白芍总苷对胶原性关节炎大鼠滑膜细胞的作用及机制

目的研究白芍总苷(TGP)对胶原性关节炎(CIA)大鼠滑膜细胞的作用及机制。方法采用鸡II型胶原诱导大鼠CIA模型，胶原酶和胰蛋白酶消化法分离培养大鼠滑膜细胞，透射电镜观察滑膜细胞超微结构的变化，MTT法检测滑膜细胞的增殖能力，滑膜细胞培养上清液中IL-1活性的测定采用小鼠胸腺细胞增殖法，TNFα和PGE₂含量的测定采用放射免疫测定法。结果TGP能有效改善CIA大鼠滑膜细胞超微结构的变化，抑制其过度的增殖反应和产生IL-1，TNFα和PGE₂的水平。结论TGP对CIA大鼠功能亢进的滑膜细胞具有明显的抑制作用，其作用机制可能与其抑制滑膜细胞的过度增殖和分泌能力有关。     

银杏内酯B对慢性炎症血管生成的抑制作用

目的研究银杏内酯B对慢性炎症血管生成的作用及部分作用机制。方法比色法测定小鼠慢性肉芽肿气囊模型血管生成指数，组织形态学方法检测气囊病理变化；放射免疫方法测定白介素-1β(IL-1β)含量；L929生物测定法测定肿瘤坏死因子(TNF-α)含量；RT-PCR法检测IL-1β和TNF-α mRNA的表达。结果银杏内酯B可显著抑制模型小鼠的血管指数，与病理观察结果相符；银杏内酯B可显著抑制模型小鼠血清中IL-1和TNF-α的分泌；能显著抑制PMA诱导的U937细胞IL-1β和TNF-α的分泌及其mRNA的表达。结论银杏内酯B能抑制小鼠慢性炎症性血管生成模型的血管生成，能抑制促血管生成细胞因子IL-1β和TNF-α的转录及表达，这可能是其抑制慢性炎症血管生成的机制之一。     

延龄草苷对脂多糖刺激的小胶质细胞炎症抑制作用

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。     

甘草酸苷通过MAPK p38/NF-κB通路对炎症后色素沉着的抑制作用

目的 探讨甘草酸苷对脂多糖（lipopolysaccharide,LPS）刺激后角质形成细胞分泌COX-2/PGE₂和对共培养黑素细胞合成黑素的影响,并探讨其可能的作用机制。方法 以人表皮角质形成细胞为对象,分为对照组、LPS组、甘草酸苷组（2,5,10 μmol·L^-1）。采用ELISA法检测PGE₂的含量,Western blot检测细胞COX-2、NF-κB p-p65、p-IKKα/β和MAPKp-p38蛋白的表达,比色法检测共培养黑素细胞的黑素含量。结果 与对照组比较,LPS显著增加角质形成细胞COX-2、NF-κB p-p65、p-IKKα/β、MAPK p-p38蛋白表达（P<0.01）和PGE₂的分泌（P<0.01）,增加共培养黑素细胞黑素生成（P<0.01）。与LPS组比较,甘草酸苷呈剂量依赖性抑制COX-2、NF-κB p-p65、p-IKKα/β、MAPK p-p38蛋白表达（P<0.05）和PGE₂的分泌（P<0.05）,减少共培养黑素细胞黑素生成（P<0.05）。结论 甘草酸苷通过抑制角质形成细胞MAPK p38/NF-κB通路,从而降低COX-2/PGE₂的表达,减少共培养黑素细胞合成黑素。     

