霞水母胶原治疗大鼠佐剂型关节炎的研究

目的 探讨霞水母来源的胶原对大鼠佐剂型关节炎的治疗作用.方法 采用完全弗氏佐剂造成大鼠关节炎模型,致炎后大鼠给予霞水母胶原连续灌胃14 d,观察大鼠双后肢关节肿胀情况,及对血清中一氧化氮(NO),超氧化物歧化酶(SOD)、丙二醛(MDA)的影响.结果 口服霞水母胶原可以降低大鼠的双后肢关节肿胀度,降低大鼠血清中NO和MDA含量,提高大鼠血清中SOD活性.结论 霞水母胶原对佐剂型关节炎有较好的治疗作用,其机理可能与降低体内氧自由基水平及过氧化脂质水平有关.     

可溶性鸡Ⅱ型胶原对关节炎大鼠的免疫治疗作用

目的 :考察口服小剂量可溶性鸡Ⅱ型胶原(SCCⅡ )对大鼠佐剂性关节炎 (AA)的免疫治疗作用。方法 :检测脾细胞、肠系膜淋巴结细胞 (MLNCs)和肠派伊尔结细胞 (PPCs)的ConA增殖反应、腹腔巨噬细胞 (PMΦ)和滑膜细胞 (SMCs)产生IL 1和TNFα水平 ,结合观察踝关节继发炎症、胸腺指数等指标变化。结果 :SCCⅡ (0 .0 3、0 .30和 3.0 0mg·kg- 1·d- 1,ig)治疗 (d 1 2～1 8) ,能提升患鼠脾细胞低下的ConA增殖反应 ,进一步抑制MLNCs和PPCs低下的ConA增殖反应 ,显著抑制PMΦ和SMCs产生IL 1和TNFα,明显减轻大鼠AA的炎症反应。结论 :口服小剂量可溶性SCCⅡ对大鼠AA有免疫治疗作用     

Experimental myocardial infarction in adjuvant arthritis rats

We studied the influence of various inflammatory reactions on the survival rate and occurrence of arrhythmias in the acute phase of experimental myocardial infarction in conscious male Sprague--Dawley CFY rats. Chronic disseminated inflammatory disease was induced by subplantar injection of Freund complete adjuvant, while chronic local inflammatory lesion was produced by carrageenan granuloma pouch method. An acute inflammatory response in the rat paw was evoked by carrageenan. Myocardial infarction was provoked by tightening a previously implanted silk loop around the left anterior descending coronary artery 14 days after the induction of adjuvant disease, and 7 days or 4 h after the production of granuloma pouch or foot edema. Carrageenan paw swelling was induced in rats showing expressed primary and slight secondary lesions due to Freund adjuvant. Adjuvant arthritis, but not granuloma pouch or acute paw edema, protected the rat against the fatal complications of coronary ligation. This effect was characterized by a significant increase in the survival rate from 30% to 63%, and a reduction in the occurrence of various types of dysrhythmias. Carrageenan paw edema was also less expressed and of shorter duration in rats with adjuvant disease. The level of cardiolopin was considerably increased in the arthritic group, while the other phospholipids showed no change. We conclude that chronic disseminated inflammation markedly alters the reactivity of conscious rats to experimental myocardial infarction. The alterations observed may be related to an increased energy supply and/or to accumulation of some endogenous antiinflammatory substances during adjuvant arthritis.     

褪黑素在正常大鼠和佐剂性关节炎大鼠体内的药动学

目的:建立测定大鼠血浆中褪黑素(melatonin,MT)含量的高效液相色谱法(荧光检测),比较正常大鼠及佐剂性关节炎(adjuvant arthritis,AA)模型大鼠灌胃给予MT的药动学特点。方法:分别测定正常大鼠和AA模型大鼠组在不同时间点的血药浓度,将血药浓度-时间(C-t)数据经DAS ver 2.0软件处理,进行药动学参数计算,并对正常大鼠与AA大鼠组进行比较。结果:与正常大鼠组相比,AA模型大鼠10,100μg.kg-1组Cmax,AUC和MRT均显著升高,Tmax,CL/F和Vss/F均显著降低;AA模型大鼠1 000μg.kg-1组Cmax和t1/2显著升高,Tmax,Vss/F,AUC和MRT均显著降低。结论:AA模型大鼠灌胃给予MT 10和100μg.kg-1后,药物吸收速度、吸收总量显著提高,平均滞留时间显著延长。AA模型大鼠灌胃给予MT1 000μg.kg-1后,药物吸收总量下降,平均滞留时间缩短。     

Suppression of adjuvant arthritis in rats by cholesterol

Dietary cholesterol suppressed adjuvant arthritis, a chronic inflammatory disease, in rats, but did not significantly affect carrageenin edema, an acute inflammation. When rats were fed a high-cholesterol diet beginning 10 days before injection of adjuvant, the development of the adjuvant-induced arthritis was greatly suppressed. Cholesterol feeding prevented hypertrophy of the adrenal gland in arthritic rats, but had little influence on the serum corticosterone level. A significant positive correlation was observed between the adrenal weight and the severity of the arthritis. These findings suggest that the effect of cholesterol feeding is not due to increased adrenal sterol synthesis. Dietary cholesterol also prevented hypertrophy of the spleen, but had no effect on atrophy of the thymus in adjuvant-treated rats. Cholesterol-fed rats showed a significant decrease in the serum lipid peroxide level and a significant increase in the serum copper level. Adjuvant treatment not only enhanced hypercholesterolemia produced by cholesterol feeding, but also the level of free cholesterol in serum. These results suggest that dietary cholesterol may exert some effect on the immune response through changes in spleen and liver functions.     

