黄芩苷元对炎症反应的影响

目的研究以黄芩苷元为主要成分的黄芩提取物SBM抗炎作用,并初步探讨其作用机制。方法观察SBM体外对PGE2合成、COX-2酶活性,COX-2蛋白表达、p38蛋白磷酸化的影响;观察给药后对角叉菜胶诱导大鼠足肿胀、醋酸诱导的小鼠扭体反应的影响。结果SBM可抑制LPS诱导腹腔巨噬细胞PGE2合成、COX-2酶活性及COX-2蛋白表达;抑制ConA诱导的小鼠脾淋巴细胞p38蛋白磷酸化;并可抑制角叉菜胶诱导的大鼠足肿胀及醋酸诱导的小鼠扭体反应。结论黄芩提取物SBM可通过抑制淋巴细胞功能、炎症介质产生发挥抗炎作用。     

美洛昔康贴片抗炎作用实验研究

目的观察局部用美洛昔康贴剂(Mel T)的抗炎作用及其对胃肠道的刺激性。方法采用二甲苯致腹腔毛细血管通透性增加法和二甲苯致耳肿胀法,角叉菜胶诱发足肿胀法以及完全佐剂诱导佐剂性关节炎等实验方法。结果Mel T局部粘贴小鼠20、105、mg/kg,明显抑制二甲苯所致的小鼠耳肿胀和二甲苯引起的皮肤毛细血管通透性的增加,大鼠足部粘贴14、7、3.5 mg/kg,明显抑制角叉菜胶致大鼠足肿胀;对AA大鼠原发性和继发性炎症均有抑制作用,且大鼠胃肠道粘膜出血和溃疡比Mel灌胃组少。结论Mel T有明显的抗炎作用,不良反应小于口服给药。     

祛风息痛丸对大鼠佐剂性关节炎的治疗作用

目的观察祛风息痛丸对佐剂性关节炎的治疗作用,为其临床治疗类风湿性关节炎提供实验依据。方法建立佐剂性关节炎大鼠模型,采用玻璃容器法测定大鼠原发性和继发性足爪肿胀度。采用酶联免疫吸附试验测定血清白细胞介素1(IL-1)和肿瘤坏死因子α(TNFα)含量。结果祛风息痛丸0.26,0.78和2.34g.kg-1连续灌胃3d显著抑制佐剂性关节炎大鼠原发性足爪肿胀,对致炎后18h的肿胀抑制率分别为21.4%,36.8%和65.0%。同剂量祛风息痛丸连续灌胃30d对佐剂性关节炎大鼠继发性即非致炎侧关节肿胀具有明显的抑制作用,并可明显降低多发性关节炎病变评分,中、大剂量可明显降低血清IL-1和TNFα含量。结论祛风息痛丸对实验性佐剂性关节炎具有治疗作用。     

威灵仙总皂苷对大鼠佐剂性关节炎抗炎作用的研究

目的通过观察威灵仙总皂苷对佐剂性关节炎大鼠的影响,探讨其抗炎作用。方法利用Freund’s完全佐剂足趾皮内注射致大鼠关节炎,观察威灵仙总皂苷25、50、100 mg.kg-1三种剂量对佐剂性关节炎大鼠原发性病变和继发性足跖肿胀的影响,以及对细胞因子IL-1、IL-6、IL-8、TNF-α和炎症介质PGE2含量的影响。结果威灵仙总皂苷25、50、100 mg.kg-1对佐剂性关节炎大鼠的原发性和继发性足跖肿胀都有显著性作用,同时对IL-1、IL-6、IL-8、TNF-α和PGE2有抑制作用或趋势。结论威灵仙总皂苷对大鼠佐剂性关节炎具有较显著的抗炎作用。     