依托泊苷对小鼠变应性接触性皮炎的影响及作用机制探讨

观察依托泊苷(etoposide，VP-16)对小鼠变应性接触性皮炎(allergic contact dermatitis，ACD)的抗炎作用并探讨其可能的机制。采用2,4-二硝基氟苯(dinitrofluorobenzene，DNFB)致小鼠ACD模型，观察VP-16给药后皮肤炎症反应程度，应用放射免疫分析法测定血清中肿瘤坏死因子α(tumor necrosis factor-α，TNF-α)和白细胞介素-10(interleukin-10，IL-10)的水平，免疫组化法测定皮肤中细胞间粘附分子(intercellular adhesion molecule，ICAM-1)的表达。结果显示，VP-16可显著降低炎性细胞浸润，减轻炎症反应程度，明显降低血清中炎症促发因子TNF-α的水平及皮肤中ICAM-1的表达。VP-16可以有效抑制DNFB诱发的小鼠ACD，可能通过对某些细胞因子的抑制而发挥作用。     

雷公藤红素对IL-1和IL-2活性及PGE2释放的抑制作用

雷公藤红素0.1～1.0μg/ml在试管内能降低LPS诱导的小鼠腹腔巨噬细胞外和细胞内白细胞介素-1(IL-1)的活性,也能抑制ConA诱导的小鼠脾细胞产生白细胞介素-2(IL-2).动态观察表明,雷公藤红素经预处理8h和3h后已能分别抑制IL-1和IL-2的产生。此外,雷公藤红素能降低A23187刺激家兔滑膜细胞释放前列腺素E₂(PGE₂)。     

羟基红花黄色素A对脑缺血大鼠皮层炎症信号转导途径相关因子的抑制作用

羟基红花黄色素A(hydroxysafflor yellow A，HSYA)是红花中的单体有效成分。本研究采用线栓法制备大鼠永久性脑缺血模型，观察HSYA对永久性脑缺血大鼠炎症信号转导途径相关因子的抑制作用。于缺血后3、 6、 12和24 h取大脑皮层。Western blotting 检测细胞核及胞浆核转录因子κB(NF-κB) p65及胞浆磷酸化IκB-α(pIκB-α)蛋白水平表达；Trans AM试剂盒检测NF-κB DNA结合活性；RT-PCR检测炎性因子TNF-α、 IL-1β、 IL-6和IL-10转录水平表达。结果表明，大鼠脑缺血后多次静脉注射HSYA(10 mg·kg^-1)，能显著抑制p65核转位以及IκB-α的磷酸化，降低NF-κB DNA结合活性，并降低促炎因子TNF-α、 IL-1β和IL-6 mRNA表达，升高抗炎因子IL-10 mRNA表达水平。提示HSYA的抗脑缺血作用可能与其抑制炎症信号途径中NF-κB激活及炎性因子转录水平表达有关。     

前列腺素E1经不同途径给药后的大鼠体内药效学比较

本文研究了前列腺素E₁(PGE₁)分别经不同途径给药后的大鼠体内药效学，旨在寻找目前PGE₁注射给药的替代途径。以PGE₁降压效应作为药效学指标，以静脉注射为对照，分别测定PGE₁经鼻腔、舌下、肌肉(im)、腹腔(ip)给药后的药效学参数，包括峰效应时间(Tmax)，血压下降最大百分数(Emax，%)，效应持续时间(T_d)以及血压下降百分数-时间曲线下面积(AUC，%·min)。研究结果表明，PGE₁经上述途径给药后，药效学参数Emax，T_d，AUC等均随给药剂量的增加而增大，提示存在明显的剂量-效应关系。根据所测Tmax值，推断上述给药途径其吸收速率的大小顺序为：鼻腔≈im>ip>舌下；依据所测药理生物利用度(PF)值，预测药物绝对生物利用度的顺序为：鼻腔>im≈ip>舌下。上述研究结果提示，PGE₁经鼻腔与舌下黏膜给药，有望替代目前的注射给药。     