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。     

通痹胶囊对佐剂关节炎大鼠的继发关节病变及免疫功能的影响

目的初步探讨复方中药通痹胶囊对类风湿关节炎(RA)的治疗作用及机制。方法取Wistar雄性大鼠,制成佐剂关节炎(AA)模型,设正常组、模型组、雷公藤多甙对照组、通痹胶囊治疗组,观察不同处理因素对各组实验鼠继发关节肿胀度,继发病变分级,胸腺、脾脏重量及白细胞介素(IL)-1β的影响。结果治疗后通痹胶囊组、雷公藤组的继发关节肿胀,继发病变分级以及对实验鼠的胸腺、脾脏重量、IL-1β的影响与模型组相比差异均有显著性(P<0.05);通痹胶囊组与雷公藤组相比差异无显著性(P<0.05)。结论通痹胶囊对佐剂关节炎大鼠继发病变有明显的治疗作用;对模型大鼠胸腺、脾脏重量及IL-1β的抑制说明该方有一定的免疫抑制作用,这可能是该方治疗RA的机制之一。     

Adjuvant polyarthritis. VIII. Differences in immunopathogenesis between type II collagen arthritis and adjuvant arthritis

The severity of type II collagen-induced arthritis was found to correlate with the serum titers of anti-type II collagen antibody, but not with cell-mediated immunity to type II collagen. In contrast, no significant levels of either the humoral or the cell-mediated immunity to type II collagen were found in rats with Freund's complete adjuvant-induced arthritis. Pre-treatment of young rats with an oily preparation of type II collagen prevented the development of arthritis in these animals in response to a subsequent injection of oily preparation of type II collagen, but had no effect on the development of arthritis in response to a subsequent injection of Freund's complete adjuvant. It is concluded that while an immune response directed toward the injected type II collagen is responsible for the development of type II collagen arthritis, it does not play an important role in the induction of Freund's adjuvant-induced arthritis.     

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。     

尼美舒利对佐剂性关节炎大鼠的治疗作用研究

尼美舒利(Nime)0．6、30、15mg·kg^-1对佐剂性关节炎大鼠的原发性和继发性炎症反应均有明显的抑制作用，用药组继发性炎痘反应的全身症状也明显减轻，而Nime对佐剂性关节炎大鼠低下的脾细胞增殖反应和腹腔巨噬细胞产生过高的IL-1活性却无明显影响，提示Nime无明显的免疫作用，该结果表明，Nime对佐剂性关节炎大鼠有明显的治疗作用，这一作用可能与Nime有较强的抗炎作甩有关。     

青藤碱凝胶对大鼠佐剂性关节炎的治疗作用

目的 :研究青藤碱凝胶 (sinomeninegels,SING)对大鼠佐剂性关节炎 (adjuvantarthritis,AA)的治疗作用。 方法 :用Freund’s完全佐剂诱导大鼠佐剂性关节炎 ,经皮给药 ,观察青藤碱凝胶对大鼠双侧后足跖肿胀度、免疫器官重量及血液流变学的影响。结果 :SING高剂量 (80mg·kg-1)明显抑制AA大鼠双侧后足跖肿胀 ,改善血液流变学 ,但对免疫器官重量无明显影响。SING低剂量 (40mg·kg-1)亦可明显抑制AA大鼠双侧后足跖肿胀度 ,但对血液流变学及免疫器官重量无明显影响。结论 :SING外用对大鼠AA有显著的治疗作用。     

Chemotherapy of arthritis induced in rats by mycobacterial adjuvant

Arthritis induced in rats by mycobacterial adjuvant has been used for the study of compounds of known value in the treatment of rheumatoid arthritis in man. The development of the arthritic syndrome in treated and control rats was followed by measuring the changes in foot thickness of both hind-feet with a micrometer. This method allowed the effect of anti-inflammatory compounds to be expressed quantitatively. Anti-inflammatory activity was readily observed in certain steroids, pyrazolidines, salicylates and sodium aurothiomalate. Chloroquine and hydroxychloroquine were inactive. The inhibition obtained by daily treatment with the steroid paramethasone disappeared when treatment was withdrawn.     

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.     

