瑞香素对佐剂性关节炎大鼠滑膜组织的影响

目的:观察瑞香素对佐剂性关节炎(AA)大鼠膝关节滑膜组织和滑液细胞形态学的影响。方法:采用弗式完全佐剂造成大鼠AA模型,造模后d 7开始给药,连续21 d,测量大鼠足跖肿胀度;最后一次给药后大鼠脱颈椎处死,抽取关节滑液,观察滑液中细胞形态及数量的变化;并取关节滑膜组织做病理检查,观察滑膜细胞增生的情况。结果:瑞香素能显著抑制AA大鼠后足踝关节原发性和继发性肿胀;能抑制膝关节滑液细胞(主要是滑膜细胞、巨噬细胞和淋巴细胞)的过度增生,抑制滑膜组织增生和滑膜细胞下疏松结缔组织充血。结论:瑞香素对AA大鼠具有一定的治疗作用。     

芦丁对大鼠佐剂性关节炎的影响

目的观察芦丁对大鼠佐剂性关节炎(AA)的影响。方法弗氏完全佐剂制作AA大鼠模型,于造模第13天将动物随机分为空白对照组、模型组、双氯芬酸钠10mg·kg-1组及芦丁100和200mg·kg-1剂量组,空白对照组和模型组灌胃给予同体积的质量浓度为5g·L-1的羧甲基纤维素钠(CMC-Na),各组大鼠灌胃给药,每日1次,连续15d,观察药物对佐剂性关节炎大鼠原发性病变、继发性病变和体质量变化的影响,并于造模第28天乙醚麻醉处死大鼠,观察各组大鼠血生化(尿素、肌酐、总蛋白、白蛋白及白蛋白/球蛋白比)和血常规(红细胞、白细胞、血红蛋白含量)以及免疫器官(脾脏、胸腺)等指标的变化。结果芦丁100和200mg·kg-1剂量组能显著减轻模型鼠左后足关节肿胀程度(P<0.05),降低胸腺和脾脏系数(P<0.05),降低造模后大鼠血液中升高的白细胞和肌酐的含量(P<0.05)。10mg·kg-1双氯芬酸钠也表现出显著的抗炎和抗关节炎的活性(P<0.01)。结论芦丁100和200mg·kg-1剂量组对弗氏完全佐剂诱导的大鼠AA具有抗炎和改善肾脏功能的作用,且对免疫器官脾脏和胸腺具有保护作用,研究确证芦丁具有一定的抗关节炎活性。     

木瓜苷对大鼠佐剂性关节炎的治疗作用

目的　研究木瓜苷对佐剂性关节炎 (AA)大鼠的治疗作用及部分机制。方法　大鼠足跖皮内注射弗氏完全佐剂诱发大鼠AA模型 ;足容积法测量继发侧足肿胀度 ,进行疼痛评分和多发性关节炎评分 ,MTT法检测胸腺T淋巴细胞和脾脏B淋巴细胞的增殖反应以及腹腔巨噬细胞产生IL 1水平 ,放射性免疫法测定腹腔巨噬细胞产生TNFα 和PGE2含量。结果　大鼠免疫后d 17开始分别灌胃木瓜苷 30、6 0、12 0mg·kg-1和阿克他利 6 0mg·kg-1对照药 ,连续给药 8d。木瓜苷 6 0、12 0mg·kg-1于d 2 1、d 2 4降低AA大鼠继发侧关节肿胀度、关节疼痛评分、多发性关节炎指数 ;木瓜苷 12 0mg·kg-1恢复AA大鼠胸腺T淋巴细胞增殖能力 ;木瓜苷各剂量还可不同程度抑制AA大鼠腹腔巨噬细胞产生IL 1、TNFα 和PGE2 。结论　木瓜苷可减轻AA大鼠关节肿胀、疼痛和多发性关节炎程度 ;该作用可能与调节T淋巴细胞的功能 ,抑制腹腔巨噬细胞过度分泌炎性细胞因子有关     