罗浮山风湿膏药联合硫酸氨基葡萄糖治疗风寒湿痹型膝骨关节炎临床观察

目的 探讨罗浮山风湿膏药联合硫酸氨基葡萄糖治疗风寒湿痹型膝骨关节炎临床疗效。方法 选择中国中医科学院广安门医院2021年9月—2022年5月收治的膝骨关节炎（风寒湿痹型）患者122例,依照随机数字表法分为对照组、试验组,每组61例,对照组采用硫酸氨基葡萄糖,试验组联合罗浮山风湿膏药治疗,比较两组临床疗效,比较两组治疗前后中医证候积分,病情严重程度［骨关节炎指数（WOMAC）］、膝关节功能［Lysholm膝关节评分表（LKSS）］、生活质量［日常生活活动能力（ADL）］,骨代谢指标［骨钙素（BGP）、骨保护素（OPG）、血清I型胶原交联C末端肽（CTX-I）、CTX-II］,疼痛相关介质［血清P物质（SP）、前列腺素E₂（PGE₂）、5-羟色胺（5-HT）］,炎症因子水平［白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）、C反应蛋白（CRP）］,并统计不良反应发生率。结果 两组的总有效率相比,试验组更高（P＜0.05）。治疗前两组中医证候积分,病情严重程度、骨代谢指标、疼痛相关介质、炎症因子水平比较差异均无统计学意义（P＞0.05）。治疗后,两组患者中医证候各项积分均较本组治疗前显著降低（P＜0.05）,且治疗后试验组显著低于对照组（P＜0.05）。治疗后,两组WOMAC评分均较本组治疗前显著降低（P＜0.05）,两组LKSS、ADL评分均较本组治疗前显著升高（P＜0.05）,且试验组WOMAC评分较对照组低,LKSS、ADL评分较对照组高（P＜0.05）;两组骨代谢指标组间比较差异无统计学意义（P＞0.05）;两组疼痛相关介质SP、PGE₂、5-HT均较本组治疗前显著降低（P＜0.05）,且试验组SP、PGE2、5-HT水平显著低于对照组（P＜0.05）;两组疼痛相关介质SP、PGE₂、5-HT均较本组治疗前显著降低（P＜0.05）,且试验组SP、PGE₂、5-HT水平显著低于对照组（P＜0.05）;两组炎症因子IL-1β、IL-6、TNF-α、CRP水平均较本组治疗前显著降低（P＜0.05）,且试验组IL-1β、IL-6、TNF-α、CRP水平均较对照组低（P＜0.05）;试验组疼痛缓解时间、疼痛消失时间以及关节活动度复常时间均短于对照组（P＜0.05）。两组不良反应发生率无统计学意义（P＞0.05）。结论 罗浮山风湿膏药联合硫酸氨基葡萄糖治疗风寒湿痹型膝骨关节炎患者的效果明显,可减轻病情、改善膝关节功能、提高生活质量,还可减少疼痛介质,减轻炎症反应,且安全性高。     

17β-雌二醇对人的类成骨细胞株TE85和U2功能的调节

目的：以人的类成骨细胞株TE85和U2为细胞模型，观察雌激素对细胞功能的影响。方法：³H-胸腺嘧啶参入法测细胞增殖；ELISA法测细胞因子IL-6含量；精氨酸转化法测iNOS活性。结果：IL-1(20 U.mL^-1)和TNFα(50 U.mL^-1)刺激细胞分泌IL-6，并抑制细胞增殖。在TE85细胞，17β-雌二醇(E₂)可抑制IL-6分泌并能对抗IL-1和TNFα对细胞增殖的影响。NOS抑制剂L-NMMA使细胞³H-胸腺嘧啶的参入降低，E₂(1 nmol.L^-1)可对抗L-NMMA的抑制作用。结论：E₂通过减少IL-6分泌和影响iNOS活性而调节细胞功能。     