Decreased hepatobiliary transport of methotrexate in adjuvant arthritis rats

1. We investigated the difference in hepatobiliary transport of methotrexate in normal and adjuvant arthritis (AA) rats and substantiated the expression level of multidrug resistance-associated protein 2 (MRP2) in the liver. 2. Biliary clearance of methotrexate in normal and AA rats was calculated from plasma concentrations and biliary excretion following intravenous infusion and hepatic uptake clearance was estimated from an integration plot using methotrexate concentrations in plasma and liver. 3. Biliary clearance of methotrexate in AA rats was 2.30 ± 0.23 ml?min -1 kg -1 (mean SD) and significantly lower than in normal rats (8.42 ± 0.81 ml?min -1 kg -1) . The uptake clearance of methotrexate in AA rats was also lower than in normal rats (0.138 versus 0.278 ml?min -1 g liver -1) . 4. MRP2 in the liver was detected by fluorescein isothiocyanate-labelled antibody and visualized using a confocal laser microscope system. The expression level of MRP2 in AA rats was very low compared with normal rats, indicating a down-regulation in AA rats. 5. In conclusion, biliary clearance of methotrexate was decreased due to the lower activities in both uptake and canalicular secretion, suggesting that several active transporters in the liver, including MRP2, are down-regulated in AA rats.     

Decreased hepatobiliary transport of methotrexate in adjuvant arthritis rats

1. We investigated the difference in hepatobiliary transport of methotrexate in normal and adjuvant arthritis (AA) rats and substantiated the expression level of multidrug resistance-associated protein 2 (MRP2) in the liver. 2. Biliary clearance of methotrexate in normal and AA rats was calculated from plasma concentrations and biliary excretion following intravenous infusion and hepatic uptake clearance was estimated from an integration plot using methotrexate concentrations in plasma and liver. 3. Biliary clearance of methotrexate in AA rats was 2.30 +/- 0.23 ml min(-1) kg(-1) (mean SD) and significantly lower than in normal rats (8.42 +/- 0.81 ml min(-1) kg(-1)). The uptake clearance of methotrexate in AA rats was also lower than in normal rats (0.138 versus 0.278 ml min(-1) g liver(-1)). 4. MRP2 in the liver was detected by fluorescein isothiocyanate-labelled antibody and visualized using a confocal laser microscope system. The expression level of MRP2 in AA rats was very low compared with normal rats, indicating a down-regulation in AA rats. 5. In conclusion, biliary clearance of methotrexate was decreased due to the lower activities in both uptake and canalicular secretion, suggesting that several active transporters in the liver, including MRP2, are down-regulated in AA rats.     

南蛇藤复方制剂治疗大鼠佐剂性关节炎的研究

目的研究南蛇藤复方制剂对大鼠佐剂性关节炎的影响,探讨其作用机制。方法大鼠予注射弗氏完全佐剂造模,测量大鼠后足肿胀程度,HE染色观察关节病理学改变,ELISA法检测血清MMP-2、MMP-3、TNF-α蛋白含量。结果南蛇藤复方制剂可明显抑制关节肿胀,改善关节的病理学病变,减少大鼠血清中的MMP-2、MMP－3、TNF－α蛋白含量。结论南蛇藤复方制剂治疗大鼠佐剂性关节炎有较好的效果,可能是通过降低血清MMP－2、MMP-3、TNF－α蛋白含量从而减轻或延缓关节损伤。     

Reduced erythrocyte deformability in anemic rats with adjuvant arthritis

Erythrocytes in anemic rats with adjuvant arthritis (AA) were less deformable compared with normal rats. Swelling of the spleen was noticed in anemic rats with AA. The treatment of anemic rats with recombinant human erythropoietin (r-HuEPO; 30 and 100 U/kg, i.v., for 5 days) resulted in a normalization of both the anemia and erythrocyte deformability. It is suggested that erythrocytes with reduced deformability may be sequestered by endothelial slits of the spleen, which may play a causative role in the anemia in rats with AA.     

Suppression of adjuvant arthritis by hesperidin in rats and its mechanisms

The citrus flavonoid hesperidin has been reported to possess a wide range of pharmacological properties. We have investigated the preventive and therapeutic effects of hesperidin on the development of adjuvant arthritis (AA), a rat model of rheumatoid arthritis (RA). Freund's complete adjuvant was used to induce AA in rats. Secondary paw swelling, polyarthritis index and histopathological assessment of ankle joints were used to evaluate the effects of hesperidin on AA rats. Concanavalin-A-induced T-lymphocyte proliferation and interleukin (IL)-2 production by splenocytes were measured using the MTT assay. Levels of IL-1, IL-6 and tumour necrosis factor (TNF)-alpha secreted by peritoneal macrophages (PM) were measured by RIA. Intragastric administration of hesperidin significantly attenuated secondary paw swelling and reduced the polyarthritis index of AA rats in a dose-dependent manner. In addition, hesperidin clearly ameliorated the pathological changes in AA rats. Hesperidin also restored the suppression of T-lymphocyte proliferation and IL-2 production, and downregulated production of IL-1, IL-6 and TNF-alpha by PM in AA rats. Our results suggest that hesperidin improves AA by downregulating the function of over-active macrophages and by up-regulating the activities of dysfunctional T lymphocytes. Hesperidin may therefore have therapeutic value for the clinical treatment of RA. Further research is required to clarify the detailed mechanisms of the protective effects of hesperidin on AA.     

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.