熊果酸对大鼠CIA模型关节TNF-α、IL-17、PGE2表达的影响
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摘要
目的探讨熊果酸(UA)对胶原诱导性关节炎(CIA)模型大鼠关节中TNF-α、IL-17、PGE2表达的影响。方法首先随机选取8只作为正常对照组,其余复制SD大鼠CIA模型,造模成功后随机分为模型对照组、熊果酸组、甲氨蝶呤组、地塞米松组并给予相应处理。于给药35天后处死大鼠,取关节制作切片,进行HE染色,观察关节骨质的病理改变,免疫组化法检测关节中炎症因子TNF-α、IL-17、PGE2的表达。结果与CIA模型组比较,UA大鼠组关节炎症因子TNF-α、IL-17、PGE2的表达明显降低(P<0.01),UA组效果不如甲氨蝶呤组、地塞米松组(P<0.01)。结论 UA能明显缓解CIA大鼠关节炎症及损伤,减少关节中相关炎症因子的表达。
Objective To investigate the effect of ursolic acid(UA) on the expression of TNF-α, IL-17 and PGE2 in the joints of rats with collagen-induced arthritis(CIA). Methods Eight rats as normal control group were randomly selected from the 60 SD rats, and the other rats were built for CIA models. Then the CIA models were randomly divided into model control group, ursolic acid group, methotrexate group and dexamethasone group. The rats were sacrificed 35 days after the administration, and the sections were harvested for HE staining to observe the pathological changes of the joint bone. The expression of inflammatory cytokines TNF-α, IL-17 and PGE2 were detected by immunohistochemistry. Results Compared with CIA model group, the expression of inflammatory factors TNF-α, IL-17 and PGE2 in UA rats significantly decreased(P<0.01), and the effects of UA were not as good as those in methotrexate and dexamethasone groups(P<0.01). Conclusion UA can significantly relieve the inflammation and injury of joints in CIA rats and reduce the expression of related inflammatory factors in the joints.
Objective To investigate the effect of ursolic acid(UA) on the expression of TNF-α, IL-17 and PGE2 in the joints of rats with collagen-induced arthritis(CIA). Methods Eight rats as normal control group were randomly selected from the 60 SD rats, and the other rats were built for CIA models. Then the CIA models were randomly divided into model control group, ursolic acid group, methotrexate group and dexamethasone group. The rats were sacrificed 35 days after the administration, and the sections were harvested for HE staining to observe the pathological changes of the joint bone. The expression of inflammatory cytokines TNF-α, IL-17 and PGE2 were detected by immunohistochemistry. Results Compared with CIA model group, the expression of inflammatory factors TNF-α, IL-17 and PGE2 in UA rats significantly decreased(P<0.01), and the effects of UA were not as good as those in methotrexate and dexamethasone groups(P<0.01). Conclusion UA can significantly relieve the inflammation and injury of joints in CIA rats and reduce the expression of related inflammatory factors in the joints.
引文
[1]邝涛,李鑫,王宝新,等.湖南地区类风湿关节炎中医证型与临床检测指标关系研究[J].湖南中医药大学学报,2017,37(7):745-748.
[2]孟英才,詹济华,肖水平,等.熊果酸衍生物的合成及其抗菌活性评价[J].湖南中医药大学学报,2017,37(5):493-498.
[3]LUO J,HU YL,WANG H.Ursolic acid inhibits breast cancer growth by inhibiting proliferation,inducing autophagy and apoptosis,and suppressing inflammatory responses via the PI3K/AKT and NF-κB signaling pathways in vitro[J].Exp Ther Med,2017,14(4):3623-3631.
[4]KASHYAP D,TULI H S,SHARMA A K.Ursolic acid(UA):A metabolite with promising therapeutic potential[J].Life Sci,2016,146:201-13.
[5]WOZNIAK L,SKAPSKA S,MARSZA覥ek K.Ursolic acid-a pentacyclic triterpenoid with a wide spectrum of pharmacological activities[J].Molecules,2015,20:20614-20641.
[6]KONG L,LI S,LIAO Q,et al.Oleanolic acid and ursolic acid:novel hepatitis C virus antivirals that inhibit NS5B activity[J].Antiviral Res.2013,98(1):44-53.
[7]WANG X H,ZHOU S Y,QIAN Z Z,et al.Evaluation of toxicity and single-dose pharmacokinetics of intravenous ursolic acid liposomes in healthy adult volunteers and patients with advanced solid tumors[J].Expert Opin Drug Metab Toxicol,2013,9(2):117-125.
[8]NELSON A T,CAMELIO A M,CLAUSSEN K R,et al.Synthesis of oxygenated oleanolic and ursolic acid derivatives with antiin flammatory properties[J].Bioorg Med Chem Lett,2015,25:4342-4346.
[9]孔薇.Ⅱ型胶原诱导关节炎大鼠模型的制备、评价及部分机制的研究[D].合肥:安徽医科大学,2008.
[10]BETTELLI E,CARRIER Y,GAO W,et al.Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells[J].Nature,2006,441(7090):235-238.
[11]HONORATI MC,NERI S,CATTINI L,et al.Interleukin-17,a regulator of angiogenic factor release by synovial fibroblasts[J].Osteoarthritis Cartilage,2006,14(4):345-352.