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。     

草乌甲素对大鼠佐剂性关节炎的影响

目的:了解草乌甲素对佐剂性关节炎(AA)大鼠原发性关节炎的抗炎镇痛作用。方法:用Freund's完全佐剂免疫Wistar大鼠建立AA动物模型,将其随机分为3组,即草乌甲素治疗2组(剂量分别为100μg.kg-1、50μg.kg-1)、注射用水组。于AA动物模型建立当天对实验大鼠进行处理,连续7d,并记录各组大鼠体重、右踝关节周径变化。治疗结束当天记录炎侧踝关节屈关节疼痛试验评分,用ELISA法检测大鼠血清的TNF-α、INF-γ、PGE2、β-内啡肽含量。结果:在100μg.kg-1治疗组中,草乌甲素在治疗第2天即可明显减轻关节肿胀(P<0.05),提高AA大鼠痛阈(p<0.05),显著降低AA大鼠PGE2含量、提升血清β-内啡肽含量(P<0.01);在50μg.kg-1治疗组中,草乌甲素从治疗的第3天起开始减轻关节肿胀(P<0.05),对大鼠PGE2含量、提升血清β-内啡肽含量作用较弱(P>0.05)。100μg.kg-1、50μg.kg-1草乌甲素均可降低AA大鼠血清TNF-α含量(P<0.01),但两者间无统计学差异;草乌甲素对血清INF-γ无明显影响(P>0.05)。结论:草乌甲素明显改善AA大鼠关节的肿胀,这可能与其降低血清TNF-α、PGE2含量有关;草乌甲素提高AA大鼠痛阈可能与降低血清PGE2,提升血清β-内啡肽有关。     

TNF受体封闭肽对大鼠佐剂性关节炎的影响

目的　观察肿瘤坏死因子 (TNF)受体封闭肽对大鼠佐剂性关节炎的影响。方法　注射弗氏完全佐剂建立大鼠佐剂性关节炎模型 ,在关节局部注射TNF受体封闭肽 ,观察对大鼠关节肿胀度、关节组织病理改变及腹腔巨噬细胞表达IL 1βmRNA和TNF αmRNA(RT PCR)的影响。 结果　建立了与人类类风湿性关节炎极其相似的大鼠佐剂性关节炎模型 ;TNF受体封闭肽治疗 10d后 ,大鼠踝关节肿胀完全受到抑制 ;关节组织内炎症细胞浸润减少 ,炎性病理损伤明显减轻 ;大鼠腹腔巨噬细胞表达的TNF αmRNA和IL 1βmRNA明显减低。 结论　TNF受体封闭肽通过抑制佐剂性关节炎TNF α和IL 1的产生 ,而发挥抗炎作用 ,明显减轻关节的病理性损伤 ,有效抑制关节炎的临床进程。     

TNF受体封闭肽对大鼠佐剂性关节炎的影响

目的观察肿瘤坏死因子(TNF)受体封闭肽对大鼠佐剂性关节炎的影响。方法注射弗氏完全佐剂建立大鼠佐剂性关节炎模型,在关节局部注射TNF受体封闭肽,观察对大鼠关节肿胀度、关节组织病理改变及腹腔巨噬细胞表达IL-1β mRNA和TNF-α mRNA(RT-PCR)的影响。结果建立了与人类类风湿性关节炎极其相似的大鼠佐剂性关节炎模型;TNF受体封闭肽治疗10 d后,大鼠踝关节肿胀完全受到抑制;关节组织内炎症细胞浸润减少,炎性病理损伤明显减轻;大鼠腹腔巨噬细胞表达的TNF-α mRNA和IL-1β mRNA明显减低。结论TNF受体封闭肽通过抑制佐剂性关节炎TNF-α和IL-1的产生,而发挥抗炎作用,明显减轻关节的病理性损伤,有效抑制关节炎的临床进程。     

