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1.
观察牛磺鹅去氧胆酸 (taurochenodeoxycholic acid,TCDCA)对大鼠佐剂性关节炎(adjuvant arthritis,AA)模型成纤维样滑膜(fibroblast-like synoviocytes,FLS)细胞脂皮素-1(lipocortin 1,LC-1)基因表达的影响,并探讨TCDCA对AA大鼠FLS的作用机制。 制备AA大鼠模型,采用组织块培养法分离培养AA大鼠FLS,应用荧光定量RT-PCR技术检测TCDCA对AA大鼠FLS细胞LC-1 mRNA表达的影响。与模型组相比,TCDCA作用组AA大鼠FLS细胞LC-1 mRNA的表达显著高于模型组(P<0.05)。说明TCDCA能显著促进AA大鼠FLS细胞LC-1 mRNA的表达。  相似文献   

2.
为了进一步探讨牛磺鹅去氧胆酸(TCDCA)对佐剂性关节炎(adjuvant arthritis,AA)模型大鼠治疗作用的分子机制,以AA模型大鼠成纤维样滑膜细胞(fibroblast-like synoviocytes,FLS)为研究对象,采用酶联免疫吸附技术(enzyme linked immune sorbent assay,ELISA)检测了TCDCA对AA模型大鼠FLS中三磷酸肌醇(inositol trisphosphate,IP3)含量的影响。研究结果显示,与空白对照组相比较,TCDCA作用15 min和60 min时AA模型大鼠FLS中IP3的含量显著升高(P0.05),而当TCDCA作用30 min时AA模型大鼠FLS中IP3的含量极显著升高(P0.01)。由此可知,TCDCA能够提高AA模型大鼠FLS中IP3的含量。  相似文献   

3.
《中国兽医学报》2015,(11):1830-1834
为探讨TCDCA对佐剂性关节炎(AA)模型大鼠成纤维样滑膜细胞(FLS)EP2受体mRNA表达的影响,采用Elisa法测定AA模型大鼠FLS内cAMP的含量,以确定TCDCA作用于FLS的最佳药物浓度;采用RT-PCR法测定最佳TCDCA药物浓度对FLS中EP2受体mRNA的表达量。结果表明,PGE2刺激FLS后,FLS内cAMP的浓度和EP2受体mRNA的表达量均显著升高(P0.05),而TCDCA(10-4~10-7 mol/L)能够显著降低PGE2(10-6mol/L)刺激的FLS内cAMP浓度(P0.05),且存在剂量依赖性;TCDCA(10-5~10-7 mol/L)还能够显著降低EP2受体mRNA的表达量(P0.05)。这表明TCDCA对PGE2-EP受体-cAMP信号通路产生影响,是其发挥抗关节炎作用的重要分子机制之一。  相似文献   

4.
[目的]进一步探讨牛磺鹅去氧胆酸(taurochenodeoxycholic acid,TCDCA)在抗炎免疫方面的潜在调节作用。[方法]以AA大鼠成纤维样滑膜细胞作为研究对象,采用ELISA方法检测TCDCA和IL-1β作用下AA大鼠成纤维样滑膜细胞上清液中PGE_2的含量,分析TCDCA对IL-1β刺激下AA大鼠成纤维样滑膜细胞中PGE_2分泌情况的影响。[结果]TCDCA能够对IL-1β刺激下AA大鼠纤维样滑膜细胞PGE_2的分泌产生下调作用(P0.05)。[结论]TCDCA对IL-1β刺激下AA大鼠成纤维样滑膜细胞中PGE_2的分泌具有抑制作用,为TCDCA在兽医临床应用提供依据。  相似文献   

5.
[目的]研究DNA甲基转移酶1(DNMT1)对类风湿性关节炎(RA)模型大鼠关节滑膜成纤维样滑膜细胞(FLS)凋亡的影响。[方法]采用Real-time qPCR检测对照大鼠和RA模型大鼠FLS中DNMT1表达,检测DNMT1 siRNA转染对抗凋亡基因Bcl-2表达的影响;采用MTT检测DNMT1 siRNA转染对FLS增殖的影响。[结果]与对照组相比,RA模型大鼠FLS中DNMT1表达显著升高,DNMT1表达抑制后,Bcl-2表达显著降低;MTT检测发现,DNMT1表达抑制后,FLS增殖活力显著减弱。[结论]DNMT1表达抑制可能引发RA模型大鼠FLS凋亡。  相似文献   

