基于Ca2+-CaMKⅡ信号通路的济川煎治疗阳虚便秘的作用及分子机制

目的 基于Ca²⁺-CaMKⅡ通路观察济川煎对阳虚便秘大鼠的治疗作用及分子机制。方法 采用白醋+活性炭冰水联合复方地芬诺酯片复制阳虚便秘大鼠模型。将模型成功大鼠随机分为5组,即模型组、莫沙必利组(1.88 mg·kg^-1)、济川煎高(8.26 g·kg^-1)、中(4.31 g·kg^-1)、低(2.16 g·kg^-1)剂量组,灌胃给药每日1次,连续7 d。末次给药,记录大鼠状态并评分,进行排便功能测定;分离模型大鼠结肠平滑肌细胞并鉴定,FCM检测结肠平滑肌细胞内Ca²⁺浓度变化;采用ELISA法检测大鼠血清中cAMP、cGMP含量及其比值;采用RT-PCR及Western blot法检测大鼠结肠平滑肌细胞CaM、CaMKⅡ亚型的表达情况。结果 济川煎可明显缓解模型大鼠腹胀,摄食、饮水量、排便减少及体质量降低的症状(P<0.05),评分明显升高(P<0.01);能明显缩短首粒排便时间(P<0.01),增加排便粒数(P<0.05);济川煎...     

合生元对小鼠便秘及肠推进作用的研究

目的研究合生元对小鼠便秘及肠推进作用的影响。方法将昆明雄性小鼠随机分为正常对照组、模型对照组和4个剂量的给药组,给药组分别经口给予不同浓度的合生元(1、3、5、10 g.kg-1)0.2 mL.(10 g·d)-1空白组和模型组给予0.2 mL.(10 g·d)-1的生理盐水。用复方地芬诺酯制造小鼠便秘模型,建模后各组分别给药,观察各组小鼠的首次排黑便时间、5 h内排便粒数、粪便质量和小肠墨汁推进率。结果合生元给药15 d,可明显改善便秘小鼠首次排黑便时间、增加排黑便粒数和质量;同时可显著提高便秘小鼠小肠墨汁推进率。结论表明该合生元具有润肠通便功能。     

苦丁茶提取物对小鼠通便作用研究

目的:研究苦丁茶提取物对便秘模型小鼠通便作用的影响.方法:采用复方地芬诺酯(DC)10 mg·kg-1制备小鼠便秘模型,分别灌胃给予0.4,0.8,1.2g· kg-1 ·d-1三个剂量苦丁茶提取物7d,qd,观察苦丁茶提取物对小鼠体质量、小肠推进运动和给药后6h内排便的影响.结果:苦丁茶提取物高、中剂量组能促进DC便秘模型小鼠的小肠推进率、缩短首次排便时间、增加6h内的排便总数;低剂量苦丁茶组与模型组相比,能缩短首次排便时间(P＜0.05),但两组对小肠推进率和排便总数差异无统计学意义(P＞0.05);中、高剂量组小鼠6h内粪便质量与模型对照组比较,差异有统计学意义(P＜0.05或0.01).结论:苦丁茶提取物能促进复方地芬诺酯致小鼠便秘模型的排便作用.     

唐古特大黄根茎不同组织的红外光谱分析及药效学的对比研究

目的 利用红外光谱分析唐古特大黄根茎不同组织中成分分布特征,同时对比研究唐古特大黄根茎不同组织的泻下及抗炎作用。方法 使用溴化钾压片法对样品进行红外光谱测定。（1）将小鼠随机分为空白组、模型组、唐古特大黄根茎组、传统药材组和外皮层组。空白组灌胃蒸馏水(20 mL·kg^-1),其余各组灌胃复方地芬诺酯(50 g·kg^-1)复制便秘模型。空白组与模型组灌胃空白对照液(20 mL·kg^-1),其余给药组分别灌胃加入碳素墨汁的唐古特大黄根茎药液、传统药材药液、外皮层药液(均为4 g·kg^-1)。给药后观察小鼠首次排黑便时间、5 h内排便次数及测定肠道含水量,次日,灌胃1 h后,用酶联免疫吸附法（ELSA）测定小鼠结肠Na⁺-K⁺-ATP酶活性。（2）用二甲苯致小鼠耳肿胀法、甲醛致小鼠足肿胀法建立炎症模型,将小鼠随机分为即模型组、唐古特大黄根茎组、传统药材组和外皮层组。模型组灌胃蒸馏水(20 mL·kg^-1),其余给药组分别灌胃唐古特大黄根茎药...     

