热痹康汤对胶原诱导性关节炎大鼠滑膜血管内皮生长因子的影响
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摘要
目的:观察清热解毒抗风湿方药——热痹康汤对胶原诱导性关节炎(CIA)大鼠滑膜血管内皮生长因子(VEGF)的影响。方法:将60只清洁级雌性Wistar大鼠随机分为空白对照组,模型对照组,甲氨蝶呤组,热痹康汤低、中、高剂量组,每组10只。除空白对照组外,其余各组大鼠采用弗氏不完全佐剂联合牛Ⅱ型胶原蛋白诱导CIA大鼠模型。造模成功后开始给药,模型对照组给予生理盐水灌胃,热痹康汤低、中、高剂量组分别给予热痹康汤提取物低、中、高剂量灌胃,甲氨蝶呤组给予甲氨蝶呤灌胃,空白对照组大鼠自由饮水和进食。观察不同剂量热痹康汤对CIA大鼠的关节肿胀指数及其滑膜VEGF的影响。结果:热痹康汤各剂量组及甲氨蝶呤组大鼠的关节肿胀指数均低于模型对照组(P<0.01),其中中剂量热痹康汤作用与甲氨蝶呤相当(P>0.05),高剂量热痹康汤作用优于甲氨蝶呤(P<0.01);热痹康汤各剂量组及甲氨蝶呤组大鼠滑膜的VEGF水平均低于模型对照组(P<0.05),其中高剂量热痹康汤作用优于甲氨蝶呤(P<0.05),中、低剂量热痹康汤作用与甲氨蝶呤相当(P>0.05)。结论:热痹康汤治疗类风湿关节炎的机制是通过抑制滑膜VEGF的产生而实现的。
Objective:To observe the effect of Rebikang Tang(热痹康汤 —a prescription of clearing away heat and toxic materials and anti-rheumatism)on vascular endothelial growth factor(VEGF)in rats with collagen-induced arthritis(CIA).Methods:Sixty clean-grade female Wistar rats were randomly divided into a blank control group,a model control group,a methotrexate group,and low,medium and high-dose Rebikang Tang groups,10 rats in each group.Except the blank control group,the rats in the other groups were induced by the incomplete adjuvant combined with collagen type Ⅱ to establish CIA rat models.The model control group was given intragastric administration of physiological saline,the low,medium and high-dose Rebikang Tang groups were given corresponding dose of Rebikang Tang,the methotrexate group was given intragastric administration of methotrexate and the rats in the control group could drink water and eat food freely.The effects of different doses of Rebikang on joint swelling index and VEGF were observed.Results:The joint swelling indexes in each dose of Rebikang group and the methotrexate group were lower than that of the model group(P < 0.01),among which the effect in the medium-dose Rebikang group was equivalent to that of the methotrexate group(P > 0.05) and the effect in the high-dose Rebikang group was superior to that of the methotrexate group(P < 0.01).The synovial VEGF levels in each Rebikang group and the methotrexate group were lower than that of the model control group(P < 0.05),among which the effect of the high-dose Rebikang group is superior to the methotrexate(P < 0.05),while the effects of the middle and low-dose Rebikang groups were equivalent to the methotrexate(P > 0.05).Conclusion:The mechanism of Rebikang Tang in the treatment of rheumatoid arthritis can be achieved by inhibiting the generation of VEGF.
Objective:To observe the effect of Rebikang Tang(热痹康汤 —a prescription of clearing away heat and toxic materials and anti-rheumatism)on vascular endothelial growth factor(VEGF)in rats with collagen-induced arthritis(CIA).Methods:Sixty clean-grade female Wistar rats were randomly divided into a blank control group,a model control group,a methotrexate group,and low,medium and high-dose Rebikang Tang groups,10 rats in each group.Except the blank control group,the rats in the other groups were induced by the incomplete adjuvant combined with collagen type Ⅱ to establish CIA rat models.The model control group was given intragastric administration of physiological saline,the low,medium and high-dose Rebikang Tang groups were given corresponding dose of Rebikang Tang,the methotrexate group was given intragastric administration of methotrexate and the rats in the control group could drink water and eat food freely.The effects of different doses of Rebikang on joint swelling index and VEGF were observed.Results:The joint swelling indexes in each dose of Rebikang group and the methotrexate group were lower than that of the model group(P < 0.01),among which the effect in the medium-dose Rebikang group was equivalent to that of the methotrexate group(P > 0.05) and the effect in the high-dose Rebikang group was superior to that of the methotrexate group(P < 0.01).The synovial VEGF levels in each Rebikang group and the methotrexate group were lower than that of the model control group(P < 0.05),among which the effect of the high-dose Rebikang group is superior to the methotrexate(P < 0.05),while the effects of the middle and low-dose Rebikang groups were equivalent to the methotrexate(P > 0.05).Conclusion:The mechanism of Rebikang Tang in the treatment of rheumatoid arthritis can be achieved by inhibiting the generation of VEGF.