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。     

重组人肿瘤坏死因子受体融合蛋白治疗大鼠佐剂性关节炎的作用及对巨噬细胞功能的影响

目的:研究重组人肿瘤坏死因子受体融合蛋白(RhTNFR:Fc)对佐剂性关节炎(AA)大鼠模型的治疗作用及对巨噬细胞产生细胞因子的影响。方法:完全弗氏佐剂免疫SD大鼠诱导AA模型,随机分为正常组、模型组、RhTNFR:Fc低、中、高剂量组(1,3,9 mg.kg-1)和阴性对照组(IgG-Fc 9 mg.kg-1)。记录全身评分、关节炎指数、足爪肿胀度、关节肿胀数等整体评价指标、足爪X线摄片、踝关节病理检查及评分,ELISA试剂盒测定腹腔巨噬细胞(PMφ)上清中细胞因子白细胞介素1β(IL-1β),IL-6和肿瘤坏死因子α(TNF-α)水平。结果:RhTNFR:Fc给药组能不同程度地降低AA大鼠升高的全身评分、关节炎指数、足爪肿胀度和关节肿胀数等整体评价指标,减轻AA大鼠的关节炎症,改善AA大鼠X线摄片评分和关节病理学变化,下调PMφ的IL-1β,IL-6和TNF-α的分泌水平。结论:RhTNFR:Fc对大鼠AA的关节炎症具有治疗作用,且抑制腹腔巨噬细胞促炎性细胞因子的表达。     

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     

合成鱼腥草素的抗炎镇痛作用

合成鱼腥草素灌胃给药对巴豆油致小鼠耳肿胀、角叉菜胶致大鼠足肿胀、醋酸致小鼠腹腔毛细血管通透性增高均有显著抑制作用．同时灌胃给药可以抑制醋酸所致的小鼠扭体反应，延长热痛反应潜伏期，拮抗甲醛致痛作用     

雷公藤双层片的抗炎作用

目的　评价雷公藤双层片的抗炎作用。方法　制备大鼠佐剂性关节炎、琼脂所致大鼠足跖肿胀、大鼠巴豆油气囊肿模型,观察雷公藤双层片的作用。结果　雷公藤双层片明显抑制大鼠佐剂性关节炎继发病变,使佐剂性关节炎大鼠脾重量减轻,肾上腺重量增加,血浆皮质醇水平升高,外周血T淋巴细胞显著降低。雷公藤双层片对琼脂所致大鼠足跖肿胀也有明显抑制作用;同时能明显抑制大鼠巴豆油气囊肿的渗出和肉芽组织增生。结论　雷公藤双层片具有显著的抗炎作用,其抗炎作用与它抑制细胞免疫功能及与垂体-肾上腺皮质系统有关。     

橙皮苷对大鼠佐剂性关节炎的治疗作用及机制

目的研究橙皮苷(hesperidin,HDN)对佐剂性关节炎(AA)大鼠的治疗作用及部分机制。方法用弗氏完全佐剂(FCA)诱导大鼠AA模型;足容积法测量继发侧足肿胀度;MTT法检测刀豆蛋白(ConA)和脂多糖(LPS)诱导的脾淋巴细胞增殖反应;放免法测定脾淋巴细胞产生IL-2的水平以及腹腔巨噬细胞(PMΦ)IL-1,IL-6和TNF-α的水平;酶联免疫吸附测定法(ELISA)测定PMΦ产生IL-10的水平。结果致炎后d12,大鼠继发性关节炎出现,同时灌胃给予不同剂量的HDN(40、80、160mg·kg-1),连续12d,从致炎后d20开始,HDN(80、160mg·kg-1)对AA大鼠继发性炎症有明显抑制作用;HDN各剂量可不同程度地纠正AA大鼠低下的脾淋巴细胞增殖反应和脾细胞IL-2的产生,降低AA大鼠PMΦ产生过高的IL-1,IL-6和TNF-α,同时上调AA大鼠PMΦ低下的IL-10水平。结论HDN对AA大鼠继发性炎症具有治疗作用,其作用机制可能与调节机体异常的免疫功能和维持细胞因子网络平衡有关。     

