白花蛇舌草对Ⅱ型胶原蛋白诱导的大鼠类风湿性关节炎的治疗作用
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摘要
目的:探讨白花蛇舌草(HD)对Ⅱ型胶原蛋白诱导的大鼠类风湿性关节炎(CIA)的治疗作用。方法:取SD大鼠60只随机分为对照组10只、造模组50只,造模组于背部皮内注射II型胶原乳剂建立CIA大鼠模型,采用大鼠关节炎评分法评价其模型是否复制成功。造模组再随机分为模型组、雷公藤多苷(GTW) 6 mg/kg组、白花蛇舌草3、6、12 g/kg组,每组10只,每天灌胃给予相应的试剂。每周观察关节炎指数和痛阈,于连续干预28 d后,各组大鼠眼眶静脉取血,观察白细胞介素1β(IL-lβ)、肿瘤坏死因子-α(TNF-α)、前列腺素E2(PGE2)、核因子κB受体活化因子配体(RANKL)及护骨素(OPG)水平。结果:与对照组比较,模型组大鼠关节炎指数,血清IL-lβ、TNF-α、PGE2、RANKL、OPG及RANKL/OPG水平均明显升高(P<0.05),光照阈值明显降低(P<0.05);与模型组比较,雷公藤多苷组、白花蛇舌草低、中、高剂量组关节炎指数,血清IL-lβ、TNF-α、PGE_2、RANKL、OPG及RANKL/OPG水平均明显降低(P<0.05),光照阈值明显升高(P<0.05)。结论:白花蛇舌草可明显降低CIA模型大鼠关节炎指数,升高痛域阈值,下调IL-lβ、TNF-α、PGE_2、RANKL、OPG水平,从而有效的防治CIA。
Objective: To investigate the therapeutic effects of Hedyotis diffusa Willd.on type II collagen-induced rheumatoid arthritis in rats.Methods: According to the random number table,60 SD rats were divided into the normal control group( n = 10,normal saline) and model group( n = 50).The collagen-induced arthritis model was established with the injection of type II collagen into the back in rats other than the normal group and evaluated by arthritis score,then the model rats were randomly divided into model group(normal saline),tripterygium wilfordii polyglycoside(GTW) 6 mg/kg group(daily dose: 0.4 mg/kg),HD 3,6,12 g/kg groups(daily dose: 3,6 and 12 g/kg,respectively),with 10 rats in each group. The rats were treated with corresponding agents by intragastric administration.The arthritis index and the pain threshold of all rats at different time points were observed and measured weekly.After treated by intragastric administration for 28 days,all rats were killed to measure the changes of serum cytokine levels including interleukin 1β( IL-lβ),tumor necrosis factor a( TNF-a),prostaglandin( PGE2),receptor activator for nuclear factor-kappa B ligand(RANKL) and osteoprotegerin(OPG).Results: Compared with the control group,the arthritis index and the serum levels of IL-lβ,TNF-a,PGE2,RANKL,OPG and RANKL/OPG of the model group were increased significantly(P<0.05),the pain threshold of the model group was decreased significantly( P<0.05); compared with the model group,the arthritis index and the serum levels of IL-lβ,TNF-a,PGE_2,RANKL,OPG and RANKL/OPG of the GTW group,HD low-dose,medium-dose,high dose groups were decreased significantly( P<0.05),the pain threshold of the model group was increased significantly( P < 0. 05). Conclusion: Hedyotis diffusa Willd.can significantly reduce arthritis index and increase pain threshold,reduce the level of IL-lβ,TNF-a,PGE_2,RANKL,OPG,and RANKL/OPG,then can prevent CIA effectively.
Objective: To investigate the therapeutic effects of Hedyotis diffusa Willd.on type II collagen-induced rheumatoid arthritis in rats.Methods: According to the random number table,60 SD rats were divided into the normal control group( n = 10,normal saline) and model group( n = 50).The collagen-induced arthritis model was established with the injection of type II collagen into the back in rats other than the normal group and evaluated by arthritis score,then the model rats were randomly divided into model group(normal saline),tripterygium wilfordii polyglycoside(GTW) 6 mg/kg group(daily dose: 0.4 mg/kg),HD 3,6,12 g/kg groups(daily dose: 3,6 and 12 g/kg,respectively),with 10 rats in each group. The rats were treated with corresponding agents by intragastric administration.The arthritis index and the pain threshold of all rats at different time points were observed and measured weekly.After treated by intragastric administration for 28 days,all rats were killed to measure the changes of serum cytokine levels including interleukin 1β( IL-lβ),tumor necrosis factor a( TNF-a),prostaglandin( PGE2),receptor activator for nuclear factor-kappa B ligand(RANKL) and osteoprotegerin(OPG).Results: Compared with the control group,the arthritis index and the serum levels of IL-lβ,TNF-a,PGE2,RANKL,OPG and RANKL/OPG of the model group were increased significantly(P<0.05),the pain threshold of the model group was decreased significantly( P<0.05); compared with the model group,the arthritis index and the serum levels of IL-lβ,TNF-a,PGE_2,RANKL,OPG and RANKL/OPG of the GTW group,HD low-dose,medium-dose,high dose groups were decreased significantly( P<0.05),the pain threshold of the model group was increased significantly( P < 0. 05). Conclusion: Hedyotis diffusa Willd.can significantly reduce arthritis index and increase pain threshold,reduce the level of IL-lβ,TNF-a,PGE_2,RANKL,OPG,and RANKL/OPG,then can prevent CIA effectively.
