高渗氯化钠对失血性休克大鼠小肠黏膜NF-κB的影响

目的:通过高渗氯化钠(hypertonic sodium chloride,HSC)和乳酸林格氏液(RL)复苏失血性休克大鼠,探讨高渗盐对小肠黏膜核因子-Kappa B(NF-κB)的影响.方法:以SD大鼠为实验对象,分别检测休克前、重度休克后以及以HSC和RL复苏后不同时间点小肠黏膜NF-κB表达情况.结果:失血后小肠黏膜内炎症细胞浸润增加,并出现糜烂和溃疡,小肠黏膜内炎症细胞和腺细胞NF-κB的表达也明显增加,给予HSC复苏后,小肠黏膜形态明显改善,表达NF-κB的细胞恢复休克前水平;给予RL复苏后小肠黏膜损伤进一步加重,NF-κB的表达进一步增加.结论:HSC能快速抑制肠道组织中NF-κB的表达,对肠道黏膜具有一定保护作用.     

高渗氯化钠对失血性休克大鼠小肠黏膜NF-κB的影响

目的:通过高渗氯化钠(hypertonic sodium chloride,HSC)和乳酸林格氏液(RL)复苏失血性休克大鼠,探讨高渗盐对小肠黏膜核因子-Kappa B(NF-κB)的影响.方法:以SD大鼠为实验对象,分别检测休克前、重度休克后以及以HSC和RL复苏后不同时间点小肠黏膜NF-κB表达情况.结果:失血后小肠黏膜内炎症细胞浸润增加,并出现糜烂和溃疡,小肠黏膜内炎症细胞和腺细胞NF-κB的表达也明显增加,给予HSC复苏后,小肠黏膜形态明显改善,表达NF-κB的细胞恢复休克前水平;给予RL复苏后小肠黏膜损伤进一步加重,NF-κB的表达进一步增加.结论:HSC能快速抑制肠道组织中NF-κB的表达,对肠道黏膜具有一定保护作用.     

胡黄连苷Ⅱ对大鼠脑缺血/再灌注损伤NF-κB和I-κB的干预作用

目的研究胡黄连苷Ⅱ对大鼠脑缺血/再灌注后核转录因子κB(NF-κB)和NF-κB抑制因子(I-κB)表达的影响。方法应用线栓法建立大鼠大脑中动脉闭塞再灌注模型,经尾静脉注射胡黄连苷Ⅱ(10mg·kg-1)和丹参素钠(10mg·kg-1)干预治疗,原位TUNEL检测神经细胞凋亡,免疫组化检测NF-κB和I-κB的表达,ELISA法检测脑组织匀浆NF-κB和I-κB的含量。结果假手术组大鼠皮质、纹状体和海马区脑组织NF-κB和I-κB弱表达,TUNEL阳性细胞数量较少,散在分布。阴性对照组大鼠各区脑组织TUNEL阳性细胞数量较假手术组均增多,NF-κB和I-κB表达增强,脑组织匀浆NF-κB和I-κB增高(P<0.05)。阳性对照组和胡黄连苷组各区脑组织TUNEL阳性细胞数量,NF-κB和I-κB表达(A值)及脑组织匀浆NF-κB和I-κB含量均低于阴性对照组(P<0.05),阳性对照组与胡黄连苷组比较,各指标差异均无显著性(P>0.05)。结论胡黄连苷Ⅱ可能通过下调NF-κB和I-κB的表达,抑制脑缺血/再灌注损伤的炎症反应导致的神经细胞凋亡。     