大蒜素对大鼠佐剂性关节炎的作用

目的研究大蒜素(allicin)对大鼠佐剂性关节炎(adjuvant arthritis,AA)的作用,并初步探讨其作用机制。方法采用AA模型,检测大鼠致炎后体重变化及足爪肿胀度,石蜡切片HE染色对关节组织作病理检查,MTT法检测脾淋巴细胞增殖反应,Western-blot法检测关节软组织中环加氧化酶-2(cyclooxygenase-2,COX-2)和诱导性一氧化氮合酶(induced-nitric oxide synthase,iNOS)蛋白的表达,EIA法测定关节软组织中前列腺素E2(Prostaglandin E2,PGE2)水平,NO试剂盒检测关节软组织中NO的含量。结果大蒜素(6、12mg·kg-1)腹腔注射给药能剂量依赖性的减轻AA大鼠的关节炎症,抑制AA大鼠ConA诱导的脾淋巴细胞增殖反应,下调AA大鼠踝关节软组织中高水平COX-2和iNOS蛋白的表达,并降低关节软组织中PGE2水平和NO含量。同时病理检查发现大蒜素可抑制AA小鼠滑膜增生,减轻炎性细胞浸润。结论大蒜素对AA大鼠具有保护作用,其初步机制与其调节免疫、抑制COX-2、iNOS及其他炎症介质表达有关。     

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。     

佐剂性关节炎大鼠细胞免疫功能的变化

类风湿性关节炎(Rheumatoid Arthritis,RA)是一类严重危害人类身体健康的常见自身免疫性疾病.佐剂性关节炎(Adjuvant Arthritis, AA)大鼠是研究类风湿性关节炎(RA)及评价防治RA药物的常用动物模型之一,其病理表现与RA有一定的相似之处,如病变关节肿胀,细胞免疫功能异常等[1],但其免疫病理特征及发病机制目前仍不十分清楚.本实验研究了佐剂性关节炎大鼠的细胞免疫功能变化,探讨细胞免疫功能在大鼠佐剂性关节炎发病机制中的作用.     

Effects of taurochenodeoxycholic acid on adjuvant arthritis in rats

Taurochenodeoxycholic acid (TCDCA) is one of the main bioactive substances of animals' bile acid. In this study, we aimed to investigate the anti-arthritic effects and potential mechanism of TCDCA on adjuvant arthritis (AA) in rats. Freund's complete adjuvant (FCA) was used to induce AA in rats. Paw swelling, index of thymus and spleen and body weight growth rate were measured, and polyarthritis index and radiologic changes were observed. The production of TNF-α, IL-1β, IL-6 and IL-10 was detected by ELISA in serum and synoviocytes. mRNA expression of TNF-α, IL-1β, IL-6 and IL-10 was determined by real-time RT-PCR in synovium tissue and synoviocytes. In both prophylactic and therapeutic treatment, TCDCA significantly suppressed paw swelling and polyarthritis index, increased the loss body weight and index of thymus and spleen, and amended radiologic changes in AA rats. The overproduction and mRNA expression of TNF-α, IL-1β and IL-6 were remarkably suppressed in serum and synovium tissue of all TCDCA-treated rats, however, IL-10 was markedly increased in prophylactic treatment. In a definite concentration ranging from 300 μg/mL to 500 μg/mL, TCDCA showed marked inhibition in the overproduction and mRNA expression of TNF-α, IL-1β and IL-6 in synoviocytes in a concentration-dependent manner, but opposite action on IL-10. In conclusion, treatment with TCDCA confers a good anti-adjuvant arthritis activity in rats, which its reparative effects could be mediated via reduction of the protein and mRNA expression of TNF-α, IL-1β and IL-6, and augment of IL-10 in rats.     

蚁附蠲痹颗粒对佐剂性关节炎大鼠T细胞亚群的影响

目的观察蚁附蠲痹颗粒对佐剂性关节炎大鼠外周T细胞亚群的影响。方法采用流式细胞仪检测佐剂性关节炎大鼠外周血中CD3 、CD4 和CD8 T细胞的变化。结果佐剂性关节炎大鼠外周CD3 和CD4 T细胞无明显变化,而CD8 T细胞显著减少,CD4 /CD8 的相对比显著升高,蚁附蠲痹颗粒对外周异常的T细胞亚群有显著的调节作用。结论蚁附蠲痹颗粒对佐剂性关节炎大鼠外周血T细胞亚群紊乱的调节作用,可能是其治疗类风湿性关节炎的主要机理之一。     

Antinociceptive effects of neonatal capsaicin in rats with adjuvant arthritis

Summary Rats were treated with capsaicin (50 mg/kg, SC) either on the second day or on the second and third days of life. A significant attenuation of the responses to noxious stimuli was obtained in the capsaicin treated animals as measured by the hot-plate or paw pressure tests but not by the tail-flick test. Furthermore, neonatal capsaicin produced a significant reduction of response in the formalin test. Capsaicin reduced the reaction latency in rats with adjuvant arthritis as measured by the hot-plate and paw pressure tests, though capsaicin did not alter the overall time course of the response to Freund's adjuvant. Capsaicin also attenuated the weight loss or the decreased ambulatory and rearing behaviour which occurred in the control animals with adjuvant arthritis. It is suggested that neonatal treatment with capsaicin may relieve the responsiveness to longlasting nociceptive stimuli by adjuvant in rats.     