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。     

DBA/1小鼠胶原性关节炎模型建立方法及评价指标

目的建立DBA/1小鼠胶原性关节炎(collagen in-duced arthritis,CIA)模型及主要评价指标。方法鸡Ⅱ型胶原(typeⅡ collagen,CⅡ)免疫DBA/1小鼠诱导CIA,进行关节炎指数评分、足爪X线摄片、踝关节和脾脏病理检查及评分。结果免疫后d31,CIA小鼠足爪红肿,关节炎指数评分增高,d40～60为肿胀高峰;d35,体重下降;足爪X线片示关节变形,骨赘生成,骨质溶解;踝关节病理见滑膜组织增生,炎细胞浸润,血管翳出现;脾脏病理见生发中心增多,白髓淋巴样滤泡增生,边缘区细胞密度增大、红髓淤血。踝关节和脾脏病理评分明显高于正常小鼠。结论鸡CⅡ免疫DBA/1小鼠诱导CIA方法可靠,重复性好,CIA发病率高。关节炎指数、足爪X线片、踝关节和脾脏病理等是评价CIA模型的主要指标。     

Human TNF-alpha gene vaccination prevents collagen-induced arthritis in mice

TNFalpha is a key factor in the pathogenesis of rheumatoid arthritis. To investigate whether heterologous TNFalpha gene vaccination could induce anti-TNFalpha antibodies via cross-reaction and prevent the inflammatory arthritis, we constructed two plasmids by inserting a full-length cDNA of human TNFalpha into a secreted vector (pSecTag-TNFalpha) and a non-secreted vector (pTARGE-TNFalpha), respectively. Administering either plasmid to collagen-induced arthritis (CIA) mice reduced paw swelling and synovium-infiltrating inflammatory cells. This reduction was accompanied by down-regulated TNFalpha in sera and joints. The spleen cells from treated CIA mice displayed decreased IFN-gamma mRNA levels and matrix metalloproteinase-9 bioactivity in comparison with those from CIA control. Furthermore, both spontaneous and collagen-specific proliferation of the lymphocytes was significantly decreased after treatment. Administration of plasmids led to an elicited production of antibodies to both human and mouse TNFalpha. These results suggest that human TNFalpha gene vaccination prevents CIA in mice likely by inducing cross-reactive antibodies against TNFalpha, and that heterologous gene vaccination might provide an effective therapeutic strategy to battle TNFalpha mediated diseases.     

Therapeutic effects of glucosides of Cheanomeles speciosa on collagen-induced arthritis in mice

AIM: To investigate the therapeutic effect of the glucosides of Cheanomeles speciosa (GCS) on the collagen-induced arthritis (CIA) in mice. METHODS: Mice were divided randomly into six groups, including normal, CIA, CIA GCS (60, 120, and 240 mg/kg) and CIA glucosides of Tripterygium wilfordii (GTW) groups. CIA model was based on mice. The effect of GCS in CIA mice was measured by paw-swelling, arthritis scores, and histo-pathological assessment of synovium. Indices of thymus and spleens were measured. Thymocytes and splenocytes proliferation, activity of interleukin-1 (IL-1), and interleukin-2 (IL-2) were assayed by MTT and [3H]TdR method. The level of anti-collagen type Ⅱ (CII) antibody in serum and prostaglandin E (PGE) in ankle were assayed by ELISA and ultraviolet spectrophotometer method, respectively. RESULTS: The onset of paw-swelling was on d 24 after injection of emulsion. The peak of secondary inflammation appeared on d 36 and then declined after d 40. GCS and GTW significantly reduced paw-swe     

Taurine chloramine inhibits osteoclastogenesis and splenic lymphocyte proliferation in mice with collagen-induced arthritis