引文
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[6]Grosios K,Wood J,Esser R,et al.Angiogenesis inhibitionby the novel VEGF receptor tyrosine kinase inhibitor,PTK787/ZK222584,causes significant anti-arthriticeffects in models of rheumatoid arthritis[J].InflammRes,2004,53(4):133-142.
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[8]庞学丰,龙朝阳,刘欢,等.热痹康汤对胶原诱导性关节炎大鼠血清TNF-α及IL-6的影响[J].广西中医药,2012,35(2):51-52.
[9]刘欢,庞学丰,吴燕红,等.热痹康汤对胶原诱导性关节炎大鼠血清IL-1β及IL-4的影响[J].江西中医学院学报,2012,2(1):55-57.
[10]庞学丰,蒙宇华,刘欢,等.热痹康汤对胶原诱导性关节炎大鼠滑膜P38/NF-κB信号通路的影响[J].风湿病与关节炎,2016,5(10):5-7,11.
[11]刘欢,庞学丰.热痹康汤对实验性关节炎大鼠血清IL-2及IL-10的影响[J].广西中医药,2010,33(1):48-50.
[12]庞学丰,李玉玲,刘欢,等.热痹康汤对胶原诱导性关节炎大鼠血清基质金属蛋白酶-3的影响[J].风湿病与关节炎,2013,2(4):32-34.
[2]邓安梅,仲人前,陈孙孝,等.关节炎中B7:CD28/CTLA-4共刺激途径的实验研究[J].中国免疫学杂志,2000,16(8):412-414.
[3]Shibuya M.Differential roles of vascular endothelialgrowth factor receptor-1 and receptor-2 in angiogenesis[J].J Biochem Mol Biol,2006,39(5):469-478.
[4]Clavel G,Bessis N,Lemeiter D,et al.Angiogenes ismarkers(VEGF,soluble receptor of VEGF and angiopoietin-1)in very early arthritis and their associationwith inflammation and joint destruction[J].ClinicalImmunol,2007,124(2):158-164.
[5]樊有龙,傅颖媛.类风湿关节炎患者AECA、VEGF、IL-17的检测及临床相关性研究[J].中国实验诊断学,2010,14(6):907-910.
[6]Grosios K,Wood J,Esser R,et al.Angiogenesis inhibitionby the novel VEGF receptor tyrosine kinase inhibitor,PTK787/ZK222584,causes significant anti-arthriticeffects in models of rheumatoid arthritis[J].InflammRes,2004,53(4):133-142.
[7]庞学丰,蒙宇华.热痹康胶囊治疗湿热型类风湿关节炎86例疗效观察[J].广州中医药大学学报,2003,20(2):106-108.
[8]庞学丰,龙朝阳,刘欢,等.热痹康汤对胶原诱导性关节炎大鼠血清TNF-α及IL-6的影响[J].广西中医药,2012,35(2):51-52.
[9]刘欢,庞学丰,吴燕红,等.热痹康汤对胶原诱导性关节炎大鼠血清IL-1β及IL-4的影响[J].江西中医学院学报,2012,2(1):55-57.
[10]庞学丰,蒙宇华,刘欢,等.热痹康汤对胶原诱导性关节炎大鼠滑膜P38/NF-κB信号通路的影响[J].风湿病与关节炎,2016,5(10):5-7,11.
[11]刘欢,庞学丰.热痹康汤对实验性关节炎大鼠血清IL-2及IL-10的影响[J].广西中医药,2010,33(1):48-50.
[12]庞学丰,李玉玲,刘欢,等.热痹康汤对胶原诱导性关节炎大鼠血清基质金属蛋白酶-3的影响[J].风湿病与关节炎,2013,2(4):32-34.