夏黄颗粒治疗慢传输型便秘的实验研究

目的 采用吗啡致小鼠慢传输型便秘模型,评价夏黄颗粒的治疗作用,并对其通便作用进行实验研究。方法 采用连续sc 2.5 mg/kg盐酸吗啡45 d致小鼠慢传输型便秘模型,观察夏黄颗粒的通便作用;采用1次性ip 5 mg/kg盐酸吗啡致小鼠小肠推进、胃排空抑制模型,观察夏黄颗粒对胃肠抑制的拮抗作用;采用测定小鼠小肠湿、干质量法,观察夏黄颗粒对肠水分吸收的作用;采用顺铂致大鼠异嗜模型,观察夏黄颗粒的止吐作用;采用吗啡致豚鼠离体回肠、结肠痉挛模型,观察夏黄颗粒的作用及机制。结果 与模型组比较,小鼠给药5 d,夏黄颗粒14.95、7.48 g生药/kg能显著增加慢传输型便秘小鼠的24 h排便量（P<0.05、0.01）,继续给药至7 d,14.95、7.48 g生药/kg能显著增加小肠推进率、14.95 g生药/kg显著升高血清P物质含量（P<0.05、0.01）;给药1次,14.95、7.48 g生药/kg剂量组能显著增加小鼠小肠推进率、加快胃排空（P<0.01）,14.95 g生药/kg显著增加小鼠小肠含水量（P<0.01）;大鼠给药3 d,10.35 g生药/kg剂量组能显著降低大鼠异嗜高岭土质量（P<0.05）;给药1次,2.49、1.25 mg生药/mL（浴槽终浓度）能显著降低吗啡所致痉挛性回肠的肠张力（P<0.01）,2.49、1.25、0.62 mg生药/mL（浴槽终浓度）能显著降低吗啡所致痉挛性结肠的肠张力（P<0.05、0.01）。结论 夏黄颗粒对吗啡所致慢传输型便秘有显著的治疗作用,具有显著的通便、解痉、促进胃肠运动、肠吸收及止吐作用。     

魔芋醇提取物急性毒性试验及初步药效作用研究

目的：考察魔芋醇提取物的急性毒性和药理作用研究。方法：采用单次灌胃给药考察魔芋醇提取物的急性毒性,采用小鼠肠推进实验考察魔芋醇提取物的促消化和润肠通便作用;采用S180和H22小鼠抑瘤实验考察魔芋醇提取物的抗肿瘤活性。结果：急性毒性试验,魔芋醇提物24 h内小鼠灌胃给药LD₅₀为19.18 g﹒kg^-1(相当于生药165.34 g﹒kg^-1);小鼠肠推进实验,与空白对照组比较,魔芋醇提取物低剂量组和高剂量组小鼠小肠的墨汁推进百分率均显著升高(均P<0.01),抗肿瘤作用研究,与空白对照组比较,魔芋醇提取物低剂量组和高剂量组可以显著降低小鼠瘤重(P<0.05或P<0.01);魔芋醇提取物高剂量组对H22移植瘤小鼠的胸腺指数和脾脏指数均显著增加(P<0.05或P<0.01)。结论：魔芋醇提取物具有显著的促消化,润肠通便的功效;可以抑制S180和H22肿瘤细胞的生长,具有显著的抗肿瘤活性;且具有一定的毒性。     

川、浙厚朴缓解小鼠便秘作用的药效比较

目的在已经测定了四川和浙产厚朴中厚朴酚类含量的基础上,进一步比较四川厚朴与浙产厚朴缓解便秘作用的药效,为厚朴临床应用提供参考。方法通过小鼠小肠墨汁推进实验,观察川、浙厚朴对小鼠小肠运动的影响;应用燥结致便秘模型,观察两种厚朴对小鼠首次排黑便时间、6 h排便粒数及排便量的影响;应用复方地芬诺酯致便秘模型,观察两种厚朴对小鼠首次排黑便时间、6 h排便粒数及排便量的影响。结果四川厚朴(15 g·kg-1)能明显提高小鼠墨汁的推进率(P0.05);四川厚朴(5 g·kg-1)和浙产厚朴(15 g·kg-1)均能缩短燥结便秘模型小鼠首次排黑便时间。四川厚朴(15 g·kg-1)增加6 h排便粒数和排便量;四川厚朴(15 g.kg-1)能缩短复方地芬诺酯致便秘小鼠首次排黑便时间,增加6 h排便粒数和排便量。四川厚朴(10 g·kg-1)和浙产厚朴(15 g·kg-1)均增加6 h排便粒数。浙产厚朴(10 g·kg-1)缩短便秘模型小鼠首次排黑便时间。浙产厚朴(5 g·kg-1)增加6 h排便量。结论四川厚朴能促进小鼠小肠推进运动,两种厚朴能缓解复方地芬诺酯致便秘小鼠的便秘。浙产厚朴与四川厚朴在该方面药效未见明显差异。     