6.
[目的] 进一步探讨牛磺鹅去氧胆酸(taurochenodeoxycholic acid,TCDCA)在抗炎免疫方面的潜在调节作用。[方法] 以AA大鼠成纤维样滑膜细胞作为研究对象,采用ELISA方法检测TCDCA和IL-1β作用下AA大鼠成纤维样滑膜细胞上清液中PGE2的含量,分析TCDCA对IL-1β刺激下AA大鼠成纤维样滑膜细胞中PGE2分泌情况的影响。[结果] TCDCA能够对IL-1β刺激下AA大鼠纤维样滑膜细胞PGE2的分泌产生下调作用(P<0.05)。[结论] TCDCA对IL-1β刺激下AA大鼠成纤维样滑膜细胞中PGE2的分泌具有抑制作用,为TCDCA在兽医临床应用提供依据。  相似文献   

7.
《中国兽医学报》2017,(6):1144-1148
为了研究牛磺鹅去氧胆酸(taurochenodeoxycholic acid,TCDCA)对佐剂性关节炎模型大鼠成纤维样滑膜细胞(fibroblast-like synoviocytes,FLS)中细胞间黏附分子-1(intercellular cell adhesion molecule-1,ICAM-1)表达的影响,采用qPCR与ELISA法检测了FLS中ICAM-1的表达量,结果表明,1×10~(-6)~1×10~(-4) mol/L TCDCA在基因与蛋白水平均能够显著或极显著抑制IL-1β刺激下FLS中ICAM-1的表达(P<0.05或P<0.01),且该抑制作用可被糖皮质激素受体(glucocorticoid receptor,GR)阻断剂米非司酮(RU486)拮抗,提示TCDCA对佐剂性关节炎的治疗作用与抑制GR活性进而抑制ICAM-1表达有关。  相似文献   

8.
采用弗氏完全佐剂建立大鼠佐剂性关节炎(AA)模型,研究黄芪总黄酮(TFA)对AA大鼠关节组织病理损伤的保护作用。取36只大鼠随机分为6组,即空白组,模型组,阳性组,黄芪总黄酮高、中、低剂量组,除空白组外,其余各组大鼠右后足趾皮内注射含弗氏完全佐剂的卡介苗(10mg/mL)0.1mL,建立AA模型。次日,各组灌胃相应药物,连续28d,同时测定大鼠足趾肿胀度和关节炎指数;第29天将大鼠处死,HE染色观察大鼠踝关节滑膜组织及软骨组织的病理组织学变化;免疫组化法观察大鼠滑膜和软骨细胞NF-κB p65的表达。结果表明,TFA能明显降低大鼠原发性足趾肿胀度及多发性关节炎指数;TFA能减轻AA大鼠踝关节炎性细胞浸润及滑膜增生,减少血管翳生成;TFA能抑制NF-κB p65的高表达。说明TFA对AA大鼠的病理损伤有潜在的保护作用。  相似文献   

9.
探讨牛磺鹅去氧胆酸(TCDCA)对糖皮质激素受体(GR)的激活效应,采用免疫荧光术检测NR8383细胞内GR的表达及不同浓度TCDCA对NR8383细胞核移位的影响,采用实时荧光定量PCR法分析了TCDCA对AA大鼠FLS细胞中由GR产生的VCAM-1和COX-2mRNA表达的影响,采用酶联免疫吸附法(ELISA)分析了TCDCA对AA大鼠FLS细胞中由GR介导的VCAM-1蛋白表达的影响。结果表明,TCDCA可以极显著性(P<0.01)的激活NR8383细胞内的GR受体,且在加入GR的特异性抑制剂RU486之后,GR受体的荧光值显著下降,表明RU486阻断了TCDCA对GR受体的激活作用。而TCDCA组和DEX组间无显著性差异(P>0.05);TCDCA可以抑制VCAM-1及COX-2的表达量。由此进一步证明TCDCA是通过GR受体发挥抗炎和免疫调节作用。  相似文献   

