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1.
吴茱萸次碱对小鼠溃疡性肠炎的治疗作用   总被引:4,自引:0,他引:4  
目的:观察吴茱萸次碱治疗小鼠急性结肠炎的药效及对豚鼠肠道平滑肌运动的影响。方法:2,4-二硝基氯苯(DNCB)/乙醇灌肠制作小鼠急性结肠炎模型,经口给予吴茱萸次碱10、30、100 mg·kg-1,观察吴茱萸次碱对小鼠腹泻,组织形态损伤,结肠组织PGE2含量、MPO活力以及对乙酰胆碱、组胺作用下豚鼠离体肠管收缩运动的影响。结果:DNCB诱发结肠炎后,小鼠出现腹泻、充血、溃疡、肠壁增厚等变化。经口给予吴茱萸次碱后,可以显著改善小鼠的腹泻、组织损伤,并且能够降低结肠组织中MPO活性和PGE2的含量,对乙酰胆碱及组胺作用下豚鼠离体肠管收缩亦表现出显著的对抗作用。结论:吴茱萸次碱可以抑制炎性浸润、渗出和组织增生,减轻结肠黏膜的病理损害和抑制肠道平滑肌运动,对实验性动物急性结肠炎有较好的治疗作用。  相似文献   

2.
游宇  刘玉晖  卢放根  孟君 《中南药学》2007,5(4):295-299
目的观察N-乙酰半胱氨酸(NAC)灌肠对小鼠急性溃疡性结肠炎的作用。方法5%葡聚糖硫酸钠(DSS)自由饮用7 d诱导小鼠急性溃疡性结肠炎,同时予以生理盐水(NS)、5-氨基水杨酸(5-ASA)、NAC保留灌肠,观察小鼠体重、粪便性状、隐血便血,计算疾病活动度(DAI)积分,检测结肠长度、结肠过氧化物酶(MPO)活性、血清过氧化物歧化酶(SOD)活力和丙二醛(MDA)含量及肠黏膜病理改变。结果NAC组小鼠隐血、便血、体重下降、DAI积分、病理改变等均好于模型组、NS组(P<0.05),与5-ASA组疗效相似。NAC组SOD活力高于模型组,MPO活性、MDA含量则低于模型组(P<0.05)。结论NAC对DSS诱导的小鼠急性溃疡性结肠炎黏膜损伤有保护作用,其机制可能与抗氧化应激有关。  相似文献   

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巴柳氮对2,4-二硝基氯苯诱导的大鼠实验性结肠炎的作用   总被引:1,自引:0,他引:1  
目的:观察巴柳氮对2,4-二硝基氯苯(DNCB)诱导的大鼠实验性结肠炎的作用,探讨其可能的作用机制。方法:60只大鼠随机分为对照组、模型组及治疗组,采用DNCB法建立大鼠实验性结肠炎的免疫模型,治疗组予巴柳氮灌胃(600 mg·kg~(-1)·d~(-1))治疗。观察3组大鼠结肠组织大体损伤、黏膜病理及白细胞介素2(IL-2)、白细胞个素6(IL-6)含量的变化。结果:巴柳氮治疗组大鼠疾病活动指数(DAI)评分、结肠大体损伤评分硬组织学损伤评分与模型组比较均显著下降(P<0.01),结肠黏膜及血清中IL-2含量与模型组比较显著上升(P<0.01),IL-6含量明显减少(P<0.01)。结论:巴柳氮能有效改善实验性结肠炎大鼠的临床症状,缓解病理学损伤,其治疗机制之一可能是通过增加IL-2的含量、减少IL-6的含量来实现的。  相似文献   

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目的探究龙胆苦苷对结肠炎小鼠的治疗作用。方法采用2,4,6-三硝基苯磺酸(TNBS)-乙醇溶液诱导结肠炎小鼠模型,测定龙胆苦苷给药后对小鼠体质量、结肠指数、胸腺质量、结肠组织中髓过氧化物酶(MPO)活性以及血清炎症细胞因子TNF-α和IL-8的影响,并通过免疫组化法观察龙胆苦苷对小鼠结肠组织中环氧合酶-2(COX-2)蛋白表达的影响。结果给药1周后,龙胆苦苷各剂量组小鼠体质量与模型组相比显著改善;小鼠结肠指数、结肠组织中MPO活性以及炎性细胞因子TNF-α和IL-8与模型组相比均显著降低(P<0.05);免疫组化结果显示,龙胆苦苷能降低结肠炎小鼠组织中环氧合酶-2(COX-2)的蛋白表达。结论龙胆苦苷能修复TNBS-乙醇溶液诱导的小鼠结肠损伤,对小鼠结肠炎有显著的治疗作用。  相似文献   

