双环醇对大鼠肝脏缺血再灌注损伤的保护作用

目的：研究双环醇对大鼠肝脏缺血再灌注损伤的作用及相关作用机制。方法：采用Yoshizumi法制备肝脏缺血再灌注损伤模型，缺血90min后再灌注lh、3h、6h和24h，观察双环醇对血清丙氨酸氨基转移酶（ALT）、乳酸脱氢酶（IDH）和总胆红素（TBil）及肝组织丙二醛（MDA），超氧化物岐化酶（S（）D）、髓过氧化物酶（MPO）、一氧化氮（NO）和诱导型一氧化氮合酶（iNOS）的影响。同时测定再灌后不同时间点血中内毒素水平；应用RT-PCR方法检测TNF-α、IL-1β、IL-6和IL-10表达；应用免疫组化方法检测再灌3h时肝脏ICAM-1和P-selectin含量以及肝脏组织病理学改变。结果：双环醇（300mg／kg）可显著抑制大鼠肝脏缺血再灌注损伤后血清ALT、LDH和TBil水平升高，降低升高的肝组织MDA、MPO、N0和iNOS含量，抑制肝组织SOD水平降低，明显减轻肝脏水样空泡样变性、炎症浸润和坏死，抑制血中内毒素水平升高。双环醇还可显著抑制炎症因子TNF-α、IL-1β、IL-6的高表达，促进抗炎因子IL-10表达，显著抑制肝组织粘附分子ICAM-1和P-selectin含量的升高。结论：双环醇对大鼠肝脏缺血再灌注损伤具有明显的保护作用，其保护作用与抑制肝脏脂质过氧化、改善肠内毒素的转位以及调控炎症因子／抗炎因子表达密切相关。     

豹皮樟总黄酮对酒精性脂肪肝大鼠脂质过氧化及TNF-α生成的影响

目的：研究豹皮樟总黄酮（TFLC）对酒精性脂肪肝大鼠的保护作用及其部分机制方法：喂食酒精、蔗糖混合液体食料制备大鼠酒精性脂肪肝模型。给药组在第6周末给予不同剂量的豹皮樟总黄酮或凯西莱共给药6周。于实验的第12周末处死大鼠,测定血清天门冬氨基转移酶（AST）、丙氨酸氨基转移酶（ALT）、肿瘤坏死因子-α（TNF—α）的水平,肝组织超氧化物岐化酶（SOD）、丙二醛（MDA）、谷胱甘肽过氧化物酶（GSH-PX）的含量及肝组织TNF-αmRNA的表达情况,取肝组织作病理学检查。结果：TFLC能降低模型大鼠ALT、AST、MDA、TNF-α的含量,提高SOD、GSH-PX的含量,肝组织TNF-αmRNA表达下降。同时病理学显示TFLC能明显减轻肝的病理损伤程度,表现为TFLC干预后大鼠肝细胞脂肪变及炎症程度减轻。结论：TFLC能可明显减轻酒精性脂肪肝大鼠肝组织脂肪变和炎症程度,减轻脂质过氧化,并能显著降低血清TNF—α水平,减少肝组织TNF—αmRNA表达,该作用可能是其有效防治酒精性脂肪肝作用机理机制之一。     

青蒿琥酯对盲肠结扎穿孔术脓毒症小鼠的保护作用

目的:探讨青蒿琥酯(AS)对盲肠结扎穿孔术(CLP)脓毒症小鼠的保护作用及其可能机制。方法:采用CLP制作小鼠脓毒症模型,术后0、4、24、48h重复肌肉注射AS,观察7d内CLP小鼠的死亡率;检测术后4、8h血浆脂多糖(LPS)、TNF-α、IL-6水平;术后8h小鼠肺脏组织形态的变化。结果:AS明显降低CLP小鼠的死亡率(P<0.05)及血浆LPS、TNF-α和IL-6水平(P<0.05或P<0.01),减轻肺组织的损伤。结论:AS对CLP小鼠具有显著的保护作用,该作用可能与其降低血浆LPS水平、减少促炎细胞因子TNF-α、IL-6的释放和减轻组织脏器的损伤有关。     