10.
采用实时荧光定量PCR法分析了牛磺鹅去氧胆酸(taurochenodeoxycholic acid,TCDCA)对佐剂性关节炎模型(adjuvant arthritis,AA)大鼠成纤维滑膜细胞(fibroblast-like synoviocytes,FLS)中由糖皮质激素受体(glucocorticoid receptor,GR)介导的热休克蛋白90基因(heat shock protein 90 gene,HSP90)mRNA表达的影响。结果表明,TCDCA可以极显著性(P〈0.01)下调FLS细胞内HSP 90 mRNA的表达,同时加入GR的特异性抑制剂RU486后可抑制TCDCA对HSP 90 mRNA的作用。由此证明了TCDCA是通过GR受体发挥抗炎和免疫调节作用的。  相似文献   

11.
牛磺鹅去氧胆酸的抗炎作用机理   总被引:2,自引:0,他引:2  
运用大鼠佐剂性关节炎(AA)模型,牛磺鹅去氧胆酸(TCDCA)按0.2g/kg剂量,经灌胃给药后,测量致炎前和致炎后不同时期大鼠足跖肿胀度,并采用荧光分光光度法和ELISA双抗夹心法分别测定AA大鼠外周血中NO、LTB4含量。结果:TCDCA连续给药21d,可显著抑制AA大鼠不同时期的足跖肿胀,显著降低血清中NO水平;TCDCA连续给药4d,可显著降低AA大鼠外周血中LTB4含量。结论:TCDCA的抗炎作用与其抑制LTB4和NO产生有关。  相似文献   

12.
Lactoferrin (LF) is a ubiquitous protein which exists in milk, plasma, synovial fluids, cerebrospinal fluid and other biological fluids. LF is also well known as a natural immunomodulator. Recently, we found that bovine milk-derived LF (BLF) produced micro-opioid receptor-mediated analgesia. In this study, we examined whether oral administration of BLF causes anti-nociceptive and anti-inflammatory effects, and also whether it modulates LPS-induced TNF-alpha and IL-10 production in rat model of rheumatoid arthritis (RA), rat adjuvant arthritis. BLF was administrated once daily, starting 3 hr before (preventive experiment) or 19 days after (therapeutic experiment) adjuvant injection. In both experiments, BLF suppressed the development of arthritis and the hyperalgesia in the adjuvant-injected paw. The single-administered BLF produced a dose-dependent analgesia, which was reversed by naloxone, in the adjuvant arthritis rats. Both repeated and single administration of BLF suppressed TNF-alpha production and increased IL-10 production in the LPS-stimulated adjuvant arthritis rats. These results suggest that orally administered BLF has both preventive and therapeutic effects on the development of adjuvant-induced inflammation and pain. Moreover, the immunomodulatory properties of BLF, such as down-regulation of TNF-alpha and up-regulation of IL-10, could be beneficial in the treatment of RA. Thus, we concluded that LF can be safely used as a natural drug for RA patients suffering from joint pain.  相似文献   

13.
本试验旨在培养小鼠肾小管上皮细胞(renal tubular epithelial cells,RTECs),探讨马兜铃酸Ⅰ(aristolochic acid Ⅰ,AAⅠ)诱导小鼠肾小管上皮细胞的凋亡情况。AAⅠ与RTECs反应后,从细胞形态学、DNA Ladder、流式细胞仪3个方面检测AAⅠ诱导RTECs的凋亡情况。AAⅠ作用后,随着浓度的增高,上皮细胞失去上皮细胞表型,在20~80 μg/mL作用24 h后,细胞都出现晚期凋亡的特征;在20 μg/mL AAⅠ的作用下早期凋亡的比率随作用时间的延长而增高。AAⅠ可诱导小鼠原代RTECs产生凋亡,凋亡随着作用时间的延长和药物浓度的增大而加剧。  相似文献   

