15)能逆转ADR所致的上述改变,表现为剂量相关性降低血清CK、LDH、GOT和iNOS活力,增加心肌SOD活力和降低MDA含量,尤其以GP大剂量组作用明显 (P<0 05或P<0 01)。光镜和电镜结果也证实了GP的保护作用。结论　GP能拮抗阿霉素所致的小鼠中毒性心肌炎,其作用机制与增强心肌SOD活力和抗心肌脂质过氧化有关。     

舒心片对心肌缺血损伤模型保护作用的实验研究

目的 观察舒心片对心肌缺血损伤模型的保护作用。方法 以心肌缺血损伤模型大鼠为研究对象，观察舒心片对大鼠心电图（ECG）．对血清磷酸肌酸激酶（CK）、乳酸脱氢酶（LDH）、心肌超氧化物歧化酶（SOD）、丙二醛（MDA）含量和对心肌梗塞面积（MIS）等指标的影响。结果 舒心片能明显改善大鼠心肌缺血程度（∑-ST），减小心肌梗塞面积，降低心肌缺血损伤动物的CK，LDH，MDA含量，升高SOD含量。结论 舒心片对心肌缺血损伤有一定的保护作用。     

木犀草苷对阿霉素诱导乳鼠心肌细胞损伤的保护作用

目的观察木犀草苷(luteoloside)对阿霉素(adriamy-cin,ADR)诱导大鼠乳鼠心肌细胞损伤的保护作用,并初步探讨其作用机制。方法采用新生SD大鼠乳鼠,差数分离提取心肌细胞,建立ADR心肌细胞损伤模型,培养48 h后随机分为正常对照组、ADR模型组、木犀草苷与ADR同时给药(12.5、6.25和3.125 mg.L-1)各剂量组及木犀草苷预孵育4 h后,与ADR同时给药(12.5、6.25、3.125 mg.L-1)各剂量组。观察木犀草苷对ADR诱导心肌细胞损伤的量效、时效关系,采用MTT法检测细胞活力、试剂盒检测乳酸脱氢酶(LDH)漏出量、丙二醛(MDA)含量及超氧化物歧化酶(SOD)活力。结果与正常对照组相比,模型组细胞存活率降低、细胞内LDH含量降低,漏出量增加、SOD活性降低及细胞上清液中MDA含量增多。与模型组相比,木犀草苷各处理组心肌细胞存活率均明显增加(P<0.05);木犀草苷与ADR同时给药12.5、6.25 mg.L-1组(P<0.05)能明显降低LDH漏出量、增强SOD活力、降低细胞上清中MDA含量;预孵育4 h后,与ADR同时给药各剂量组均能明显降低LDH漏出量(P<0.05)、增强SOD活力、降低MDA含量(P<0.01)。结论木犀草苷对ADR所致的心肌损伤有明显保护作用;且预孵育4 h后对心肌细胞的保护作用优于未孵育组,其初步作用机制可能与抗自由基、减轻脂质过氧化作用有关。     

PNU282987对异丙肾上腺素所致小鼠心脏重塑的保护作用

目的通过建立异丙肾上腺素所致小鼠心脏重塑模型,观察PNU282987保护心脏的作用。方法连续7 d皮下注射异丙肾上腺素(ISO),诱导小鼠心脏重塑模型,同时腹腔给予PNU282987,检测小鼠心脏重量指数、血清乳酸脱氢酶(LDH)和肌酸激酶(CK)的活性,观察心肌病理形态学的改变;检测心肌组织中超氧化物歧化酶(SOD)和丙二醛(MDA)的含量,通过Western blot测定诱导型一氧化氮合酶(iNOS)的表达。结果与正常对照组相比,异丙肾上腺素组心脏重量指数增加,血清LDH和CK水平显著升高,心肌SOD活性下降,MDA含量增加,心肌组织中iNOS蛋白表达增加;与模型组比较,PNU282987可显著降低心脏重量指数、血清LDH和CK水平,增加心肌SOD活性,降低心肌MDA含量,下调iNOS表达。结论 PNU282987可能通过清除氧自由基,降低iNOS的表达,保护异丙肾上腺素导致的小鼠心脏重塑。     

