狗肝菜多糖P2B对CCl4致L-02肝细胞损伤的保护作用

摘 要 目的：探讨狗肝菜多糖（P2B）对四氯化碳(CCl₄)诱导的肝L 02细胞损伤的保护作用。方法: 培养人肝L-02细胞,建立CCl₄肝细胞损伤模型,分组实验：正常对照组、CCl₄损伤组和不同浓度的P2B(0.125、0.25和0.5 mg·ml^-1)样品组。采用MTT法检测生化分析培养液中丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）以及细胞内超氧化物歧化酶（SOD）、丙二醛（MDA）含量。结果: 与CCl₄损伤组相比,各P2B样品组细胞活力明显增强,上清液中ALT、AST活性明显降低;细胞内SOD明显升高、MDA含量降低。结论:P2B对CCl₄诱导的体外L 02肝细胞损伤均具有保护作用,随着浓度的增加,作用也随着增强,其机制可能与其抗氧化作用有关。     

氧化苦参碱对HepG-2与A549细胞增殖抑制与促凋亡活性比较研究

目的 研究氧化苦参碱在体外对人肺癌细胞（A549）、人肝癌细胞（HepG-2）增殖抑制与促凋亡活性,并进行比较。方法 通过MTT比色法和生长曲线法比较氧化苦参碱对两种肿瘤细胞增殖活性的抑制作用,采用HE染色、Hoechst 33258荧光染色和透射电镜3种方法比较氧化苦参碱对两种肿瘤细胞形态的影响及促凋亡作用。结果 MTT结果显示,与对照组比较,氧化苦参碱200、400、800 μg/mL浓度组A549、HepG-2细胞存活率均显著降低（P<0.05、0.01）,半数抑制浓度（IC₅₀）分别为1 055.45、774.11 μg/mL;生长曲线结果显示,与对照组比较,氧化苦参碱组HepG-2细胞培养第4、5天及A549细胞第5天细胞数显著下降（P<0.05、0.01）;在HE染色、Hoechst 33258荧光染色和透射电镜形态学观察实验中,氧化苦参碱对HepG-2细胞作用较明显,细胞数量明显减少,同时出现细胞绒毛减少、细胞核变小变圆、固缩等明显的细胞凋亡形态学特征,对A549细胞形态的影响较弱。结论 氧化苦参碱具有抑制肿瘤细胞增殖和促进凋亡的作用,对HepG-2作用较强,对A549作用较弱,具有一定的特异性。     

枳梖子对实验性肝损伤的防护作用

CCl₄性肝损伤小鼠血清GPT活处、血消和肝MDA含量显著性升高,但血糖和白蛋白浓度显著性下降,表明肝脏结构与功能的严重损伤,用枳子匀浆灌胃14d,然后用CCl₄时,上述指标变化幅度明显变小,提示枳子对CCl₄引起的肝损伤具有防护作用。枳子能显著升高正常小鼠体内SOD活性,降低MDA含量,这种明显的抗脂质过氧化作用,可能是其抗CCl4性肝损伤的代谢机制。     

紫堇灵、乙酰紫堇灵及原鸦片碱对小鼠实验性肝损伤的保护作用

研究了紫堇灵、乙酰紫堇灵及原鸦片碱对小鼠实验性肝损伤的保护作用及其作用机理。小鼠预先分别ig紫堇灵、乙酰紫堇灵或原鸦片碱50及100mg·kg^-12次,对CCl₄、硫代乙酰胺、扑热息痛所致的小鼠肝损伤均有保护作用,使SGPT显著降低,肝病理损伤程度减轻。此3种成分在体外均能抑制CCl₄引起的肝微粒体脂质过氧化及CCl₄转化为CO。在上述实验中乙酰紫堇灵的作用均强于另外两种成分。另外,此3种成分对肝药酶有先抑制后诱导作用。     

低分子量肝素下调转化生长因子转录表达及抗肝纤维化作用

目的观察低分子量肝素钙对肝纤维化动物模型的干预作用及对转化生长因子β1(TGF-β1)表达的影响。方法以四氯化碳(CCl₄)致肝纤维化大鼠为研究对象,观察低分子量肝素的抗肝纤维化作用,同时进一步用酶联免疫吸附法、免疫组织化学法及实时荧光定量RT-PCR法观察低分子量肝素钙治疗动物的血清TGF-β1含量、肝组织原位TGF-β1蛋白表达及mRNA转录水平变化。结果低分子量肝素钙能显著降低CCl4所致实验型肝纤维化大鼠肝纤维化分期(P<0.05);显著降低血清TGF-β1水平、肝组织TGF-β1转录、表达水平(P<0.05)。结论低分子量肝素钙对CCl₄所致的实验大鼠模型有抗肝纤维化作用;机制与抑制TGF-β1转录表达有关。     