Taurine chloramine (TauCl) is produced by activated neutrophils in the inflammatory joint cavities of rheumatoid arthritis and is known to have anti-inflammatory and anti-arthritic effects. However, the mechanisms underlying the anti-arthritic effect of TauCl have not been elucidated. Here, we investigated that mechanism using a collagen-induced arthritis (CIA) mouse model. DBA/1J mice were immunized with bovine type II collagen to induce CIA and were given daily subcutaneous injections of TauCl from the day of first collagen immunization. Severity of arthritis was scored by paw swelling and the arthritis score system. At the 8th week, mice were sacrificed for histological examination using hematoxylin and eosin, safranin-O and tartrate-resistant acid phosphatase (TRAP) staining. Effects of TauCl on osteoclastogenesis from bone marrow-derived preosteoclasts and proliferation of the lymphocytes obtained from spleens of CIA mice were determined. TauCl significantly attenuated the severity of paw swelling and reduced arthritis score in CIA mice. TauCl treated CIA mice showed significant reductions of synovial inflammation, cartilage damage and bone erosion. The number of TRAP-positive cells in the joints of TauCl treated CIA mice was reduced. TauCl inhibited osteoclastogenesis from the RANKL treated bone marrow-derived preosteoclasts in a dose-dependent manner. TauCl also inhibited the proliferation of splenic lymphocytes obtained from CIA mice. In conclusion, TauCl attenuated the severity of CIA by inhibiting lymphocyte proliferation and osteoclastogenesis. Combined our results suggest that TauCl produced endogenously in inflamed joints may suppress the development of rheumatoid arthritis and that TauCl may be used for therapeutic treatment of rheumatoid arthritis.     

Celastrol attenuates collagen-induced arthritis via inhibiting oxidative stress in rats

The present work aimed to investigate the anti-rheumatism effect and the mechanism of celastrol in collagen-induced arthritis (CIA) rats. The CIA model was established in male Wistar rats by intradermal injection of bovine collagen-II in complete Freund's adjuvant (CFA) at the base of tail. The rats received oral administration of celastrol for 28 days. A variety of indicators, including paw swelling and arthritis scores, were measured for anti-rheumatism effect. Celastrol treatment attenuated paw swelling and arthritis scores in CIA rats. Celastrol improved the spleen and thymus indexes in CIA rats. The increased levels of inflammatory cytokines, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and interferon (IFN)-γ, were abolished by celastrol treatment. In addition, the weakened superoxide dismutase (SOD) activity, the increased levels of malondialdehyde (MDA), and superoxide anions, and enhanced NADPH oxidase (Nox) activity were all reversed by celastrol treatment. Nox4 overexpression reversed the attenuating effects of celastrol on paw swelling and arthritis scores in CIA rats. The celastrol-induced improvement in spleen and thymus indexes in CIA rats was inhibited by Nox4 overexpression. Nox4 overexpression reversed the abolishing effects of celastrol on the increases of TNF-α, IL-1β, IL-6, and IFN-γ levels in the serum of CIA rats. These results demonstrated that celastrol improved rheumatism in arthritis via inhibiting oxidative stress.     

木瓜苷对小鼠胶原性关节炎的预防作用及初步机制

目的　研究木瓜苷 (GCS)预防用药对小鼠胶原性关节炎 (collagen inducedarthritis,CIA)的影响 ,并探讨其初步机制。方法　昆明种小鼠随机分为 6组 :正常对照组、模型组、木瓜苷三个剂量组和青藤碱组 (SIN) ;鸡Ⅱ型胶原免疫小鼠诱导继发性关节炎 ;足爪容积测定法、关节炎评分法和跖曲踝关节疼痛评分法观察关节炎的发生情况 ;观察胸腺指数、脾脏指数变化 ;3 H TdR参入法检测T、B细胞增殖反应 ;IL 1、IL 2活性的检测采用小鼠淋巴细胞增殖法 ;ELISA法检测血清中抗Ⅱ型胶原抗体水平 ;分光光度法测定局部踝关节PGE水平。结果　小鼠免疫后d 2 4 ,足爪出现红肿 ,继发性炎症高峰期在d 36 ,4 0后炎症逐渐减轻。GCS(6 0、12 0、2 4 0mg·kg-1)和SIN(10 0mg·kg-1)ig对CIA小鼠继发性关节炎有明显的抑制作用 ,降低CIA小鼠踝关节中增高的PGE ;CIA小鼠脾脏指数增加 ,而胸腺指数未见明显的改变 ,GCS能降低增加的CIA小鼠脾脏指数 ,对胸腺指数无明显影响 ;GCS(6 0、12 0、2 4 0mg·kg-1)和SIN (10 0mg·kg-1)使CIA小鼠增高的ConA和LPS诱导的T细胞和B细胞增殖反应降低 ;使T细胞和PMΦ分别产生的高水平IL 2和IL 1降至正常范围 ;并降低CIA小鼠血清中升高的抗CⅡ抗体。结论　GCS和SIN具有明显的抗炎作用 ,此作用可能是通过抑制     