[12]COOLES F A,ISAACS J D.Pathophysiology of rheumatoid arthritis[J].Curr Opin Rheumatol,2011,23(3):233-240.
[13]VAN L G,BEYAERT R.Negative regulation of NF-kappa B and its involvement in rheumatoid arthritis[J].Arthritis Res Ther,2011,13(3):221.
[14]陈纪藩,叶柳忠,陈光星,等.通痹灵对CIA大鼠关节软骨病变影响的实验研究[J].中国中医基础医学杂志,2003,9(5):32-35.
[15]陈纪藩,叶柳忠,陈光星,等.通痹灵对胶原诱导性关节炎大鼠软骨破坏的对抗作用[J].广州中医药大学学报,2003,20(1):8-12,91.
[16]曹艳红,胡建东.湿热痹阻与寒湿痹阻型类风湿关节炎相关细胞因子客观化研究[J].湖南中医药大学学报,2016,36(10):61-71.
[17]曾光,梁清华,吴汉军,等.熊果酸对刀豆蛋白A诱导小鼠T细胞增殖与激活的影响[J].湖南中医药大学学报,2008,28(2):16-18.
[18]ZENG G,LIANG Q H,YOU W H,et al.Ursolic acid inhibits T cell activation through modulating NF-кB signaling[J].Chinese Journal of Integrative Medicine,2012,18(1):34-37.
[19]曾光,陈芳,熊新贵,等.熊果酸对CIA大鼠关节炎症及骨质破坏的影响[J].湖南中医药大学学报,2013,33(7):3-7.
[2]孟英才,詹济华,肖水平,等.熊果酸衍生物的合成及其抗菌活性评价[J].湖南中医药大学学报,2017,37(5):493-498.
[3]LUO J,HU YL,WANG H.Ursolic acid inhibits breast cancer growth by inhibiting proliferation,inducing autophagy and apoptosis,and suppressing inflammatory responses via the PI3K/AKT and NF-κB signaling pathways in vitro[J].Exp Ther Med,2017,14(4):3623-3631.
[4]KASHYAP D,TULI H S,SHARMA A K.Ursolic acid(UA):A metabolite with promising therapeutic potential[J].Life Sci,2016,146:201-13.
[5]WOZNIAK L,SKAPSKA S,MARSZA覥ek K.Ursolic acid-a pentacyclic triterpenoid with a wide spectrum of pharmacological activities[J].Molecules,2015,20:20614-20641.
[6]KONG L,LI S,LIAO Q,et al.Oleanolic acid and ursolic acid:novel hepatitis C virus antivirals that inhibit NS5B activity[J].Antiviral Res.2013,98(1):44-53.
[7]WANG X H,ZHOU S Y,QIAN Z Z,et al.Evaluation of toxicity and single-dose pharmacokinetics of intravenous ursolic acid liposomes in healthy adult volunteers and patients with advanced solid tumors[J].Expert Opin Drug Metab Toxicol,2013,9(2):117-125.
[8]NELSON A T,CAMELIO A M,CLAUSSEN K R,et al.Synthesis of oxygenated oleanolic and ursolic acid derivatives with antiin flammatory properties[J].Bioorg Med Chem Lett,2015,25:4342-4346.
[9]孔薇.Ⅱ型胶原诱导关节炎大鼠模型的制备、评价及部分机制的研究[D].合肥:安徽医科大学,2008.
[10]BETTELLI E,CARRIER Y,GAO W,et al.Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells[J].Nature,2006,441(7090):235-238.
[11]HONORATI MC,NERI S,CATTINI L,et al.Interleukin-17,a regulator of angiogenic factor release by synovial fibroblasts[J].Osteoarthritis Cartilage,2006,14(4):345-352.
[12]COOLES F A,ISAACS J D.Pathophysiology of rheumatoid arthritis[J].Curr Opin Rheumatol,2011,23(3):233-240.
[13]VAN L G,BEYAERT R.Negative regulation of NF-kappa B and its involvement in rheumatoid arthritis[J].Arthritis Res Ther,2011,13(3):221.
[14]陈纪藩,叶柳忠,陈光星,等.通痹灵对CIA大鼠关节软骨病变影响的实验研究[J].中国中医基础医学杂志,2003,9(5):32-35.
[15]陈纪藩,叶柳忠,陈光星,等.通痹灵对胶原诱导性关节炎大鼠软骨破坏的对抗作用[J].广州中医药大学学报,2003,20(1):8-12,91.
[16]曹艳红,胡建东.湿热痹阻与寒湿痹阻型类风湿关节炎相关细胞因子客观化研究[J].湖南中医药大学学报,2016,36(10):61-71.
[17]曾光,梁清华,吴汉军,等.熊果酸对刀豆蛋白A诱导小鼠T细胞增殖与激活的影响[J].湖南中医药大学学报,2008,28(2):16-18.
[18]ZENG G,LIANG Q H,YOU W H,et al.Ursolic acid inhibits T cell activation through modulating NF-кB signaling[J].Chinese Journal of Integrative Medicine,2012,18(1):34-37.
[19]曾光,陈芳,熊新贵,等.熊果酸对CIA大鼠关节炎症及骨质破坏的影响[J].湖南中医药大学学报,2013,33(7):3-7.