热杀死结核分支杆菌H37Ra诱导的SD大鼠佐剂性关节炎模型研究

目的对热杀死结核分支杆菌H37Ra(Mtb)诱导SD大鼠关节炎模型的血液学、T细胞功能、关节滑膜细胞凋亡及病理变化进行分析,以评价该模型与临床RA类疾病的相似性。方法 SD大鼠尾根部一次性皮下注射Mtb-矿物油诱导剂,定期检测大鼠外周血液常规、血液流变学改变;采用流式细胞术测定外周血淋巴细胞凋亡率及调节性T细胞比例;TUNEL法检测关节滑膜细胞凋亡,镜下观察关节滑膜病理改变。结果 SD大鼠经Mtb免疫后,外周血血红蛋白含量下降,血小板总数、红细胞压积上升,全血黏度、血浆黏度上升;外周血淋巴细胞凋亡率明显降低;CD4+CD25+FOXP3+T细胞占CD4+T细胞的比例、CD4+CD25+T细胞占CD4+T细胞的比例均下降;关节滑膜细胞凋亡减少;关节滑膜组织异常增生,有大量炎性细胞浸润,并有肉芽组织形成。结论由Mtb诱导的SD大鼠佐剂性关节炎模型临床表现及组织学改变与临床RA相似,免疫学指标存在明显的细胞免疫异常;该模型制作方法简单、复制成功率高、经济实用,可广泛用于RA的医学研究及抗RA新药筛选。     

苦参素对佐剂性关节炎大鼠的治疗作用

目的研究苦参素(OM)对大鼠佐剂型关节炎(AA)的影响,并探讨部分作用机制。方法弗氏完全佐剂(FCA)诱导AA大鼠模型,检测大鼠足爪肿胀度、多发性关节炎指数(AI),HE染色观察关节病理学改变,放免法检测血清IL-1β、TNF-α水平。结果 OM(60、120 mg.kg-1)剂量组能明显抑制AA大鼠继发性足肿胀,改善膝关节的病理学病变,使AA大鼠血清IL-1β、TNF-α水平显著下降。结论 OM对AA大鼠有治疗作用,调节体内细胞因子IL-1β、TNF-α的水平可能是其治疗AA的作用机制之一。     

伪麻黄碱水杨酸盐对大鼠佐剂性关节炎及免疫系统的影响

大鼠佐剂性关节炎 (AA)模型病理特征与类风湿性关节炎 (RA)相似 ,这类免疫性炎症模型对研究抗炎、抗风湿药物有重要价值。从麻黄中提取的两种主要生物碱麻黄碱 (左旋麻黄碱 )和伪麻黄碱 (右旋麻黄碱 )其化学结构互为差相异构体。伪麻黄碱具有松驰平滑肌、收缩血管、兴奋中枢神经等作用[2 ] ,因其碱性刺激作用以及易出现快速耐受性 ,未被我国药典收载。水杨酸是较早用于临床的解热镇痛药 ,对炎症细胞的聚集、激活、趋化有抑制作用 ,亦有抑制血小板聚集等功能 ,由于酸性太强 ,口服可引发胃出血而被淘汰 ,将这两种理化性质相反的物质合成新化…     

原花青素对佐剂性关节炎大鼠炎性介质的影响

目的 观察原花青素对佐剂性关节炎大鼠炎症介质PGE2、NO和细胞因子IL—β、TNF—α、IL-4、IL-0的影响。方法60只雄性SD大鼠随机分为正常对照组、模型对照组、地塞米松治疗组（2mg／kg）、原花青素小剂量组（1．2mg／kg）、原花青素中剂量组（6mg／kg）、原花青素大剂量组（30mg／kg），每组10只，以完全弗氏佐剂制造大鼠佐剂性关节炎模型。大鼠于致炎后第8天给药，第24天心脏取血，ELISA测血清中IL—β、TNF—α、IL-4、IL—10的含量；并剪下致炎足的对侧足爪，剪碎后浸泡于生理盐水2小时，     