引文
[1] Felcenloben I,Piasecki T,Miller J,et al. Adoptivelytransferred Tregs accumulate in a site-specific mannerand ameliorate signs of less advanced collagen-inducedarthritis progress in rats[J]. Immunotherapy,2015,7(3):215-228.
[2]严国鸿,江川,潘旭东,等.双藤痹痛凝胶膏剂对胶原诱导性关节炎模型大鼠炎性细胞因子表达的影响[J].江西中医药大学学报,2017,29(4):76-78.
[3]刘彩丽,王颖瑛. TNF-α/NF-κB信号通路在依那西普缓解大鼠类风湿性关节炎中的作用[J].中国应用生理学杂志,2017,33(4):373-376.
[4]向艳丽,石思蓉,覃晓莉,等.大豆多肽Lunasin对类风湿关节炎大鼠T细胞免疫指标的影响[J].中国应用生理学杂志,2018,34(1):13-15.
[5] Yamashita T,Hagino H,Nagashima H. Effect of ONO-0980250,a cathepsin K inhibitor,on arthritis,and bonemineral density in rats with collagen induced arthritis[J].Osteoporo Sarcopenia,2015,1(2):138-139.
[6]张丽华,朱梦雅,王丽芳,等.重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白对胶原诱导性关节炎大鼠骨质及骨保护素的影响[J].中国骨质疏松杂志,2013,19(1):6-9.
[7] Shi M,Cui F,Liu AJ,et al. The protective effects ofchronic intermittent hypobaric hypoxia pretreatment a-gainst collagen-induced arthritis in rats[J]. J Inflamm,2015,12:23-24.
[8]刘益杰,冯伟,何东仪,等.淫羊蕾苷对Ⅱ型胶原诱导型关节炎大鼠骨破坏及血清RANKL/OPG的干预作用[J].中国中西医结合杂志,2013,33(9):1221-1225.
[9]樊秋贵,郭钧,杨民. OPG、RANKL、RANK等因子在类风湿性关节炎患者血清及滑膜液中的变化及意义[J].中华风湿病学杂志,2007,11(1):38-40.
[10] Lyu QW,Zhang W,Shi Q,et al. Comparison ofTripterygium wilfordii Hook F with methotrexate in thetreatment of active rheumatoid arthritis(TRIFRA):arandomised,controlled clinical trial[J]. Ann RheumDis,2015,74(6):1078-1086.
[2]严国鸿,江川,潘旭东,等.双藤痹痛凝胶膏剂对胶原诱导性关节炎模型大鼠炎性细胞因子表达的影响[J].江西中医药大学学报,2017,29(4):76-78.
[3]刘彩丽,王颖瑛. TNF-α/NF-κB信号通路在依那西普缓解大鼠类风湿性关节炎中的作用[J].中国应用生理学杂志,2017,33(4):373-376.
[4]向艳丽,石思蓉,覃晓莉,等.大豆多肽Lunasin对类风湿关节炎大鼠T细胞免疫指标的影响[J].中国应用生理学杂志,2018,34(1):13-15.
[5] Yamashita T,Hagino H,Nagashima H. Effect of ONO-0980250,a cathepsin K inhibitor,on arthritis,and bonemineral density in rats with collagen induced arthritis[J].Osteoporo Sarcopenia,2015,1(2):138-139.
[6]张丽华,朱梦雅,王丽芳,等.重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白对胶原诱导性关节炎大鼠骨质及骨保护素的影响[J].中国骨质疏松杂志,2013,19(1):6-9.
[7] Shi M,Cui F,Liu AJ,et al. The protective effects ofchronic intermittent hypobaric hypoxia pretreatment a-gainst collagen-induced arthritis in rats[J]. J Inflamm,2015,12:23-24.
[8]刘益杰,冯伟,何东仪,等.淫羊蕾苷对Ⅱ型胶原诱导型关节炎大鼠骨破坏及血清RANKL/OPG的干预作用[J].中国中西医结合杂志,2013,33(9):1221-1225.
[9]樊秋贵,郭钧,杨民. OPG、RANKL、RANK等因子在类风湿性关节炎患者血清及滑膜液中的变化及意义[J].中华风湿病学杂志,2007,11(1):38-40.
[10] Lyu QW,Zhang W,Shi Q,et al. Comparison ofTripterygium wilfordii Hook F with methotrexate in thetreatment of active rheumatoid arthritis(TRIFRA):arandomised,controlled clinical trial[J]. Ann RheumDis,2015,74(6):1078-1086.