葛根素对大鼠颅脑损伤后ICAM-1和NF-κB表达的影响

目的观察葛根素对大鼠颅脑损伤后细胞间黏附分子-1(ICAM-1)和核因子(NF-κB)表达的影响。方法雄性SD大鼠,建立大鼠颅脑损伤模型,随机分组,给予葛根素治疗后,测定脑组织中MDA含量和SOD活性;分别通过Western blot方法,分析组织中ICAM-1和NF-κB蛋白表达的变化。同时利用RT-PCR法,观察脑组织中ICAM-1和NF-κB表达水平的变化。结果大鼠颅脑受到损伤后,脑组织中SOD活性显著降低(P<0.05),MDA含量显著增加(P<0.05),经葛根素预先处理的大鼠,可以显著增加脑组织中SOD的活性,并降低MDA的含量。与假手术组相比,模型组大鼠脑组织中ICAM-1和NF-κB表达显著升高(P<0.05),经葛根素处理组的大鼠,与模型组大鼠相比较,脑组织中ICAM-1和NF-κB mRNA表达显著降低。结论葛根素调节大鼠颅脑损伤后ICAM-1和NF-κB的表达,可能是葛根素保护大鼠颅脑损伤的分子机制。     

胆囊收缩素-8对大鼠急性脑损伤后核因子-κB活性的影响

目的：探讨胆囊收缩素-8（cholecystokinin-8,CCK-8）对实验性大鼠急性脑损伤后核因子-κB（necular factor kappa B,NF-κB）活性的影响。方法取成年 Wistar 大鼠60只,体重280~300 g,随机分为对照组、创伤组与CCK-8组。采用电泳迁移率改变分析方法（electrophoretic mobility shift assay,EMSA）检测核内 NF-κB 的活性,用免疫组化方法观察 NF-κB 在细胞内的表达情况,并用干湿重法测量损伤侧脑组织含水量。结果创伤组各时间点 NF-κB的活性以及脑含水量较假手术组均有明显增高,而 CCK-8组 NF-κB 的活性明显受到抑制,脑水肿也有所减轻。结论急性脑外伤后,脑组织 NF-κB 的表达明显增加,CCK-8可以通过抑制 NF-κB 的活性有效的减轻继发性炎性损害。     

连续4周口服雷公藤甲素对大鼠血红素加氧酶的影响

目的探讨雷公藤甲素(triptolide)灌胃给予SpragueDawley(SD)大鼠4周后对肝脏血红素加氧酶(HO-1)的影响。方法 SD大鼠随机分成4组:对照组,雷公藤甲素(45、90、180μg·kg-1)组。灌胃给药,每天1次,连续4周。末次给药后隔天取材,采用实时定量PCR检测肝脏组织中HO-1基因的mRNA表达水平,Western blot检测肝脏中HO-1的表达量和NF-κB的转位入核情况。结果给予雷公藤甲素4周后,大鼠肝脏中HO-1表达增加,其中45μg·kg-1剂量组增加效果最为明显,约为4.5倍;NF-κB的核内水平随给药剂量增加而降低,180μg·kg-1剂量组NF-κB的降低至空白对照组的约1/3;NF-κB的核内水平随给药剂量增加而降低。结论重复给予雷公藤甲素可诱导大鼠肝脏中HO-1表达,抑制NF-κB的转位入核,从而对抗氧化应激和炎症反应。     

酒石酸布托啡诺基于JNK/NF-κB信号通路对大鼠脑缺血再灌注损伤的改善作用

目的 探讨酒石酸布托啡诺对大鼠脑缺血再灌注损伤(CIRI)的改善作用,并分析相关作用机制。方法 80只大鼠随机分为假手术组、模型组、酒石酸布托啡诺组、尼莫地平组,每组20只。采用Zea Longa法评估大鼠神经功能,检测大鼠脑含水量,TTC染色法检测大鼠脑梗死体积比,HE染色观察大鼠脑组织病理性改变,TUNEL法检测大鼠脑组织细胞凋亡,Western blot法检测炎性因子和通路相关蛋白表达。结果 与假手术组比较,模型组大鼠存在明显脑组织病理损伤,大鼠神经功能评分、脑含水量、脑梗死体积比均增高,脑组织细胞凋亡水平和炎性因子肿瘤坏死因子α(TNF-α)、白介素-1β(IL-1β)、白介素-6(IL-6)表达升高,磷酸化c-Jun氨基末端激酶(p-JNK)、核因子-κB(NF-κB)、核因子κB磷酸化65(p65)蛋白表达上调,差异均有统计学意义(P<0.05)。与模型组比较,酒石酸布托啡诺和尼莫地平能够有效改善CIRI大鼠脑组织病理损伤,降低神经功能评分,减少大鼠脑含水量和脑梗死体积比,并降低脑组织细胞凋亡水平和炎性因子表达,下调p-JNK、NF-κB、p65蛋白表达,差异均有统计...     