伤肌宁胶囊含药血清对阿霉素所致心肌细胞损伤的保护作用研究

目的:研究伤肌宁胶囊含药血清对阿霉素(ADR)所致心肌细胞损伤的保护作用。方法:以SD乳鼠心肌细胞做原代培养,复制ADR损伤心肌细胞模型,测定培养上清液中多项生化指标,并运用流式细胞仪检测凋亡细胞。结果:ADR(终浓度为10-6mol·L-1)可致上清液乳酸脱氢酶(LDH)释放量增加,同时细胞超氧化物歧化酶(SOD)活力下降而丙二醛(MDA)含量升高;高、中、低剂量伤肌宁胶囊均可降低LDH活力,增加细胞SOD活力和降低MDA含量。流式细胞仪检测伤肌宁胶囊能降低心肌细胞凋亡率。结论:伤肌宁胶囊能够拮抗ADR引起的心肌细胞自由基脂质过氧化,抑制心肌细胞的凋亡,具有保护心肌细胞损伤的作用。     

马齿苋总黄酮对垂体后叶素诱发小鼠急性心肌缺血的保护作用

目的 观察马齿苋总黄酮(POTF)对垂体后叶素(Pit)诱发小鼠急性心肌缺血的影响.方法 ip Pit予小鼠,建立急性心肌缺血模型,记录小鼠标准Ⅱ导联心电图(ECG)的变化,观察小鼠存活时间、心肌指数(MI)、心肌组织中超氧化物歧化酶(SOD)、丙二醛(MDA)、Ca2+及血清中肌酸激酶(CK)、乳酸脱氢酶(LDH)、MDA的变化.结果 POTF能提高小鼠耐急性缺氧的能力、对HT诱发小鼠Ⅱ导联ECG异常有明显改善,同时升高心肌组织中SOD的活性,降低MDA、Ca2+的含量及降低血清中CK、LDH的水平,心脏重量指数显示POTF对心功能也有明显的改善作用.结论 POTF能保护Pit诱发的小鼠急性心肌缺血损伤,其作用机制可能与降低心肌细胞内钙离子浓度、抑制脂质过氧化有关.     

槲皮素对阿霉素致小鼠心肌损伤的保护作用及其机制

观察槲皮素对阿霉素致小鼠心肌损伤的保护作用并初步探讨其机制。腹腔注射阿霉素(20 mg·kg^-1)复制小鼠心肌损伤模型，检测心电图、心肌超微结构，血清NO含量和iNOS活性，心肌组织LDH、SOD、MDA的水平和p53蛋白表达。并观察槲皮素(50，100及200 mg·kg^-1)对上述指标的影响。阿霉素可导致小鼠心律失常和心肌超微结构损伤；使NO、iNOS、MDA和LDH的水平升高，SOD的水平降低；p53蛋白表达增强。槲皮素(50，100及200 mg·kg^-1)可拮抗阿霉素所致的上述变化。槲皮素对阿霉素性小鼠心肌损伤具有保护作用，其机制与增强SOD活力、降低iNOS活性、抑制p53蛋白表达等有关。     

蜂胶对阿霉素致心肌损伤小鼠的影响

目的 探讨蜂胶对阿霉素致小鼠心肌损伤的干预作用.方法 将32只健康昆明小鼠完全随机分为4组,各8只.优选β2环糊精包合蜂胶的最佳工艺,以该蜂胶环糊精包合物为实验药物建立小鼠阿霉素心肌损伤模型,测定血清、心肌的生化指标,并观察心肌结构变化.结果 阿霉素可致小鼠血清肌酸激酶(CK)、乳酸脱氢酶(LDH)活力升高[阿霉素损伤组比正常对照组分别为(4900±270)U/L比(2970±230)U/L与(1080±213)U/L比(835±79)U/L],同时心肌超氧化物化酶(SOD)活力下降[(266±15)U/L比(427±12)U/L](均P＜0.01).蜂胶各组CK、LDH活力较阿霉素损伤组明显降低,SOD活力明显升高,其中以蜂胶大剂量组作用明显.结论 蜂胶能够拈抗阿霉素引起的自由基脂质过氧化,从而保护心肌细胞.

Abstract：

Objective To establish myocardial injury in mice model through Adriamycin and to observe the preventive effects of the propolis on adriamycin induced myocardial injury in mice. Methods To establish myocardial injury in mice model through β2 cyclodextrin optimum propolis and experimental drugs of Propolis cyclodextrin and to mensurate many biochemistry targets of blood serum and cardiac muscle, observing the change of Cardiac muscle structure. Results ADR may make creatine kinase(CK), lactic dehydrogenase (LDH) of mice blood serum high and make SOD of cardiac muscle low. Propolis can reverse the ADR result of this change. The performance is to reduce the CK and LDH of blood serum and raise the SOD of cardiac muscle by dosage relevance. The effect of big group is obvious ( P＜0.01).Light microscopy also confirmed the protective effect of propolis. Conclusion Propolis can antagonize the free radical lipid peroxidation caused by ADR, protecting myocardial cells.     

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.