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甘草甲醇提取物FM100对小鼠溃疡性结肠炎的药效学研究   总被引:1,自引:0,他引:1  
目的观察甘草甲醇提取物FM100对小鼠溃疡性结肠炎的作用。方法用三硝基苯磺酸钠(TNBS)和乙醇制造小鼠溃疡性结肠炎模型,空白对照组和TNBS模型组灌胃等容量生理盐水,阳性对照组灌胃地塞米松0.2mg/kg,FM100大、中、小剂量组分别灌胃FM100300mg/kg、200mg/kg、100mg/kg,连续灌胃14d。观察小鼠体质量变化、腹泻、结肠黏膜组织形态学、脾脏指数及髓过氧化物酶(MPO)活力等指标。结果甘草甲醇提取物FM100可不同程度地改善TNBS/乙醇所致溃疡性结肠炎小鼠体质量下降和腹泻症状,明显降低结肠黏膜粘连及其溃疡分值和脾脏指数,但可增高MPO活力(P<0.05或P<0.01)。结论甘草甲醇提取物FM100对小鼠溃疡性结肠炎有较好的改善作用,能减轻结肠局部的病理性损伤。  相似文献   

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目的:初步评价木樨草素的抗炎作用与机制。方法:采用小鼠足肿胀、肉芽肿和气囊肿模型,考察木樨草素对急、慢性和渗出性炎症的作用;采用脾淋巴细胞增殖实验,观察木樨草素对小鼠的免疫反应的影响;通过人全血分析实验,考察木樨草素对环氧合酶(COX)活性的影响。结果:木樨草素对上述三种炎症反应均有明显抑制作用;能够显著抑制刀豆蛋白A(ConA)刺激引起的小鼠脾细胞增殖,且呈浓度依赖性;对全血COX-1活性无明显影响,但可以显著抑制COX-2的活性。结论:木樨草素可以明显抑制急、慢性炎症反应,其作用机制可能与其对COX-2活性的抑制有关.  相似文献   

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目的探讨牡荆素对葡聚糖硫酸钠(dextran sulfate sodium,DSS)诱导的小鼠溃疡性结肠炎(ulcerative colitis,UC)的药效作用及机制。方法将C57BL/6小鼠随机分成3组(n=10):正常对照组、模型组(4%DSS)和牡荆素组(4%DSS+牡荆素,50 mg·kg-1)。除正常对照组外,其他组小鼠饮用水中加入4%DSS造模,造模同时牡荆素灌胃给药,每天1次,并每天称重和观察血便等症状,直到实验结束。于造模7 d处死小鼠,截取结肠做HE染色并进行组织损伤和炎性细胞浸润评分;ELISA方法检测小鼠结肠黏膜髓过氧化物酶(myeloperoxidase,MPO)活性;反转录荧光定量PCR方法检测小鼠结肠组织肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)、白介素6(interleukin-6,IL-6)及环氧合酶-2(cyclooxygenase 2,COX-2)mRNA的表达水平。结果与正常对照组相比,模型组小鼠体重明显减轻,组织病理评分增高,同时结肠匀浆MPO水平明显升高,结肠组织TNF-α、IL-6和COX-2表达升高。与模型组比较,牡荆素组小鼠上述指标明显改善。结论牡荆素能有效减轻小鼠实验性溃疡性结肠炎,缓解炎症反应,其机制可能与抑制中性粒细胞浸润和减少炎症因子释放有关。  相似文献   