灵芝孢子油对大鼠肝纤维化的干预作用

目的 探讨灵芝孢子油对大鼠肝纤维化的影响。方法 选择40% CCl₄皮下注射诱导SD大鼠肝纤维化形成,造模同时用低、中、高剂量（0.33,0.67,2.00 g·kg^-1）灵芝孢子油灌胃干预（每组10只）,观察血浆谷草转氨酶（AST）、谷丙转氨酶（ALT）、丙二醛（MDA）、透明质酸（HA）和肝组织MDA、羟脯氨酸（HyP）等的变化,肝组织HE和Masson染色观察病理变化。结果 灵芝孢子油能显著降低CCl₄所致的肝纤维化大鼠血浆AST、ALT、MDA、HA水平（P<0.05）,降低肝组织HyP、MDA含量（P<0.05）,肝脏病理显示纤维化程度明显减轻（P<0.05）。结论 灵芝孢子油对CCl₄诱导的大鼠肝纤维化具有保护作用。     

甘草类黄酮对四氯化碳致小鼠急性肝损伤的影响

甘草类黄酮(GF)是从甘草根中提得。本文结果表明,预先ig GF 200,400,600mg·kg^-1·d^-1×2d能显著降低CCl₄所致血清谷丙转氨酶,乳酸脱氢酶活性的升高以及肝内丙二醛含量的增加,其作用呈剂量依赖性。GF可减轻CCl₄所致的肝脏坏死,但对血清内酶的活性没有抑制作用,也不减少正常小鼠血清中酶的活性。GF的肝保护作用可能与其抗脂质过氧化作用有关。     

氧化苦参碱对卵巢癌HO8910细胞凋亡影响的血清药理学研究

目的探讨氧化苦参碱体内生物转化及含氧化苦参碱血清对人卵巢癌细胞HO8910的诱导凋亡作用机制。方法采用中药血清药理学实验方法,获得大鼠含氧化苦参碱血清,通过HPLC测定含药血清中氧化苦参碱的生物转化情况,通过MTT法、荧光显微镜、DNA琼脂糖凝胶电泳测定含药血清对人卵巢癌HO8910细胞的诱导凋亡作用,流式细胞术检测含药血清作用后细胞周期时相分布。结果给药大鼠血清中出现保留时间为10.8m in的氧化苦参碱峰图,且血清提取液中氧化苦参碱的浓度为40μg/mL,含氧化苦参碱血清能抑制HO8910细胞生长,经含药血清处理的细胞48h出现典型的细胞凋亡形态学变化和DNA片段的梯形条带,HO8910细胞被阻滞在G₀-G₁期。结论氧化苦参碱经肌注体内生物转化后,血清中的主要代谢成分仍保持不变,含氧化苦参碱血清也具有诱导HO8910细胞凋亡的作用。     

蕊木宁F对小鼠实验性肝损伤的保护作用

蕊木宁(kopsinine)F(K-F)系自云南蕊木提出的一种吲哚类生物碱。该成分对小鼠因注射CCl₄,硫代乙酰胺,TAA及扑热息痛引起的肝损伤有明显的保护作用,使血清谷丙转氨酶降低,肝脏病理损害减轻。该成分对CCl₄引起的肝微粒体脂质过氧化反应和¹⁴CCl₄与肝微粒体进行的共价结合亦有抑制作用。此外,K-F还能提高小鼠的肝微粒体细胞色素P-450活性。以上结果提示蕊木宁F对小鼠实验性肝损害有保护作用。     

二苯乙烯(芪)的一些药理作用

芪(二苯乙烯)通常用于化学工业,对其药理活性的研究很少。通过动物实验我们发现芪能明显保护CCl₄引起的小鼠肝损害,表现在使高的SGPT及SGOT降低、BSP潴留减少、肝组织病变减轻等。芪明显促进肝糖元生成,此作用强度与可的松相近,但芪没有可的松那样的抗炎作用。在去肾上腺小鼠,芪仍能明显促进肝糖元生成,故此作用似乎不通过体内的垂体-肾上腺系统。芪对小鼠戊巴比妥睡眠时间影响不明显。根据实验资料分析,芪对CCl₄肝损害的保护机制大概不是通过酶诱导,也不象某些抗氧化剂那样直接对抗CCl₄的作用,但有可能与其促进肝糖元生成有某种关系。芪有微弱的雌激素作用(约为己烯雌酚的数万分之一)。芪的毒性很低,小鼠一次腹腔注射LD₅₀为6.5 g/kg,灌胃LD₅₀大于8 g/kg,但油溶液毒性较大(灌胃LD₅₀为0.92g/kg)。长期大量给予芪,对雄小鼠的生长及睾丸发育有抑制作用,给狗服芪50 mg/kg/天连续一个月以上未见明显异常反应。     

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.     

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.