刺山柑总黄酮对大鼠佐剂性关节炎的药效学研究

目的考察刺山柑总黄酮干预大鼠佐剂性关节炎的作用。方法建立大鼠Freund’s完全佐剂性关节炎模型,以大孔树脂分离得到的总黄酮为供试药品,灌服模型大鼠,并以生理盐水作为对照。造模后一周,采用足趾容积测量仪测定大鼠足趾的肿胀程度;造模后21～28 d,通过关节炎指数评分标准来评价继发性病变的严重性,并通过制备滑膜组织的切片来观察滑膜组织细胞的变化。结果与模型组比较,造模后18 h及5 d内,刺山柑黄酮组大鼠的足趾肿胀度明显降低(P<0.01);其关节炎指数评分与模型组比较均有显著降低,并能有效地保护滑膜组织,降低炎性细胞的浸润。结论刺山柑总黄酮对佐剂性关节炎原发病具有治疗作用,对继发病的预防作用明显。     

青藤碱对佐剂性关节炎大鼠滑膜细胞因子表达的影响

目的:观察青藤碱对佐剂性关节炎大鼠滑膜细胞核因子 κB(NF κB)活性及TNF α mRNA、IL 1β mRNA、IL 10 mRNA的影响,阐明该药治疗类风湿关节炎的可能机制.方法:以佐剂性关节炎大鼠为模型,收集滑膜细胞,采用电泳迁移率改变分析法检测NF κB的活性,反转录 PCR检测TNF α mRNA、IL 1β mRNA、IL 10 mRNA的表达.结果:佐剂性关节炎大鼠滑膜细胞内NF κB活性与TNF α mRNA、IL 1β mRNA、IL 10 mRNA的表达均显著升高,青藤碱在一定的浓度范围内呈浓度依赖性抑制NF κB活性与TNF α mRNA 、IL 1β mRNA的表达,而对IL 10 mRNA的抑制效应与浓度无关.结论:青藤碱可能通过抑制NF κB活性而降低滑膜细胞内TNF α mRNA及IL 1β mRNA的表达.     

京尼平苷酸对佐剂性关节炎模型大鼠滑膜细胞体外培养增殖及分泌细胞因子的影响

目的:研究京尼平苷酸(GA)对佐剂性关节炎(AA)模型大鼠滑膜细胞体外培养增殖能力和分泌细胞因子的影响。方法:用弗氏完全佐剂建立AA模型大鼠,分离其滑膜细胞进行培养,以阳性细胞数和纯度鉴定其免疫细胞;将细胞分为对照组,GA低、中、高(10-7、10-6、10-5mol·L-1)剂量组,阳性对照(甲氨蝶呤,10-6mol·L-1)组并加入相应药物处理。MTT法检测吸光度(A)考察GA对滑膜细胞增殖的影响;流式细胞术测定细胞周期;酶联免疫吸附法检测各组滑膜细胞分泌肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、IL-10的水平。结果:2～3代滑膜细胞纯度达到试验要求;与对照组比较,GA高剂量组和阳性对照组大鼠滑膜细胞A值,S和G2/M期细胞比例,细胞外液TNF-α、IL-1β水平明显降低(P<0.05或P<0.01),G1期细胞比例、IL-10水平明显升高(P<0.05或P<0.01)。结论:GA能显著抑制AA模型大鼠滑膜细胞的增殖,阻滞细胞周期于G1期,抑制滑膜细胞分泌TNF-α和IL-1β,促进IL-10分泌。     

雷公藤内酯醇对大鼠佐剂性关节炎的影响

雷公藤内酯醇０．１￣０．４ｍｇ／ｋｇ ｉｇ对大鼠佐剂性关节炎原发病变和继发性病变的预防和治疗作用均有明显的疗效，能够使注射佐剂右侧足及对侧足（左）关节肿胀明显消退，且能使大鼠前肢红肿、耳部红斑及尾部结节等全身病损比对照组明显减轻。     