褪黑素对小鼠胶原性关节炎的防治作用

目的　研究褪黑素 (Melatonin ,MT)对小鼠胶原性关节炎 (Collagen inducedarthritis ,CIA)的防治作用。 方法　在建立小鼠CIA模型的基础上 ,检测小鼠足爪炎症的肿胀度和评分 ,分光光度计法检测前列腺素 ,3 H TdR参入法检测脾淋巴细胞增殖反应 ,白细胞介素 1(IL 1)和IL 2 ,HE染色法对关节组织作病理检查。结果　MT (10、10 0、10 0 0 μg·kg-1)ig给药能明显减轻CIA小鼠的关节炎症 ,抑制CIA小鼠过高的ConA增殖反应和小鼠腹腔巨噬细胞IL 1的过度产生 ,降低脾淋巴细胞产生的IL 2的水平 ,降低CIA小鼠踝关节组织中高水平的PGE含量 ,同时病理检查发现预防用药MT可改善局部关节炎症状况 ,抑制CIA小鼠滑膜增生 ,减轻炎性细胞浸润。结论　MT对CIA具有防治作用 ,其机制与其调节免疫功能有关     

Effects and mechanisms of glucosides of chaenomeles speciosa on collagen-induced arthritis in rats

Effects of glucosides of chaenomeles speciosa (GCS)-a Chinese traditional herbal medicine (CTM) on inflammatory and immune responses and its mechanisms in collagen-induced arthritis (CIA) rat were studied. Hind paw volumes of rats were measured by volume meter; lymphocyte proliferation, interleukin-1, interleukin-2, TNF-alpha level was determined by 3-(4,5-2 dimethylthiazal-2yl)2,5-diphenyltetrazoliumbromide (MTT) assay; cAMP level in synoviocytes was analyzed by competitive protein binding assay (CPBA). mRNA expression of G(i,), G(s), and TNF-alpha of synoviocytes in CIA rats was measured by RT-PCR and antibodies to collagen type II (CII) were determined by enzyme-linked immunosorbent assay (ELISA), respectively. There was a marked secondary inflammatory response in CIA model, which accompanied with the decrease of body weight and the weight of immune organs simultaneously. The administration of GCS (30, 60, 120 mg x kg(-1), ig x 7 days) inhibited the inflammatory response and restored body weight and the weight of immune organs of CIA rats. Lymphocyte proliferation and IL-2 production of CIA rats increases, together with IL-1 and TNF-alpha in peritoneal macrophages and synoviocytes. The administration of GCS (30, 60, 120 mg x kg(-1), ig x 7 days) reduced above changes significantly. GCS at the concentration of 0.5, 2.5, 12.5, 62.5, 125 mg x l(-1) increased cAMP level of synoviocytes, which decreased in CIA rats in vitro. At the same time, GCS inhibited mRNA expression of G(i,) and TNF-alpha of synoviocytes and increased mRNA expression of G(s) of synoviocytes in CIA rats. GCS had no effect on the concentration of antibodies to CII. GCS possesses anti-inflammatory and immunoregulatory actions and has a therapeutic effect on CIA rats due to G protein-AC-cAMP transmembrane signal transduction of synoviocytes, which play a crucial role in pathogenesis of this disease.