连翘苷元对四氯化碳大鼠急性肝损伤的保护作用

目的探讨连翘苷元对四氯化碳(CCl4)所致急性肝损伤的保护作用。方法用CCl4诱导化学性急性肝损伤模型,测定血清中丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、总胆红素(TBIL)水平;肝脏组织切片,苏木精-伊红(HE)染色,光镜观察病理学改变;用试剂盒测定肝组织中SOD、GSH-Px和GSH的活性及脂质过氧化产物MDA含量。ELISA法检测血清中TNF-α、IL-8含量。结果在CCl4诱导的大鼠急性肝损伤模型中,连翘苷元(0.05、0.15、0.5mg·kg-1,sc)明显降低血清ALT、AST和TBIL水平;明显改善肝脏病理组织状况;连翘苷元(0.05、0.15、0.5 mg·kg-1,sc)明显降低CCl4诱导的急性肝损伤大鼠的肝组织匀浆中MDA的含量,明显增加SOD、GSH-Px和GSH的活性。连翘苷元(0.15、0.5 mg·kg-1,sc)明显降低TNF-α、IL-8含量。结论连翘苷元对CCl4诱导大鼠急性肝损伤具有保护作用,该作用与其增加肝组织中抗氧化酶的活性、降低脂质过氧化水平、降低TNF-α、IL-8等促炎因子水平有关。     

七味净肝灵对卡介苗联合脂多糖诱导的小鼠免疫性肝损伤的保护作用及其机制

目的：研究七味净肝灵（牛大力、黑老虎、地耳草、叶下珠、虫牙药、白花蛇舌草、甘草）对卡介苗（BCG）+脂多糖（LPS）诱导的免疫性肝损伤小鼠的保护作用及其作用机制。方法：建立BCG+ LPS致小鼠免疫性肝损伤模型,取血,收集肝脏,脾脏和胰腺。生化法测定血清中ALT, AST, MDA, SOD的活性或含量,ELISA法检测肝组织中IL-4,IL-6和NO含量,Western-blot分析肝组织中TNF-α和NF-κB蛋白的表达情况;HE染色,显微镜观察肝组织病理改变。结果：七味净肝灵各剂量组可降低免疫性肝损伤小鼠血清或肝组织中ALT、AST、MDA、IL-4,IL-6和NO的活性或含量,抑制肝组织中TNF-α和NF-κB蛋白的表达,升高SOD活性;病例检查显示其各剂量组均能显著改善肝组织坏死损伤。结论：七味净肝灵对BCG+ LPS诱导的小鼠免疫性肝损伤有明显的保护作用,其机制可能通过抗脂质过氧化、抑制肝内的炎症反应及细胞毒性作用来介导保肝作用。     

乌司他丁对糖尿病脓毒症大鼠急性肾损伤的保护作用

目的 探讨乌司他丁(UTI)对糖尿病脓毒症大鼠肾损害的作用及其机制.方法 采用高脂饲料喂养+腹腔小剂量注射链脲佐菌素方法制备大鼠2型糖尿病模型,取造模成功的大鼠40只随机分为4组,每组10只:糖尿病组(D组)、糖尿病假手术组(S组)、糖尿病脓毒症组(DS组)、糖尿病脓毒症UTI预处理组(U组).另随机抽取同批次大鼠10只,作C组空白对照.采用盲肠结扎穿孔术(CLP)构建脓毒症模型.U组于CLP前1 h予尾静脉注射UTI 100 kU·kg-1.S组拉出盲肠至腹外放置1 min.于CLP术后12 h,检测各组大鼠肾组织病理情况,定量尿微量白蛋白(UMA),内生肌酐清除率(Ccr),血清肿瘤坏死因子-α(TNF-α)、白细胞介素-18(IL-18)含量,血清丙二醛(MDA)、超氧化物歧化酶(SOD)水平,以及肾组织低氧诱导因子-1α(HIF-1α)的蛋白表达水平.结果 与S组相比,DS组大鼠肾脏病理损害明显,UMA、IL-18、TNF-α、MDA、HIF-1α水平增高,Ccr和SOD活性降低(均P<0.05).DS组相比,U组大鼠肾脏病理损害减轻,UMA、IL-18、TNF-α、MDA含量、HIF-1α水平降低,Ccr和SOD活性增高(均P<0.05).结论 UTI可有效改善糖尿病脓毒症所致急性肾损伤大鼠的肾脏功能,其机制可能与抑制炎性反应、降低氧化应激、改善肾脏缺氧情况有关.     