Antioxidant potential of Gaultheria fragrantissima against adjuvant induced arthritis in Wistar rats

Adjuvant arthritis is one of the extensively used models of chronic inflammatory joint disorder such as rheumatoid arthritis. It is postulated that oxidative stress plays a pivotal role in rheumatoid arthritis. The current research was designed to examine the antioxidative effect of Gaultheria fragrantissima Wall. (Ericaceae) against complete Freund’s adjuvant induced arthritis. Arthritis was induced by single subcutaneous injection of complete Freund’s adjuvant (0.1?mL) into the plantar surface of the right hind paw of male Wistar rats. Gaultheria fragrantissima leaf extracts (100 and 200?mg kg^?1day^?1) and indomethacin (3?mg kg^?1day^?1) were administered orally for 14 days (from day 14 to day 28) after the adjuvant injection. The protective effect was evaluated by DPPH radical scavenging activity, alterations in paw volume, lipid peroxidation (measured in terms of MDA), antioxidant, enzymatic (SOD, CAT, GPx, GR and GST), nonenzymatic (GSH), and marker enzymes (AST, ALT, ALP and GGT) levels from liver and serum of adjuvant induced and treatment groups. These biochemical alterations were significantly (p?<?0.05) ameliorated nearly to control values after administration of Gaultheria fragrantissima leaf extract to arthritic animals.     

Inhibition of adjuvant arthritis by salbutamol and aminophylline

Salbutamol (3 mg/kg) and aminophylline (75 mg/kg) were administered s.c. to rats separately or in combination after intradermal injection of adjuvant into the left hind paw. The paw volume was measured plethysmographically; tissue cyclic AMP content was determined by a protein binding assay following whole body microwave irradiation. The combination of salbutamol and aminophylline given daily significantly inhibited the swelling response in both the adjuvant-injected and the non-injected paws. This drug combination significantly increased the cyclic AMP levels in inflamed tissue of the adjuvant-injected hind paw and in lymphoid tissue such as the spleen and thymus. The combined treatment seems to have immunosuppressive as well as anti-inflammatory effects on adjuvant-induced arthritis.     

紫草素对激素诱导骨质疏松大鼠骨代谢的治疗机制研究

目的探讨紫草素( SKN)对骨质疏松大鼠骨代谢的治疗机制。方法 2022年 1―6月通过糖皮质激素诱导大鼠骨质疏松症,采取腹腔注射紫草素对大鼠进行治疗,通过腹腔注射 shRNA-前蛋白转化酶枯草溶菌素( PCSK5)敲低大鼠体内 PCSK5水平。骨密度仪测量大鼠股骨骨密度( BMD)酶联免疫吸附测定( ELISA)大鼠血清骨钙素( BGP)及 Ⅰ型胶原羧基末端肽(CTX),实时荧光定量 PCR(qRT-PCR)检测大鼠股骨,组织 PCSK5信使 RNA(mRNA)水平,免疫共沉淀验证 PCSK5与生长分化因子 11(GDF11)蛋白相互作用,蛋白质印迹法检测大鼠股骨组织 GDF11蛋白水平。结果与磷酸缓冲盐溶液( PBS)组( 0.23±0.01)g/ cm2比较,糖皮质激素使得糖皮质激素性骨质疏松症( GIOP)(0.12±0.01)g/cm2 BMD值降低( P<0.05),GIOP+二甲亚砜( DMSO)组( 0.11±0.01)g/cm2较 GIOP+SKN组( 0.18±0.01)g/cm2相比BM组D值降低( P<0.05); PBS组 PCSK5 mRNA表达水平量显著低于 GIOP组( 1.01±0.01比 0.23±0.02,P<0.05)GIOP+DMSO显著低于 GIOP+SKN组( 0.24±0.01比 0.81±0.16,P<0.05),GIOP+DMSO+ si-NC组显著高于 GIOP+DMSO+si-PCSK5组,(0.82±0.06比 0.38±0.03,P<0.05); PBS组 GDF11表达量显著低于 GIOP组( 0.30±0.01比 1.22±0.11,P<0.05),GIOP+DMSO组显著高于 GIOP+SKN组(1.28±0.11比 0.52±0.04,P<0.05)GIOP+DMSO+si-NC组显著低于 GIOP+DMSO+si-PCSK5组( 0.49±0.04比 0.87±0.16,P<0.05)。结论紫草素调控 PCSK5/GDF11路促进骨质疏松大鼠骨通,代谢。     