新风胶囊对佐剂性关节炎模型大鼠的抗炎作用

目的:研究新风胶囊对佐剂性关节炎(AA)模型大鼠的抗炎作用。方法:取70只SD大鼠随机均分为正常对照组、模型对照(等容生理盐水)组、阳性对照中药[祛风止痛胶囊0.4 g(生药)/kg]组、阳性对照西药(来氟米特片2.1 mg/kg)组和新风胶囊低、中、高剂量[0.8、1.6、3.2 g(生药)/kg]组,依次记为A、B、C、D、E、F、G组,除A组外其余各组大鼠皮内注射弗氏完全佐剂复制AA模型,致炎第12天开始连续ig给药28 d。检测并计算各组大鼠给药前、后足趾肿胀度和关节炎指数,于末次给药24 h后检测各组大鼠血清及关节滑膜组织中白细胞介素1β(IL-1β)、肿瘤坏死因子α(TNF-α)含量并观察踝关节组织病理学形态变化。结果:与A组比较,B组大鼠足趾肿胀度和关节炎指数升高,血清及关节滑膜组织中IL-1β、TNF-α含量增加,差异有统计学意义(P<0.01)。与给药前比较,C、D、E、F、G组大鼠足跖肿胀度和关节炎指数降低,差异有统计学意义(P<0.05)。与B组比较,C、D、E、F、G组大鼠足趾肿胀度和关节炎指数降低,血清及关节滑膜组织中IL-1β、TNF-α含量降低,差异有统计学意义(P<0.01或P<0.05)。B组大鼠踝关节组织出现滑膜增生、炎性细胞浸润;C、D、F、G组大鼠滑膜增生和炎症情况较B组均减轻。结论:新风胶囊对AA模型大鼠具有抗炎作用,其机制可能与促进滑膜细胞凋亡、抑制滑膜增生有关。     

大鼠胶原诱导性关节炎模型的制备及评价

目的:制备型胶原诱导性关节炎大鼠模型(CIA模型)。方法:将40只大鼠随机分为正常组和模型组。以酶联免疫吸附测定法(ELISA法)检测模型组和正常组大鼠血清中炎性细胞因子肿瘤坏死因子-α(TNF-α)水平,同时采用组织病理学和X线摄片的方法显示关节炎大鼠的发病程度和病理学特征。结果:与正常组相比,模型组在免疫后第36天关节肿胀达到最高峰。ELISA法检测结果显示模型组TNF-α的水平均较正常组大鼠明显增高(P<0.05)。组织病理学和X射线摄片结果显示,关节软骨组织、骨组织和滑膜组织呈典型的关节炎病变。结论:胶原诱导的大鼠关节炎模型,其病理特征和人类类风湿关节炎(RA)极为相似,为进一步深入研究人类RA的发病机制及其临床治疗提供了有价值的实验材料。     

The effect of piroxicam on locomotor activity in rats with adjuvant-induced arthritis

To evaluate the effectiveness of piroxicam, a clinically effective, long-acting, nonsteroidal antiinflammatory drug, in a potential animal model of chronic nociception, the locomotor activity of arthritic rats was monitored over long periods of time by computer. Rats injected with complete Freund's adjuvant (CFA) displayed locomotor deficits as measured by both horizontal and vertical activity. In experiment 1, to test the effectiveness of piroxicam therapy in severely arthritic animals, administration of piroxicam (1--10 mg/kg/day) was initiated 14 days after CFA injection and activity was recorded for 5 days. It was found that a single treatment significantly increased the mobility of the arthritic animals and the 4 additional days of treatment induced continued improvement in mobility and reduction in paw swelling. In experiment 2, to assess the effect of piroxicam on the development of the immobility associated with CFA-induced arthritis, piroxicam administration (0.3--3.3 mg/kg/day) was initiated prior to CFA injection and locomotor activity was monitored for 16 days. It was demonstrated that the activity of CFA-injected rats severely and progressively decreased and that piroxicam significantly increased the activity of the arthritic rats, while having no effect on the activity of the nonarthritic control animals. These studies demonstrate the efficacy of piroxicam in arthritic rats and, although further investigation is necessary, demonstrate that the measurement of locomotor activity in arthritic rodents may be an important tool for the identification and evaluation of antiinflammatory/analgetic agents.     

建立支气管哮喘大鼠模型的新方法及评价

目的 探讨建立支气管哮喘动物模型的新方法.方法 20只清洁级SD大鼠随机分为哮喘组和对照组,每组10只,哮喘组以小剂量卵蛋白(OVA)1 mg致敏并激发为大鼠哮喘模型,对照组以氢氧化铝凝胶致敏,以0.9％氯化钠溶液激发.观察2组大鼠肺组织病理、支气管肺泡灌洗液(BALF)细胞分类及血清OVA-specific IgE水...     