豹皮樟总黄酮对大鼠佐剂性关节炎的作用及部分机制研究

目的研究豹皮樟总黄酮(total flavonoids of Litseacoreana Leve,TFLC)对佐剂性关节炎的治疗作用及其机制。方法采用福氏完全佐剂诱导大鼠佐剂性关节炎(adjuvant-induced arthritis,AA)模型,观察TFLC的抗炎作用;放免法测定AA大鼠腹腔巨噬细胞(peritoneal macrophages,PMΦ)中肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)、白细胞介素6(interleukin-6,IL-6)的含量;MTT法检测AA大鼠脾淋巴细胞增殖反应;HE染色法观察AA大鼠膝关节病理组织学变化;免疫组化法观察AA大鼠膝关节滑膜细胞中基质金属蛋白酶9(matrix metalloproteinases,MMP-9)蛋白表达情况。结果TFLC(50、100、200mg.kg-1)对AA大鼠的原发性、继发性炎症具有明显的抑制作用,降低多发性关节炎评分;TFLC(50、100、200mg.kg-1)可提高AA大鼠低下的脾淋巴细胞增殖反应;TFLC(50、100、200mg.kg-1)有效降低AA大鼠PMΦ产生的TNF-α、IL-6水平;TFLC(50、100、200mg.kg-1)改善AA大鼠膝关节病理损伤;TFLC(50、100、200mg.kg-1)能明显降低AA大鼠膝关节滑膜细胞中MMP-9的蛋白表达。结论TFLC(50、100、200mg.kg-1)对AA大鼠具有明显的治疗作用,抗炎机制可能与调节免疫功能、减少细胞因子的生成以及抑制基质金属蛋白酶的蛋白表达有关。     

Astragaloside IV possesses antiarthritic effect by preventing interleukin 1β-induced joint inflammation and cartilage damage

The saponin astragaloside IV (AST) is one of major active components purified from Astragalus membranaceus (Fisch) Bge, which has been used in traditional Chinese medicine to treat immune disorders including rheumatoid arthritis (RA). The effects of AST on the suppression of experimental arthritis and its possible mechanisms are unknown. We measured the paw swelling of ankle joints, splenocyte proliferation, interleukin 1β (IL-1β), tumor necrosis factor α (TNFα) and nitric oxide (NO) formation by macrophages in rat adjuvant-induced arthritis (AIA). Intraarticular injection of IL-1β to rat knee joint for inducing the edema and in vitro IL-1β-stimulated cartilage impairment were examined. The results showed that oral treatment of AST (100 mg/kg/day) suppressed the joint inflammation and inhibited IL-1β, TNFα and NO production in macrophages from AIA rats. Macrophages were one of AST targeted cells, and mediated the reduced splenocyte proliferation in AIA rats. In addition, AST reduced the swelling induced by intraarticular injection of IL-1β, and protected against IL-1β-induced damage of cartilage proteoglycan synthesis and chondrocyte proliferation. We conclude that AST possesses antiarthritic effect and prevents IL-1β-induced joint inflammation and cartilage destruction. These findings suggest that AST may be used for the treatment of RA and other inflammatory joint diseases.     

The anti-inflammatory and anti-nociceptive effects of ethyl acetate fraction of cynanchi paniculati radix

The anti-inflammatory and anti-nociceptive effects and sedative activities of the ethyl acetate fraction of Cynanchum paniculatum (EACP) were evaluated in mice and rats by acetic acid-induced vascular permeability, arachidonic acid-induced paw edema, cotton pellet-induced granuloma formation, formalin-induced licking time, acetic acid-induced writhing response, and pentobarbital-induced sleeping time. EACP at a dose of 40 mg/kg significantly exhibited anti-inflammatory activities on acetic acid-induced vascular permeability, arachidonic acid-induced paw edema, and the late phase of formalin-induced licking time. Moreover, it showed anti-nociceptive effects on acetic acid-induced writhing responses and significant sedative effects on pentobarbital-induced sleeping time. The results demonstrated that the anti-nociceptive effects are apparently related to the sedative effects of EACP. These results support the use of Cynanchum paniculatum in relieving inflammatory pain.     