Effects of sorafenib on fibroblast-like synoviocyte apoptosis in rats with adjuvant arthritis

Rheumatoid arthritis (RA) is a chronic autoimmune disease that is characterized by synovial inflammation and hyperplasia resulting from an imbalance between the proliferation and apoptosis of fibroblast-like synoviocytes (FLSs). Our previous study found that sorafenib had inhibitory effects in rats with adjuvant arthritis (AA). The present study investigated the role of sorafenib in the induction of AA FLS apoptosis in vitro. FLSs obtained from AA rats were cultured in vitro and identified. Cell apoptosis was detected using terminal deoxyribonucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) and annexin V-fluorescein isothiocyanate (FITC) and propidium iodide (PI) labeling methods. Real-time PCR and Western blotting assays were used to quantify the expression levels of Fas, Caspase-3, Mcl-1, NF-κB and C-jun gene products in AA FLSs. Our data revealed that sorafenib (4 μmol/L) induced apoptosis in AA FLSs, and flow cytometry analysis showed that AA FLSs treated with sorafenib (4 μmol/L) in vitro accumulated in early and late apoptosis. There were significant increases in the expression levels of Fas, Caspase-3 and Mcl-1, and significant decreases in NF-κB and C-jun expression in AA FLSs treated with sorafenib. In summary, these results demonstrate that sorafenib promotes AA FLS apoptosis, which may be related to the upregulation of Fas and Caspase-3 and downregulation of NF-κB and C-jun. All of these findings suggest that sorafenib exerts an inhibitory effect on AA rats in vivo via AA FLS apoptotic induction, which has potential therapeutic implications for RA.     

克班宁透皮贴剂对佐剂性关节炎大鼠的抗炎作用

目的：考察克班宁制备成透皮贴剂后对佐剂性关节炎大鼠的抗炎作用。方法：将60只雄性Wistar大鼠随机分为6组,分别为正常组、模型组、甲氨蝶呤（MTX）组、克班宁贴剂低、中、高剂量组,每组10只。除正常组外,其余大鼠右后足趾皮下注射0.1 mL弗氏完全佐剂（CFA）造模,给药组于腹部脱毛区域给予克班宁透皮贴剂,MTX组腹腔注射给予甲氨蝶呤,正常组、模型组给予空白透皮贴剂,隔天给药1次,连续给药20 d。观察各组大鼠体质量、关节肿胀度、关节炎指数和免疫器官指数的变化,检测血清中肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）和白细胞介素-6（IL-6）水平,苏木素伊红（HE）染色观察大鼠踝关节病理变化情况。结果：与正常组相比,模型组体质量增长较慢,关节炎指数明显升高,右后肢关节严重肿胀,血清TNF-α、IL-1β和IL-6水平显著升高（P<0.01）,踝关节可见严重滑膜炎症、软骨侵蚀及骨破坏。与模型组相比,各给药组大鼠体质量增加较快,关节肿胀度降低（P<0.01）、关节炎指数降低（P<0.01）,血清中TNF-α、IL-1β、IL-6水平降低（P<0.01）,踝关节炎细胞浸润减轻,软骨破坏减弱。结论：克班宁透皮贴剂能明显改善佐剂性关节炎大鼠关节炎症和病理损伤,降低血清中炎症因子水平,说明克班宁透皮贴剂对佐剂性关节炎具有一定的治疗作用。