茵连痛风颗粒对佐剂性关节炎大鼠的抗炎镇痛作用研究

目的 考察茵连痛风颗粒对佐剂性关节炎大鼠的缓解作用。方法 建立弗氏完全佐剂模型,48只大鼠随机分为正常组、模型组、茵连痛风颗粒高、中、低剂量组（15.4、7.7、3.8 g/kg）,用药物干预后,测定大鼠关节炎指数、踝关节肿胀率、甲醛致痛分值,用ELISA检测IL-4、IL-10、前动力蛋白（PK1,PK2）含量。观察大鼠足趾肉垫病理变化。结果 与模型组比较,茵连痛风颗粒组可显著抑制大鼠踝关节肿胀,降低甲醛致痛反应（P<0.01）,明显升高抑炎因子IL-4、IL-10 含量（P<0.01）,降低PK1、PK2含量（P<0.01）;缓解足趾水肿和淋巴细胞浸润。结论 茵连痛风颗粒对佐剂关节炎具有明显抑制作用,暗示其对类风湿关节炎具有一定的治疗前景。     

Comparison of the stimulus effects of ethylketocyclazocine in fischer and Sprague-Dawley rats

The discriminative stimulus effects of ethylketocyclazocine (EKC) were characterized in Fischer and Sprague-Dawley rats trained to discriminate 0.3 mg/kg of EKC (s. c.) from saline in a two-choice, discrete-trial avoidance paradigm. The putative mu-opioid receptor agonists morphine and fentanyl, as well as the putative kappa-opioid receptor agonists EKC and U50,488H generalized completely with the EKC cue in both strains of rats. Only small quantitative differences between strains were observed in the generalization of these agonists with EKC. However, Sprague-Dawley rats were notably more sensitive than Fischer rats to the depressant effects of fentanyl. Only small quantitative differences between strains were also observed in the dose of naloxone necessary for complete antagonism of the EKC-like stimulus effects of the mu- and kappa-opioid agonists. The mu-opioid agonists were approximately 2–6 times more sensitive to naloxone antagonism than the kappa-opioid agonists in both Fischer and Sprague-Dawley rats. However, due to inter-animal variability, this difference was not statistically significant. The results of this study suggest that one or more opioid receptor subtype(s) may be involved in the production of the EKC cue in both strains of rats.     

Acute and 13 weeks subchronic toxicological evaluation of naringin in Sprague-Dawley rats

Naringin is widely distributed in plant foods and has not previously been evaluated for safety through standard in vivo toxicological studies. In the present study, acute and subchronic oral toxicity studies of naringin were designed and conducted in Sprague-Dawley (SD) rats. Acute oral administration of naringin was done as a single bolus dose up to 16 g/kg and subchronic toxicity study for 13 weeks was done by oral administration at doses of 0 (control), 50, 250 and 1250 mg/kg in SD rats. There were no mortality, adverse clinical signs, abnormal changes in body weights or food consumption, toxicologically relevant changes in hematology, clinical biochemistry and macroscopic findings during 14 days of the acute toxicity study. During the subchronic oral toxicity study, no mortality and toxicologically significant changes in clinical signs, food consumption, opthalmoscopic examination, hematology, clinical biochemistry, serum sex hormone, macroscopic findings, organ weights and histopathological examination except for slight body weight decrease were noted and attributed to naringin administration. These observations suggest that naringin is practically non-toxic for SD rats in oral acute toxicity study and the no-observed-adverse-effect-level (NOAEL) of naringin in rats is greater than 1250 mg/kg/day when administered orally for 13 consecutive weeks.     

佐剂性关节炎大鼠模型的实验研究

目的：改进大鼠佐剂性关节炎(AA)模型制作的实验设计，提高造模成功率。方法：选择影响造模成功率较大的因素，如弗氏完全佐剂(FCA)中的卡介苗(BCG)浓度、FCA注射量、FCA体内注射部位作为研究对象。结果：不同BCG浓度下的最高成功率为78．5％；不同注射量最高成功率为71．9％；不同注射部位最高成功率为70．0％。结论：用含20mg／ml BCG浓度的FCA 0．1ml注射量，后肢足跖皮内注射能明显提高AA大鼠造模的成功率。较以前文献报道的含10mg／ml BCG浓度的FCA 0．05ml注射量，背部多点注射法等有较大的改进。