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1.
目的 观察隐丹参酮对慢性不可预见应激(CUMS)联合脂多糖(LPS)所致抑郁小鼠氧化应激和炎症反应的影响。方法 60只清洁级ICR小鼠随机分为对照组、模型组、帕罗西汀组(20 mg/kg)及隐丹参酮低、中、高剂量(10、20、40 mg/kg)组,每组10只。采用CUMS+LPS应激刺激14 d建立抑郁模型(除对照组),同时ig相应药物或生理盐水,1次/d,连续14 d。通过体质量增量、糖水偏好指数、悬尾实验及新奇环境摄食测试评价抑郁行为,并测定各组血清超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、谷胱甘肽过氧化物酶(GSH-Px)、丙二醛(MDA),海马和皮质白细胞介素(IL)-6、IL-1β、肿瘤坏死因子(TNF)-α变化情况。结果 隐丹参酮20、40 mg/kg组体质量增量及SOD、CAT、GSH-Px酶活性高于模型组,不动时间短于模型组(P<0.05、0.01),海马IL-6、海马和皮质IL-1β含量低于模型组(P<0.05、0.01)。各治疗组糖水偏好指数高于模型组、摄食潜伏期短于模型组(P<0.05、0.01),血清MDA、皮质TNF-α含量低于模型组(P<0.05、0.01)。隐丹参酮40 mg/kg组皮质IL-6、海马TNF-α含量低于模型组(P<0.01)。结论 隐丹参酮对CUMS联合LPS致小鼠抑郁症状有改善作用,其机制可能与抑制过强的氧化应激反应与神经炎症反应,并减轻神经元损伤有关。  相似文献   

2.
目的 设计并合成系列4-取代的新型红景天苷衍生物并研究其抗疲劳作用。方法 通过五乙酰基葡萄糖与不同的4-取代苄基酪醇,经过糖苷化、脱乙酰基合成红景天苷衍生物;采用小鼠负重游泳为实验模型,通过观察测定小鼠的负重游泳时间研究合成衍生物的抗疲劳作用。结果 合成了10个新型红景天苷衍生物;小鼠负重游泳实验显示:阳性对照组(红景天苷)和3a-1组(苯乙基-β-D-葡萄糖苷)的小鼠游泳时间明显高于空白对照组(P<0.05),差异有统计学意义;其余组均与空白对照组小鼠负重游泳时间相近,差异无统计学意义。结论 本实验设计的红景天苷衍生物合成方法简便、可行;红景天苷及其衍生物苯环上的4位羟基可能与其抗疲劳活性密切相关。  相似文献   

3.
目的 评价湖北金粟兰中倍半萜二聚体化合物(+)-chlorahupetenes B[(+)-CHB]对脂多糖(LPS)诱导的小鼠巨噬细胞(RAW264.7)炎症反应的影响及作用机制。方法 RAW264.7细胞分为对照组(给予等体积DMSO)、模型组(给予等体积DMSO)、地塞米松磷酸钠注射液(Dex,阳性对照,1 μmol·L-1)组和(+)-CHB低、中、高浓度(5、10、20 μmol·L-1)组。各组分别加入相应药物孵育细胞1 h,除对照组外,其余组加入LPS (1 μg·mL-1)诱导24 h造成炎症应答模型。细胞增殖检测法用于评估细胞活力;Griess反应检测一氧化氮(NO)浓度;酶联免疫分析检测炎症细胞因子肿瘤坏死因子α(TNF-α)、白细胞介素(IL)-1β、IL-6的生成;实时荧光定量PCR (qRT-PCR)检测IL-1β、NOD样受体热蛋白结构域相关蛋白3(NLRP3)、环氧合酶-2(COX-2)、诱导型一氧化氮合酶(iNOS)、IL-6TNF-α mRNA表达;Western blotting检测Toll样受体4(TLR4)、髓样分化因子88(MyD88)、核因子κB (NF-κB) p65、p-NF-κB p65、NLRP3、嘌呤能受体(P2X7)蛋白表达水平。结果 与模型组比较,(+)-CHB减少了梭形细胞数量,使大部分细胞恢复正常形态;显著抑制NO、TNF-α、IL-6、IL-1β生成(P<0.01),显著降低COX-2、iNOS、IL-6、TNF-α、NLRP3、IL-1β mRNA水平(P<0.05、0.01);显著降低TLR4、MyD88、NF-κB p65、p-NF-κBp65、NLRP3、P2X7蛋白表达水平(P<0.05、0.01)。结论 (+)-CHB通过抑制TLR4/MyD88/NF-κB信号通路和P2X7/NLRP3/IL-1β炎症小体轴激活缓解LPS诱导的巨噬细胞炎症反应。  相似文献   

