健脑益智汤对阿尔茨海默病大鼠海马凋亡蛋白表达的影响

目的研究健脑益智汤对阿尔茨海默病(AD)大鼠海马凋亡相关蛋白表达的影响,探讨其治疗AD的可能机制。方法正常老年大鼠50只,分为对照组、AD模型组、多奈哌齐组和健脑益智汤大剂量和小剂量组。除对照组外,其余各组采用左侧侧脑室注射Aβ25-35建立AD大鼠模型,并按药物规定剂量灌胃1个月。取海马,蛋白印迹法测凋亡相关蛋白的表达水平。结果与对照组比,AD模型组凋亡相关蛋白细胞色素C(Cyt-C)、胱天蛋白酶(caspase)-3和caspase-9表达增加(P<0.05或P<0.01);除健脑益智汤小剂量组外,其余用药组CytC、caspase-3和caspase-9蛋白水平较AD模型组有明显降低(P<0.05或P<0.01);而健脑益智汤大剂量组与多奈哌齐组相比较,caspase-3蛋白表达水平降低较为明显(P<0.05)。结论健脑益智汤能降低AD大鼠海马Cyt-C、caspase-3和caspase-9蛋白的表达水平。     

老年大鼠脑室注射β-淀粉样肽制作阿尔茨海默病模型的实验研究

目的探讨一种新的阿尔茨海默病(AD)大鼠模型与人类AD的相似程度。方法选用正常老年Wistar大鼠,左侧侧脑室注射5μL聚集态的Aβ25-35,通过血清乙酰胆碱酯酶(AChE)的检测和流式细胞仪细胞凋亡测定,比较AD模型大鼠和正常老年大鼠的差异。结果模型组血清AChE活力和脑皮质细胞凋亡百分率均较正常大鼠增大(P<0.05或P<0.01)。结论老年大鼠侧脑室注射聚集态的Aβ25-35的方法可作为制作AD动物模型的方法之一。     

醒脑益智组分中药对AD大鼠学习记忆及氧化应激-凋亡相关研究

目的： 观察醒脑益智组分中药对阿尔茨海默病（AD）模型大鼠学习记忆功能的影响及对氧化应激-凋亡相关机制的调控。方法： 采用D-半乳糖（D-gal）腹腔注射联合β-淀粉样蛋白1-40（Aβ_1-40）海马内注射的复合造模方法建立AD动物模型,实验分为假手术组、AD模型组、石杉碱甲0.05 mg·kg^-1组、醒脑益智组分中药179.2、89.6、44.8 mg·kg^-1组。以Morris水迷宫检测大鼠学习记忆能力,苏木-伊红（HE）染色观察大鼠脑组织病理学形态变化,酶联免疫吸附试验（ELisa法）检测脑组织及血清超氧化物歧化酶（SOD）活力、脂质过氧化物丙二醛（MDA）含量,免疫组化检测凋亡相关蛋白Bcl-2、Caspase-3的表达。结果： 与模型组比较,各给药组大鼠逃避潜伏期降低,穿台次数增加,穿越第四象限的路程百分比也均有提高,以阳性药物和高、中剂量组作用有显著性差异（P<0.05）;各给药组能明显改善AD大鼠脑部神经元细胞形态;药物高、中剂量组能使AD大鼠脑组织及血清中SOD活性提高,MDA含量明显降低（P<0.05）,Bcl-2表达量升高,Caspase-3表达量减少。结论： 醒脑益智组分中药对复合造模致AD模型大鼠学习记忆障碍具有一定改善作用,这可能与抗氧化及抗凋亡的脑保护作用有关。     

醒神液抑制阿尔茨海默病模型大鼠脑神经细胞凋亡的观察

目的从抑制脑神经细胞凋亡观察醒神液对阿尔茨海默病(Alzheimer disease,AD)的治疗作用及机理。方法用D-半乳糖和鹅膏蕈氨酸制备大鼠AD模型,并同时用醒神液对其进行治疗,采用TUNEL和图像分析法观察脑皮质和海马神经细胞凋亡的变化。结果醒神液治疗组脑皮质及海马神经元凋亡数及凋亡积分光密度明显降低,治疗效果高剂量组优于低剂量组,呈明显量效关系。结论醒神液能减轻AD模型大鼠神经细胞凋亡,对AD有一定的防治作用。     

吡拉西坦联合盐酸多奈哌齐对阿尔茨海默病大鼠海马区小胶质细胞活化的影响

目的 探讨吡拉西坦(PT)联合盐酸多奈哌齐(DH)对阿尔茨海默病(AD)大鼠海马区小胶质细胞活化的影响.方法 双侧海马注射凝聚状态Aβ1-42法建立AD模型.50只大鼠按照体质量随机分为假手术组、模型组、对照A组、对照B组和实验组,每组10只.除假手术组外,其余4组建立AD大鼠模型.模型制备成功后,开始给药.对照A组灌...     