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实验性结肠炎中氧化过度及褪黑素的保护作用   总被引:3,自引:0,他引:3  
目的 探讨褪黑素对大鼠免疫性结肠炎的影响及有关机制。方法 应用三硝基苯磺酸和乙醇制备大鼠免疫性结肠炎模型。实验设正常对照组、模型对照组、阳性药物对照组 (5 氨基水杨酸 ,1 0 0mg·kg- 1 )、褪黑素给药组 (2 5 ,5 0 ,1 0 0mg·kg- 1 ) ,每天灌肠给药 1次 ,给药时间从制备模型 1wk后开始至实验结束共 3wk。观察大鼠结肠黏膜损伤指数 (CMDI)、粪便隐血实验 (OB)、髓过氧化物酶 (MPO)含量和黏膜病理组织学 (HS)情况 ,并检测结肠组织丙二醛(MDA)、谷胱甘肽过氧化物酶 (GSHPx)、过氧化氢酶(CAT)、超氧化物歧化酶 (SOD)、血浆和结肠组织一氧化氮(NO)含量。结果 模型组大鼠结肠CMDI、HS、OB程度和MPO水平均比正常组升高 ,褪黑素可改善结肠炎大鼠CM DI和HS ,降低MPO水平和粪便OB程度 ,改善结肠黏膜病理损伤 ,大鼠结肠MDA、血浆和结肠NO含量增加 ,结肠SOD、GSHPx和CAT水平降低 ,MT可降低MDA、NO含量 ,增加GSHPx、SOD和CAT水平。结论 MT对大鼠结肠黏膜损伤具有保护作用  相似文献   

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黄连解毒汤对大鼠结肠炎组织损伤的影响   总被引:3,自引:0,他引:3  
目的研究黄连解毒汤对实验大鼠结肠炎组织损伤的保护作用及其机制。方法用Wirst大鼠建立结肠炎动物模型,灌服用药2周后,取结肠组织评价大鼠结肠黏膜损伤指数(CMDI),检测结肠髓过氧化物酶(MPO)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH—PX)活性及丙二醛(MDA)的含量。结果不同剂量黄连解毒汤(10、30、50ml/kg体重)灌胃用药后均能不同程度降低模型大鼠结肠黏膜损伤指数(CMDI)和MPO活性、减少MDA含量,提高SOD、GSH—PX活性,且与用药剂量呈一定量效关系。结论黄连解毒汤通过抗脂质过氧化,对大鼠结肠炎结肠损伤进行修复,减轻结肠损伤,抑制结肠炎大鼠炎症反应。  相似文献   

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MT对大鼠乙酸性结肠炎的影响及有关机制初探   总被引:11,自引:1,他引:10  
目的 探讨褪黑素对大鼠乙酸性结肠炎的影响及有关机制。方法 制备大鼠乙酸性结肠炎模型 ,实验设正常对照组、模型对照组、阳性药物对照组 (5 氨基水杨酸 ,10 0mg·kg-1)、MT给药组 (2 5 ,5 0 ,10 0mg·kg-1) ,采用灌肠方式给药 ,每天 1次 ,给药时间从制备模型 2 4h后开始至实验结束共 7d ,正常及模型对照组均给予生理盐水灌肠。实验结束后观察大鼠结肠粘膜损伤指数 (CMDI)、粪便隐血实验(OB)、髓过氧化物酶 (MPO)含量和粘膜病理组织学 (HS)情况 ,并检测结肠组织丙二醛 (MDA)、谷胱甘肽过氧化物酶(GSH Px)、过氧化氢酶 (CAT)、超氧化物歧化酶 (SOD)、一氧化氮 (NO)含量。结果 乙酸性结肠炎大鼠结肠CMDI、HS、OB程度和MPO水平均比正常组明显升高 ,MT灌肠可减轻乙酸性结肠炎大鼠的CMDI和粪便OB程度 ,降低MPO水平 ,10 0mg·kg-1MT可改善结肠粘膜病理损伤。同时可见模型组大鼠结肠组织MDA、NO含量增加 ,SOD、GSH Px和CAT水平降低。MT可明显降低MDA、NO含量 ,增加GSH Px、SOD和CAT水平。结论 MT对乙酸性结肠炎大鼠结肠粘膜损伤具有保护作用  相似文献   

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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.
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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.  相似文献   

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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.  相似文献   

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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.  相似文献   

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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.  相似文献   

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