4.
目的 探讨橄榄苦苷对脂多糖(LPS)诱导的小鼠腹腔巨噬细胞(RAW264.7)炎症的保护作用及机制。方法 MTT法检测橄榄苦苷(0、10、20、40 μmol/L)对RAW264.7细胞活性的影响;用橄榄苦苷(10、20、40 μmol/L)预处理细胞1 h后,LPS诱导炎症模型,Griess试剂检测细胞内Nitrite释放;Western blotting方法检测细胞iNOS、COX-2、Nrf2、Keap-1、HO-1、NQO1蛋白表达水平;流式细胞仪检测细胞内NO、ROS、Ca2+的水平;荧光显微镜检测线粒体膜电位(MMP)水平;ELISA法检测细胞上清液中肿瘤坏死因子-α(TNF-α)、白介素-6(IL-6)的释放。结果 与模型组比较,橄榄苦苷组Nitrite释放水平显著降低(P<0.05、0.01、0.001),iNOS、COX-2蛋白的表达显著降低(P<0.001),NO的产生显著减少(P<0.05、0.01);TNF-α、IL-6的释放受到显著抑制(P<0.001);Ca2+释放受到显著抑制(P<0.01);ROS生成受到显著抑制(P<0.01);JC-1单体降低,恢复聚合物状态(红色荧光变多),MMP稳定性增强;Keap1蛋白表达显著降低, Nrf2、HO-1、NQO1蛋白的表达均显著升高(P<0.05、0.01、0.001)。结论 橄榄苦苷对LPS诱导的RAW264.7细胞炎症具有抑制作用,其作用机制可能与激活Nrf2/HO-1信号通路相关。  相似文献   

5.
目的 分析莪术油对病毒性脑炎(herpes simplex virus encephalitis,HSE)小鼠TNF-α、TLR2 mRNA和S100B蛋白表达的影响,初步探讨莪术油治疗HSE的相关机制。方法 选择5周龄新西兰小鼠40只,,随机分为空白对照组、莪术油组、单纯疱疹病毒(herpes simplex virus,HSV)-1+莪术油组、HSV-1组;HSV-1组、HSV-1+莪术油组颅内注入HSV-1病毒,造HSE模型小鼠;空白对照组、莪术油组同样方式注射Vero细胞培养液上清;造模后空白对照组、HSV-1组灌胃生理盐水,莪术油组、HSV-1+莪术油组灌胃莪术油。采用免疫组化法对脑组织病理情况进行分析;采用ELISA法检测脑组织中TNF-α、S100B水平;采用QT-PCR法检测脑组织中TLR2 mRNA水平。结果 与HSV-1组相比,HSV-1+莪术油组小鼠可见实质性脑组织细胞变性、水肿减轻,脑组织病灶淋巴细胞、小胶质细胞等单核巨噬细胞侵袭浸润水平减弱,HSV-1+莪术油组小鼠脑组织中TLR2 mRNA水平均显著降低(P<0.01);HSV-1+莪术油组小鼠脑组织中TNF-α及S100B水平均显著降低(P<0.01)。结论 莪术油可能通过抑制病毒性脑炎小鼠TNF-α、TLR2 mRNA、S100B蛋白表达从而发挥疗效。  相似文献   