青蒿素对大鼠肝脏微粒体过氧化损伤的影响

观察青蒿素体外对细胞微粒体过氧化损伤的影响。方法：采用提取大鼠肝脏微粒体方法,建立体外ＮＡＤＰＨ／ＶｉｔＣ诱发大鼠肝脏微粒体脂质过氧化损伤模型,观察青蒿素对减少肝脏微粒体脂质过氧化物的形成作用。结果;青蒿素能明显减少肝微粒体脂质过氧化物的形成（Ｐ＜０．０５～０．０１）。结论：青蒿素能抵抗细胞微粒体的过氧化损伤,此为其治疗机理之一。     

槲皮素对INH诱导的大鼠肝脏氧化损伤的影响

目的：观察槲皮素对异烟肼（INH）致大鼠肝脏氧化损伤的保护作用。方法：将动物随机分为正常对照组、INH损伤组、槲皮素低剂量组、槲皮素高剂量组,灌胃染毒,每天1次,14d后测定大鼠血和肝匀浆中丙二醛（MDA）含量,谷胱甘肽过氧化物酶（GSH-Px）和超氧化物歧化酶（SOD）活性。结果：与INH组比较,槲皮素高剂量组大鼠血清和肝组织的MDA含量降低（P〈0.01或P〈0.05）,而SOD和GSH-Px活性增加（P〈0.05）。结论：槲皮素对INH所致的大鼠肝脏损伤具有保护作用,可能与其抗脂质过氧化作用有关。     

Effect of melatonin on the inflammatory factors in serum of rats with endotoxemia

目的 探讨褪黑素(MT)对脂多糖(LPS)诱导的内毒素血症大鼠炎性因子肿瘤坏死因子-α(TNF-α)、白介素-6(IL-6)和抗炎因子IL-10表达的影响.方法 雄性SD大鼠48只,分为溶剂对照组、LPS 组、LPS+ MT组、MT组,每组12只.检测各组大鼠血清超氧化物歧化酶(SOD)和丙二醛(MDA)的含量;应用酶联免疫吸附法(ELISA)检测血清TNF-α、IL-6和IL-10含量.结果 LPS+MT组的血清SOD活性较LPS组明显增高(P＜0.01),MDA含量较LPS组明显降低(P＜0.01);LPS组大鼠血清TNF-α,IL-6含量明显上升,与对照组比较差异有统计学意义(P＜0.01),而给予LPS前后应用MT干预治疗,可显著降低血清TNF-α、IL-6含量,与同时间点LPS组比较均差异有统计学意义(P＜0.01).结论 MT可以降低内毒素血症大鼠血清炎性因子水平.     

复方软肝颗粒抗肝纤维化作用的实验研究

目的 探讨复方软肝颗粒对大鼠化学性肝纤维化的抑制作用及其可能机制。方法 用CCl4皮下注射诱导化学性肝纤维化大鼠模型,再以不同剂量的复方软肝颗粒进行干预,并测定血清中ALT、AST、HA、LN、PCⅢ、TNF-α、IL-1β以及肝组织中SOD、MDA的含量。结果 复方软肝颗粒可降低血清中ALT、AST及HA、LN、PCⅢ、TNF-α、IL-1β含量;同时降低肝组织中MDA含量,提高血清SOD活性。结论 复方软肝颗粒具有明显的降酶、保护肝细胞和抗肝纤维化作用,其机制可能与阻断氧化应激过程,抑制脂质过氧化,减少炎症细胞因子的释放等有关。     

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.     

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.