猪苓多糖通过Toll样受体4对小鼠腹腔巨噬细胞的活化作用

目的观察猪苓多糖(PPS)对小鼠腹腔巨噬细胞的活化作用,并研究Toll样受体4(TLR4)在其中的作用。方法用PPS12.5,25,50及100mg·L-1刺激C3H/HeN小鼠和TLR4缺陷的C3H/HeJ小鼠脾细胞72h或腹腔巨噬细胞24h,以[3H]TdR掺入法检测脾细胞增殖反应;以Griess法测定腹腔巨噬细胞培养上清一氧化氮(NO)水平,ELISA检测白细胞介素1β(IL-1β)和肿瘤坏死因子α(TNF-α)含量;以溴化氰活化多糖的方法制备荧光胺(Flu)标记的PPS(Flu-PPS)及Flu-葡聚糖,应用流式细胞仪及激光共聚焦显微镜检测Flu-PPS与小鼠腹腔巨噬细胞的结合。结果 PPS可明显促进C3H/HeN小鼠脾细胞增殖并诱导腹腔巨噬细胞分泌NO,IL-1β和TNF-α,且具有浓度依赖性(r=0.999,P<0.01)。用抗TLR4单抗20mg·L-1与C3H/HeN小鼠腹腔巨噬细胞预孵育1h后加入PPS50mg·L-1,与单独PPS50mg·L-1孵育比较,巨噬细胞培养上清IL-1β和TNF-α浓度分别由(0.38±0.06)μg·L-1和(0.29±0.05)μg·L-1降至(0.18±0.01)μg·L-1和(0.12±0.02)μg·L-1,降幅达52.6%和58.6%(P<0.01)。PPS对C3H/HeN小鼠的脾细胞增殖、腹腔巨噬细胞产生IL-1β和TNF-α的作用明显强于C3H/HeJ小鼠:PPS12.5～100mg·L-1组脾细胞增殖分别增加了2.4,1.7,1.5和22.2倍,IL-1β增加了0.9,1.3,1.2和1.1倍,TNF-α增加了1.3,0.9,0.6和0.6倍,差异均有统计学意义(P<0.01)。流式细胞仪及激光共聚焦显微镜分析结果表明,Flu-PPS1mg·L-1与小鼠腹腔巨噬细胞结合的荧光强度显著高于Flu-葡聚糖,增加Flu-PPS浓度至5mg·L-1,荧光强度并未相应增强,表明Flu-PPS与小鼠腹腔巨噬细胞的结合具有饱和性;未标记的PPS100mg·L-1及抗TLR4单抗200mg·L-1可明显阻断Flu-PPS与巨噬细胞的结合。结论 PPS可能通过TLR4活化小鼠腹腔巨噬细胞。     

Pharmacological study on Aconiti Tuber. I. Effect of water extract from Aconiti Tuber on adjuvant-induced arthritis]

Anti-inflammatory activity of a hot water extract (A-ext) of Aconiti Tuber (Aconitum calmicaeli DEBX.) has been studied by using various experimental models. The successive administration of A-ext from the day of injection of adjuvant agent or 5 d after the injection it significantly inhibited the adjuvant-induced arthritis developed in the primary and secondary lesions in rats. However, when A-ext was administered from 11 d after the injection of adjuvant, the arthritic paw edema was not reduced. A-ext did not inhibit an acetic acid-induced increase in vascular permeability in mice and carrageenin-induced paw edema in rats. A-ext inhibited cotton pellet-induced granuloma in rats, but did not suppress the weight of thymus and adrenal gland. In vitro experiment, A-ext contracted the isolated ileum of guinea pig, but the contractive activity was reduced by pretreatment of anti-histamine agent, diphenhydramine, but not by pretreatment of papaverine or atropine. A-ext did not release histamine from peritoneal mast cell. These results suggest that A-ext prevents the adjuvant-induced arthritis and has a histamine-like effect.     