6.
目的 通过探究左西孟旦对巨噬细胞极化的影响,观察其抗动脉粥样硬化(AS)的作用机制。方法 将45只健康清洁级ApoE-/-小鼠按照数字表法随机分为模型组、左西孟旦(2 mg/kg)组、左西孟旦(2 mg/kg)+脂多糖[LPS,2 mg/kg,Toll样受体4(TLR4)激动剂]组,每组15只,以高脂饲料喂养;取15只健康清洁级C57BL/6小鼠作为对照组,以普通饲料喂养。喂养8周后,ip给药,模型组和对照组ip等体积生理盐水,每天1次,持续4周。全自动生化仪检测血清总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白-胆固醇(LDL-C)及高密度脂蛋白胆固醇(HDL-C)水平;HE染色与Masson染色观察主动脉组织形态变化与纤维化水平,油红O染色检测全主动脉及主动脉根部动脉斑块形成情况;免疫组织化学染色检测主动脉M1型标记蛋白诱导型一氧化氮合酶(iNOS)与M2型标记蛋白分化群206 (CD206)的表达;实时荧光定量 PCR(qRT-PCR)法检测主动脉M1型巨噬细胞相关基因肿瘤坏死因子-α(TNF-α)、白细胞介素(IL-6)与M2型巨噬细胞相关基因转化生长因子-β(TGF-β)、精氨酸-1(Arg-1)的表达;Western blotting检测主动脉TLR4与磷酸化的核转录因子 kB p65(p-NF-κB p65)蛋白表达。结果 与对照组比较,模型组小鼠血清TG、TC和LDL-C水平显著升高,HDL-C水平显著降低(P<0.05);主动脉内膜增厚,斑块面积显著增加,伴随大量纤维化(P<0.05);iNOS阳性细胞比例显著升高,CD206阳性细胞比例显著下降(P<0.05);TNF-α、IL-6 mRNA水平显著上调,TGF-β、Arg-1 mRNA水平显著下调(P<0.05);同时TLR4、p-NF-κB p65蛋白表达显著上调(P<0.05)。与模型组比较,左西孟旦组小鼠血清TG、TC和LDL-C水平显著降低,HDL-C水平显著升高(P<0.05);主动脉病理现象减轻,斑块面积显著减小,纤维化程度显著变小(P<0.05);iNOS阳性细胞比例显著下降而CD206阳性细胞比例显著升高(P<0.05);TNF-α、IL-6 mRNA水平显著下调,TGF-β、Arg-1 mRNA水平显著上调(P<0.05);TLR4、p-NF-κB p65蛋白表达显著下调(P<0.05)。与LPS联用基本抵消左西孟旦对上述病理现象的改善作用。结论 左西孟旦能够抑制TLR4的表达,阻止下游NF-κB信号途径的激活,调控巨噬细胞极化状态,从而发挥抗AS的作用。  相似文献   

7.
张飞  王娟 《现代药物与临床》2019,42(12):2360-2363
目的 探讨核苷酸结合寡聚化结构域样受体蛋白3(NLRP3)在柯萨奇B组3型病毒(CVB3)诱导的病毒性心肌炎中的作用。方法 40只6~8周龄BALB/c雄性小鼠使用随机数字表法随机分为对照组和病毒性心肌炎模型组,每组20只。对照组ip 0.1 mL生理盐水,模型组ip 0.1 mL含有CVB3病毒(1×106 PFU/mL)的病毒液进行造模。造模第7天,处死所有小鼠。酶联免疫吸附法(Elisa)检测血清NLRP3、白介素(IL)-1β和IL-18炎症因子。结果 模型组NLRP3、IL-1β和IL-18表达水平分别为(26.43±4.14)、(31.25±5.63)、(38.57±6.45) μg/L,显著高于对照组的(4.53±1.06)、(6.35±1.24)、(7.83±1.36) μg/L(P<0.01)。模型组心肌炎评分为(2.36±0.27)分,显著高于对照组的(0.18±0.04)分(P<0.01)。模型组心肌细胞NLRP3表达评分为(1.82±0.24)分,显著高于对照组的(0.16±0.03)分(P<0.01)。相关性分析显示模型鼠NLRP3与体质量呈显著负相关(r=-0.517,P<0.05),和心肌炎评分呈显著正相关(r=0.624,P<0.05)。结论 NLRP3炎症小体可能参与了柯萨奇B组3型病毒致小鼠病毒性心肌炎的的发生过程。  相似文献   

8.
目的 探究金丝桃苷(hyperoside,Hyp)对脑缺血再灌注大鼠脑组织的保护作用及相关机制。方法 采用线栓法建立大脑中动脉闭塞/再灌注(middle cerebral artery occlusion/reperfusion,MCAO/R)大鼠模型,分成假手术组、模型组、Hyp低、中、高剂量组(30,60,120 mg·kg-1)。持续给药14 d后,采用Zea Longa法对大鼠进行神经功能评分,并测定脑含水量。TTC染色法测定大鼠脑梗死体积,ELISA检测炎症相关因子,HE染色观察大脑海马CA1区神经元病理形态,TUNEL染色观察大鼠脑组织细胞凋亡程度,Western blotting检测TLR4和COX-2以及凋亡相关蛋白的表达。结果 Hyp干预能够显著改善MCAO/R大鼠Zea Longa评分(P<0.05),减少脑含水量和脑梗死体积,显著降低炎症因子(TNF-α、IL-1β、IL-6、ICAM-1以及VCAM-1)的表达(P<0.05或P<0.01),并且有效改善海马CA1区神经元的病理学改变和凋亡情况,显著抑制TLR4、COX-2、NF-kB、caspase-3、caspase-9以及Bax蛋白的表达(P<0.05或P<0.01),上调Bcl-2蛋白的表达(P<0.05)。结论 Hyp对脑缺血再灌注损伤的保护作用与抗炎、抗凋亡以及抑制TLR4/COX-2信号通路有关。  相似文献   