抵当汤对阿尔茨海默病大鼠脑组织端粒酶活性的影响

目的观察抵当汤对阿尔茨海默病(AD)大鼠脑组织端粒酶活性及学习记忆能力的影响。方法 40只雄性Wistar大鼠随机分为假手术组、模型组、多奈哌齐组和抵当汤组。采用右侧海马注射Aβ25-35方法制备AD大鼠模型,治疗组采用抵当汤治疗,对照组给予多奈哌齐,均连续灌胃给药,疗程为8周,采用跳台实验观察各组大鼠学习记忆能力的改变。实验结束后处死大鼠,采用ELISA检测脑组织端粒酶活性。结果实验结束后各用药组逃避潜伏期较模型组明显延长,错误次数明显减少(P<0.05,P<0.01),抵当汤组较多奈哌齐组错误次数减少更明显(P<0.05);与模型组比较,抵当汤组和多奈哌齐组脑组织端粒酶活性明显提高(P<0.05,P<0.01),抵当汤组较多奈哌齐组提高更明显(P<0.05)。结论抵当汤可显著改善AD大鼠的学习记忆能力,其机制可能与该方提高大鼠脑组织端粒酶活性有关。     

α-硫辛酸对糖尿病大鼠肾脏氧化应激及细胞凋亡的影响

目的 探讨氧化应激在糖尿病大鼠肾脏细胞凋亡中的作用以及α-硫辛酸的肾保护作用.方法 腹腔注射链脲佐菌素诱导糖尿病模型,并将糖尿病大鼠分为糖尿病非干预组(DM组)、α-硫辛酸干预组(LA组),非糖尿病正常大鼠作对照(NC组),每组10只.12周时检测肾皮质中丙二醛(MDA)含量及超氧化物歧化酶(SOD)的活性;原位末端标记(TUNEL)法检测肾脏细胞凋亡,免疫组化法检测半胱氨酸蛋白酶3(Caspase-3)的表达.结果 与NC组相比,DM组肾皮质MDA含量显著升高(P<0.01),SOD活性显著下降(P<0.01);肾脏凋亡细胞数及Caspase-3表达均显著增加(P<0.01).α-硫辛酸干预后可改善上述指标(P<0.01).结论 糖尿病可引起肾脏高水平的氧化应激和过度的细胞凋亡.α-硫辛酸通过抑制氧化应激和下调Caspase-3的表达来干预细胞凋亡发挥肾保护作用.     

益智康脑丸对老年性痴呆大鼠行为学及脑组织Bcl-2和Bax蛋白表达的影响

目的:探讨益智康脑丸对老年性痴呆(AD)大鼠行为学及脑组织凋亡蛋白的影响。方法:复制D-半乳糖AD大鼠模型。实验分为4组,即空白、模型、益智康脑丸和脑复康组,检测大鼠行为学及脑组织抑制细胞凋亡基因Bcl-2和促凋亡基因Bax表达指标的改变。结果:模型组与空白组比较,学习记忆能力显著下降,Bcl-2/Bax比值下降;治疗组与模型组比较,学习记忆能力显著改善,Bcl-2/Bax比值增加。结论:益智康脑丸具有较好的治疗AD作用,其机制可能与促进AD大鼠脑组织Bcl-2的表达、降低Bax的表达有关。     

银杏叶提取物对Aβ25-35诱导的神经细胞毒性的防治作用

目的探讨银杏叶提取物对Aβ25-35诱导体外培养神经细胞毒性的防治作用。方法 培养大鼠大脑皮质神经元细胞,构建AD细胞模型,制模前后加用银杏叶提取物(EGb)干预,四甲基噻唑蓝比色法(MTT)测定神经细胞活力,West-ern印迹分析法测Caspase3、Bcl-2、Bax表达。结果 EGb显著提高预防组细胞活力(P<0.01),增强预防组及治疗组Bcl-2表达(P<0.01),明显抑制预防组及治疗组Caspase3、Bax表达(P<0.01)。结论 EGb可有效的对抗Aβ25-35的神经毒性作用,抑制细胞凋亡。     

灯盏花素对大鼠脑缺血再灌注损伤后SOD和细胞凋亡的影响

目的:研究灯盏花素对大鼠脑缺血再灌注(I-R)损伤后超氧化物歧化酶(SOD)和细胞凋亡的影响。方法:实验分为5组,即假手术、I-R、MgSO4及灯盏花素高、低剂量组。采用线栓法制备大鼠脑I-R损伤模型,观察大鼠脑组织和血清SOD活性,以及脑细胞凋亡情况。结果:与假手术组比较,I-R组大鼠脑组织和血清中SOD活性显著降低(P<0.01),脑细胞凋亡率显著升高(P<0.01);与I-R组比较,灯盏花素高、低剂量组大鼠脑组织和血清中SOD活性显著增强(P<0.01),脑细胞凋亡率显著降低(P<0.01)。结论:灯盏花素对脑I-R损伤模型大鼠有保护作用,其机制可能与增强SOD活性和减少细胞凋亡等作用有关。     

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.     

Synthesis,Cytotoxicity and Antileishmanial Activity of Some N-(2-(indol-3-yl)ethyl)-7-chloroquinolin-4-amines

We report herein the condensation of 4,7-dichloroquinoline (1) with tryptamine (2) and D-tryptophan methyl ester (3) . Hydrolysis of the methyl ester adduct (5) yielded the free acid (6) . The compounds were evaluated in vitro for activity against four different species of Leishmania promastigote forms and for cytotoxic activity against Kb and Vero cells. Compound (5) showed good activity against the Leishmania species tested, while all three compounds displayed moderate activity in both Kb and Vero cells.     

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.     

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.