Isofraxidin exhibited anti-inflammatory effects in vivo and inhibited TNF-α production in LPS-induced mouse peritoneal macrophages in vitro via the MAPK pathway

Isofraxidin (IF) is a Coumarin compound that can be isolated from medicinal plants, such as Sarcandra glabra (Thunb.). Nakai is widely used in Asian countries for the treatment of anti-bacterial, anti-inflammatory and anti-tumour action. The present investigation was designed to evaluate the effect of IF on inflammation and nociception. In addition, we investigated a potential novel mechanism to explain the anti-inflammatory properties of IF. In vivo, xylene-induced mouse ear edema, carrageenan-induced rat paw edema, LPS-induced mouse endotoxic shock, acetic acid-induced mice writhing and formalin-induced mouse pain models were used to evaluate the anti-inflammatory activity of IF. In vitro, we examined the effects of IF inhibition on TNF-α production and the regulation of ERK1/2 and p38 phosphorylation activity in LPS-induced mouse peritoneal macrophages. Our results demonstrated that IF can significantly decrease xylene-induced ear edema, carrageenan-induced paw edema, acetic acid-induced writhing and formalin-induced pain. Moreover, IF greatly inhibited the production of TNF-α in the serum of LPS-stimulated mice and peritoneal macrophages, and it decreased phospho-p38 and ERK1/2 protein expression in LPS-stimulated mouse peritoneal macrophages. Overall, our data suggest that IF possesses significant analgesic and anti-inflammatory activities that may be mediated through the regulation of pro-inflammatory cytokines, TNF-α and the phosphorylation of p38 and ERK1/2.     

白细胞介素-10对大鼠佐剂性关节炎的治疗作用

目的　研究白细胞介素 10 (IL 10 )对大鼠佐剂性关节炎 (AA)的治疗作用及免疫机制。方法　测量非致炎侧足肿胀度、体重、脏器系数 ,采用淋巴细胞增殖法和滑膜成纤维细胞 (SFCs)增殖法测定细胞增殖能力和IL 1产生 ,应用酶联免疫吸附测定法 (ELISA)检测IL 4水平。结果　IL 10(每鼠 2 ,10 μg·d-1× 9d ,ip)能缓解AA病情 ,使足肿胀度降低 ,体重、胸腺和脾脏系数及脾细胞增殖能力得到改善 ,腹腔巨噬细胞 (PMΦ)和滑膜组织细胞 (SMCs)产生IL 1水平下降 ,抑制SFCs和引流淋巴结细胞 (LNCs)过度增殖 ,使LNCs和SMCs产生IL 4水平提高。结论　IL 10能用于大鼠AA的治疗 ,其治疗机制与IL 10、IL 4和某些其它细胞因子介导的免疫调节相关     

重组人内抑素对佐剂性关节炎大鼠滑膜细胞增殖及产生细胞因子的影响

目的观察重组人内抑素对体外培养佐剂性关节炎大鼠滑膜细胞的增殖功能及产生细胞因子的影响,探讨其治疗佐剂性关节炎的作用机制。方法采用弗氏完全佐剂(CFA)诱导的佐剂性关节炎(AA)大鼠模型,用足容积法测量关节肿胀度;采用collagenasetypeⅡ消化法分离、培养滑膜细胞,MTT法检测重组人内抑素体内用药对滑膜细胞增殖的影响;放免法检测滑膜细胞上清液中IL-1β、TNF-α的含量。结果CFA致炎后d10,AA大鼠出现继发性炎症,此时皮下注射重组人内抑素(1·25,2·5,5mg·kg-1),连续7d,对照组于d10给予MTX(1·0mg·kg-1)。各剂量组能明显抑制AA大鼠的继发性足肿胀;重组人内抑素体内用药可明显减少AA大鼠滑膜细胞数量,抑制滑膜细胞的增殖,并呈剂量依赖关系;各剂量组均可明显抑制AA大鼠滑膜细胞产生过高的IL-1β和TNF-α。结论重组人内抑素抑制AA大鼠滑膜细胞过度的增殖及过高的细胞因子是其治疗AA的途径之一。