葡萄籽原花青素对大鼠脑缺血再灌注后NF-κB、IκB和iNOS的影响

目的 探讨葡萄籽原花青素(GSPE)对大鼠脑缺血再灌注后NF-κB,IκB和iNOS的影响.方法 采用线栓法建立大鼠右侧大脑中动脉缺血再灌注模型.将72只SD大鼠随机均分成假手术组、缺血再灌注组和GSPE组,于缺血2 h再灌注6、24、48 h时断头取脑,选取视交叉前后各1 mm的脑组织,采用免疫组化法检测核因子-κB(NF-κB)、抑制蛋白-κB(IκB)、诱导型一氧化氮合酶(iNOS)的表达,观察GSPE对其的影响.结果 缺血再灌注组NF-κB的表达较GSPE组显著增加(P＜0.01),而IκB表达却显著减少.结论 局灶性脑缺血再灌注时,GSPE可通过抑制IκB的降解及NF-κB的活性、下调iNOS的表达,而起脑保护作用.     

西红花酸对大鼠脑缺血再灌注Caspase-3mRNA和NF-κB表达的影响

目的:探讨西红花酸对脑缺血再灌注Caspase-3mRNA和NF-κB表达的影响。方法:SD大鼠随机分为6组,即假手术组、模型组、尼莫地平组(5 mg.kg-1)和西红花酸组(10,20,40 mg.kg-1)。假手术组、模型组给予等容量的生理盐水。各组大鼠每日上午灌胃给药1次,连续给药7 d。采用线栓法阻塞大脑中动脉制备局灶性脑缺血2 h再灌注22 h模型。观察大鼠神经功能缺陷评分、脑梗死体积,测定脑组织GSH-Px活性及Caspase-3mRNA和NF-κB表达。结果:西红花酸呈剂量依赖性的降低脑组织梗死体积、改善神经功能,增加脑组织GSH-Px活性,减少Caspase-3mRNA和NF-κB表达。结论:西红花酸可能通过增加GSH-Px活性,减少Caspase-3mRNA和NF-κB表达,保护脑缺血再灌注损伤。     

NF—κB、TNF—α在淹溺大鼠脑组织中的表达及其与脑损伤的相关性

目的:探讨淡水淹溺后大鼠脑组织中细胞因子NF-κB、TNF-α的表达及其与淹溺应激引起脑损伤之间的关系。方法:Wistar大鼠70只,其中正常对照(Ⅰ组)、溺水致死(Ⅱ组)、溺水后存活(Ⅲ组)3h、6h、12h、24h、40h各10只,剥取脑组织固定、切片,HE染色后光镜下观察形态学改变;SABC免疫组化法检测各组大鼠脑组织中NF-κB、TNF-α的表达。结果:Ⅰ组脑组织结构清晰,无水肿、出血、坏死病灶;Ⅱ组脑实质疏松,小血管周隙增宽,部分神经细胞体积增大变性;Ⅲ组随溺水后存活时间的推移,脑损伤程度逐渐加重,其中24h脑水肿最重,40h个别脑实质小灶性液化性坏死。Ⅱ组脑指数明显高于Ⅰ组(P<0.05),并高于Ⅲ组,与3h、6h、12h差异有统计学意义(P<0.05)。与Ⅰ组相比,Ⅲ组6h时NF-κB表达显著增加(P<0.05);12h时TNF-α表达显著增加(P<0.05)。结论:淡水淹溺后存活大鼠发生脑损伤时NF-κB和TNF-α高表达,提示NF-κB、TNF-α与淹溺应激所致脑损伤有关。     

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.     

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.     

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.