14.
Dysregulation of immune responses within joints plays an important role in development of inflammatory arthritis. We determined expression of a panel of immune response and matrix turnover genes in synovial fluid collected from a group of dogs with stifle oligoarthritis and associated degenerative cranial cruciate ligament (CCL) rupture (n=27). We also studied synovial fluid gene expression in dogs affected with other forms of degenerative arthritis (n=9) and in the stifle joint of healthy dogs with intact CCL (n=14). After collection, synovial cells were pelleted and RNA was isolated. Relative expression of cathepsin K, cathepsin S, tartrate-resistant acid phosphatase (TRAP), matrix metalloproteinase-9 (MMP-9), invariant chain (li), toll-like receptor-2 (TLR-2), and TLR-9 was determined using real-time quantitative RT-PCR. Data were normalized to peripheral blood mononuclear cells (PBMC) as an internal control. Relative expression of cathepsin K, MMP-9, TRAP, and li was increased in the stifle synovial fluid of dogs with oligoarthritis, when compared with the stifles of healthy dogs (P<0.05). In contrast, relative expression of all of the genes-of-interest in synovial fluid from joints affected with other forms of arthritis was not significantly different from the stifles of healthy dogs. TRAP expression was also significantly increased in the stifle joints of dogs with oligoarthritis, when compared to joint expression of TRAP in dogs with other forms of degenerative arthritis (P<0.05). In the dogs with stifle oligoarthritis, expression of both matrix turnover and immune response genes was increased in stifle synovial fluid, when compared with the internal PBMC control, whereas in healthy dogs and dogs with other forms of arthritis, only expression of matrix turnover genes was increased in synovial fluid, when compared with the internal PBMC control (P<0.05). Taken together, these findings suggest that antigen-specific immune responses within the stifle joint may be involved in the pathogenesis of persistent synovitis and associated joint degradation in dogs with oligoarthritis and degenerative CCL rupture.  相似文献   

15.
Arthritis characterized by lameness. Joint swelling and purulent synovial fluid was seen in a group of dairy replacement heifers. Mycoplasma was cultured from one joint aspirate, but all bacterial cultures were negative. Antiglobulins were demonstrated by double diffusion precipitin tests in the serum and synovial fluid. Due to the clinical and clinical pathological similarities to rheumatoid arthritis in man, the disease was called rheumatoid-like arthritis. The presence of antiglobulin may indicate antibody in the synovial fluid explaining the difficulty in culturing a causative agent.  相似文献   

16.
A retrospective evaluation of 64 cases of suspected infectious arthritis in horses was undertaken to determine the relations among histopathologic findings in synovial membrane specimens, cytologic findings in synovial fluid samples, and bacterial culture results. Positive cultures were obtained from 55% of the joints, and 18 different bacterial organisms were cultured. Culturing of synovial fluid yielded bacterial growth more often than did culturing of synovial membrane. Histologic evaluation (H&E and Gram stain) of synovial membrane specimens provided little information to help distinguish infected from culture-negative joints. We do not advocate the routine use of closed synovial biopsy in suspected cases of equine septic arthritis.  相似文献   

17.
Synovial fluid samples of horses with osteoarthritis were investigated to detect interleukin-1 (IL-1) activity which could contribute to the disease pathogenesis. Of the 32 samples tested, 12 (37.5 per cent) showed an augmented phytohaemagglutinin induced proliferation of C3H/HeJ mouse thymocytes. Positive results were also seen in horses with infected arthritis, osteochondritis, traumatic arthritis and undefined synovial effusions. Normal synovial fluid and sera from all groups failed to show any detectable IL-1 activity. Fractionation of synovial fluid showed that the IL-1 activity was in the 15 to 20 Kd fractions. In the absence of mitogen, synovial fluid failed to stimulate thymocytes and did not stimulate the growth of an interleukin-2 (IL-2) dependent CTLL cell line, but synovial fluid stimulated IL-2 release by mouse spleen cells incubated with suboptimal doses of lectin. Evidence of an IL-1 inhibitor in synovial fluid from osteoarthritic horses was provided by ultrafiltration experiments and by the inhibitory activity of synovial fluid at particular dilutions in the thymocyte assay. The presence of IL-1-like activity could be relevant in the pathogenesis of arthritis in horses.  相似文献   

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