小鼠低纤维膳食便秘模型的初步研究

目的通过给予小鼠特制低纤维饲料,建立小鼠低纤维膳食便秘模型,并采用富含膳食纤维的样品进行模型验证。方法设5个组:普通饲料阴性对照组、低纤维饲料模型组(Low-fiber-diet,LFD)和高纤样品3个剂量组(146. 75,1 467. 5和4 402. 5 mg/kg·bw)。每组20只小鼠,10只用于小肠运动试验,另10只用于排便试验。普通饲料阴性对照组5周内持续给予普通饲料,第22天开始给予蒸馏水; LFD组5周内持续给予低纤维饲料,第22天开始给予蒸馏水;高纤样品3个剂量组5周内持续给予低纤维饲料,第22天开始给予小鼠相应剂量样品。所有动物经口灌胃1次/d,共14 d;试验第36天进行小肠运动试验和小鼠排便试验。结果小肠运动试验结果显示:LFD组与阴性对照组小鼠比较、高纤样品各剂量组与LFD组比较,小鼠小肠推进率差异均无统计学意义(P0. 05)。小鼠排便试验结果显示:LFD组与阴性对照组比较,6 h排便粒数减少、粪便湿重降低、粪便干重降低且排便时间延长,差异均有统计学意义(P0. 01),提示模型成立。高纤样品低剂量组与LFD组比较,排便时间缩短(P0. 01);其他参数比较差异无统计学意义(P0. 05)。高纤样品中、高剂量组与LFD组比较,6 h便粒数增加、粪便湿重增加、粪便干重增加且排便时间缩短,差异均有统计学意义(P0. 01)。结论小鼠排便试验低纤维膳食便秘模型成立,给予高纤样品后可改善小鼠便秘情况,具有润肠通便的功能。在小肠运动试验中,低纤维膳食便秘模型不成立可能与其便秘机制与试验原理不一致有关,尚需进一步研究。     

川芎嗪对异丙肾上腺素诱导的小鼠急性心肌缺血的保护作用

目的研究川芎嗪（TMP）对异丙肾上腺素（ISO）诱导的小鼠急性心肌缺血的保护作用及其机制。方法小鼠按照体重随机分为正常组(生理盐水10mg·kg^-1·d^-1)、模型组(ISO 3 mg·kg^-1·d^-1,连续3 d每天1次)、对照组(普萘洛尔0.4 mg·kg^-1·d^-1)、3个剂量TMP组(TMP 60,30,15 mg·kg^-1·d^-1),连续给药7 d。记录小鼠心电图,全自动生化分析仪测定血清肌酸激酶同工酶（CK-MB）、乳酸脱氢酶（LDH）、过氧化氢（H₂O₂）和总抗氧化能力（T-AOC）的变化;HE和TTC染色观察心肌病理损伤和梗死情况。结果 TMP能明显改善ISO诱导的心电图ST段偏移以及心肌损伤,缩小梗死面积。与模型组[CK-MB:（1562.46±138.92）U·L^-1;LDH:（6973.28±285.50）U·L^-1;T-AOC:（2.99±1.25）U·mL^-1;H₂O₂:（92.52±11.42）mmol·L^-1]比较,TMP各组的[CK-MB:（605.81±117.72）,（838.67±159.73）,（1264.37±134.17）U·L^-1);LDH:（2661.79±229.27）,（5776.16±331.39）,（6014.59±291.56）U·L^-1);H₂O₂:（31.98±7.38）,（67.06±18.43）,（86.62±13.41）mmol·L^-1]的水平显著降低,而T-AOC[（7.54±2.51）,（5.80±2.53）,（4.93±2.21）U·mL^-1]水平明显升高（均P<0.05,P<0.01）。结论 TMP对小鼠急性心肌缺血具有保护作用,这可能与降低缺血小鼠心肌酶的水平及防止缺血引起的氧化应激损伤有关。     

佛芍颗粒对功能性腹痛模型小鼠的治疗作用研究

目的 明确佛芍颗粒对功能性腹痛模型小鼠的治疗作用,为临床应用提供基础研究数据支持。方法 实验小鼠按体质量随机分为正常对照组、模型对照组、吗丁啉对照组(12 mg·kg^-1)、四逆散对照组(3 g·kg^-1)、佛芍颗粒高剂量组(48 g生药·kg^-1)、佛芍颗粒中剂量组(24 g生药·kg^-1)、佛芍颗粒低剂量组(12 g生药·kg^-1)7组,每组10只,雌雄各半。采用寒冷刺激结合腹腔注射福尔马林制备寒凝气滞功能性腹痛病证结合模型,通过检测小鼠疼痛潜伏期、疼痛时长、疼痛发生率及结肠组织病理变化等指标综合评价佛芍颗粒对功能性腹痛小鼠的治疗作用。结果 佛芍颗粒可以明显延长疼痛潜伏期(P<0.05,P<0.01)、缩短疼痛持续时间、降低疼痛发生率,减轻小鼠结肠黏膜增生及炎症等。结论 佛芍颗粒可以改善寒冷刺激结合福尔马林诱导的寒凝气滞功能性腹痛病证结合模型小鼠的腹痛,为佛芍颗粒的临床应用提供参考。     

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.