9.
目的检测淡豆豉炮制过程中各样本γ-氨基丁酸(GABA)含量并研究其抗抑郁作用。方法应用柱前在线衍生-高效液相色谱技术测定原料黑大豆(H)、发酵第6天(F6)、再闷6 d(Z6)、再闷15 d(Z15)样本水煎液中GABA含量;将昆明种小鼠随机分成对照组、模型组、盐酸氟西汀(阳性对照,0.01 g/kg)组、GABA(0.012 8 g/kg)组、H(1.52 g/kg)组、F6(1.52 g/kg)组、Z6(1.52 g/kg)组和Z15低、中、高剂量(0.76、1.52、3.04 g/kg)组,采用单笼饲养加慢性温和不可预知性应激(CUMS)制备小鼠抑郁模型,各组在造模同时开始ig给药,每日应激前1 h给药,连续28 d。检测各组小鼠体质量、糖水偏好、敞箱、悬尾、强迫游泳等行为学指标的变化。结果 H和F6样本水煎液未检出GABA,Z6、Z15样本的GABA质量分数分别为5.559、8.421 mg/g。与对照组比较,模型组小鼠的体质量、糖水偏好、跨格数和直立数均显著减少(P<0.01),悬尾及游泳不动时间显著增加(P<0.05、0.01),表明CUMS抑郁模型制备成功。与模型组比较,盐酸氟西汀组、GABA组、Z6组和Z15高剂量组糖水偏爱度、敞箱实验跨格数和直立数均显著增加(P<0.05、0.01),Z15中剂量组糖水偏爱度和敞箱实验直立数显著增加(P<0.05、0.01);盐酸氟西汀组、GABA组、Z6组及Z15高、中剂量组悬尾实验的不动时间均显著减少(P<0.05、0.01);各组小鼠强迫游泳实验的不动时间均显著缩短(P<0.05、0.01)。结论发现淡豆豉炮制后期出现高含量GABA;淡豆豉显著改善小鼠的快感缺失、行为绝望等抑郁症状,具有良好的抗抑郁作用并与GABA含量可能有关。  相似文献   

10.
目的 探讨延龄草苷(trillin)对小胶质细胞(BV-2)的炎性激活的抑制作用。方法 不同浓度的延龄草苷孵育0.5 h,然后用脂多糖进行刺激,培养24 h后收集上清,Greiss法检测NO浓度;CCK-8检测延龄草苷对小胶质细胞活力的影响;Elisa检测肿瘤坏死因子(TNF-α)的浓度;实时定量PCR(RT-PCR)检测TNF-α、IL-1β、IL-6、iNOS、COX-1、COX-2基因的表达。结果 在不影响细胞活力的前提下,延龄草苷能明显抑制NO的释放,同时能抑制激活诱导细胞死亡,能明显抑制TNF-α的产生,能明显抑制TNF-α、IL-1β、IL-6、iNOS、COX-2 mRNA的表达,但是不能抑制COX-1 mRNA的表达。结论 延龄草苷可以抑制LPS诱导的小胶质细胞的炎性激活,抑制炎性基因的表达。  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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The precocity and efficacy of the vaccines developed so far against COVID-19 has been the most significant and saving advance against the pandemic. The development of vaccines has not prevented, during the whole period of the pandemic, the constant search for therapeutic medicines, both among existing drugs with different indications and in the development of new drugs. The Scientific Committee of the COVID-19 of the Illustrious College of Physicians of Madrid wanted to offer an early, simplified and critical approach to these new drugs, to new developments in immunotherapy and to what has been learned from the immune response modulators already known and which have proven effective against the virus, in order to help understand the current situation.  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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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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