川芎嗪对CIA大鼠足爪组织MMP-13蛋白表达及血清VEGF、IL-17和IL-23水平的影响
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摘要
目的:探讨川芎嗪(tetramethylpyrazine,TMP)治疗胶原性关节炎(collagen-induced arthritis,CIA)大鼠的可能机制。方法:采用Ⅱ型胶原诱导CIA大鼠模型。随机分为正常对照组、模型组与药物处理组,用免疫组化染色法和Western blotting分析检测足爪组织中基质金属蛋白酶(MMP)-13蛋白的表达;HE染色观察不同剂量的TMP对CIA大鼠足爪组织病理学变化的影响;ELISA法检测CIA大鼠血清中VEGF、IL-17和IL-23的含量。结果:与CIA组相比,CIA+TMP(100 mg.kg-1)组大鼠体重明显回升(P<0.01),足爪组织胞浆中MMP-13蛋白表达降低了31.82%(P<0.01),大鼠足爪皮下组织病理改变明显减轻,血清中VEGF、IL-17和IL-23的含量分别降低了33.33%、27.40%和33.33%(P<0.01)。结论:TMP(100 mg.kg-1)对CIA大鼠炎症有明显的抑制作用,其机制可能与其下调MMP-13蛋白表达,抑制炎症细胞浸润及血管增生,降低VEGF、IL-17和IL-23的产生有关。
AIM: To investigate the mechanism of tetramethylpyrazine(TMP) in treating collagen-induced arthritis(CIA) in rats.METHODS: The rat model of type II collagen-induced arthritis was established and the rats were randomly divided into normal control group,CIA group and TMP treatment group.The protein expression of matrix metalloproteinase 13(MMP-13) in paw tissues was detected by immunohistochemical staining and Western blotting.The histopathological changes of the skin in the rat paws were observed with HE staining.The levels of vascular endothelial growth factor(VEGF),interleukin 17(IL-17) and interleukin 23(IL-23) in the serum of CIA rats were detected by ELISA.RESULTS: Compared with CIA group,TMP at a dose of 100 mg /kg significantly reduced the weight loss in CIA rats and decreased the protein expression of MMP-13 by 31.82%.TMP also attenuated the pathological changes of the paw subcutaneous tissues.TMP obviously decreased the levels of VEGF by 33.33%,IL-17 by 27.40% and IL-23 by 33.33% in the serum.CONCLUSION: TMP significantly inhibits the development of CIA by decreasing the protein expression of MMP13,inhibiting the inflammatory cell infiltration and vascular proliferation,and reducing the production of VEGF,IL-17 and IL-23 in CIA rats.
AIM: To investigate the mechanism of tetramethylpyrazine(TMP) in treating collagen-induced arthritis(CIA) in rats.METHODS: The rat model of type II collagen-induced arthritis was established and the rats were randomly divided into normal control group,CIA group and TMP treatment group.The protein expression of matrix metalloproteinase 13(MMP-13) in paw tissues was detected by immunohistochemical staining and Western blotting.The histopathological changes of the skin in the rat paws were observed with HE staining.The levels of vascular endothelial growth factor(VEGF),interleukin 17(IL-17) and interleukin 23(IL-23) in the serum of CIA rats were detected by ELISA.RESULTS: Compared with CIA group,TMP at a dose of 100 mg /kg significantly reduced the weight loss in CIA rats and decreased the protein expression of MMP-13 by 31.82%.TMP also attenuated the pathological changes of the paw subcutaneous tissues.TMP obviously decreased the levels of VEGF by 33.33%,IL-17 by 27.40% and IL-23 by 33.33% in the serum.CONCLUSION: TMP significantly inhibits the development of CIA by decreasing the protein expression of MMP13,inhibiting the inflammatory cell infiltration and vascular proliferation,and reducing the production of VEGF,IL-17 and IL-23 in CIA rats.
引文
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[2]Abeles AM,Pillinger MH.The role of the synovial fibro-blast in rheumatoid arthritis:cartilage destruction and theregulation of matrix metalloproteinases[J].Bull NYU HospJt Dis,2006,64(1-2):20-24.
[3]徐晓玉,严鹏科,陈刚,等.川芎嗪对小鼠肺癌血管生长和VEGF表达抑制[J].中国药理学通报,2004,20(2):151-154.
[4]赵占胜,金玉怀,丛斌,等.八肽胆囊收缩素对TNF-α诱导的大鼠滑膜细胞株RSC-364IL-6的作用及其可能的分子机制[J].中国病理生理杂志,2007,23(7):1396-1401.
[5]王建竹,孔祥英,林娜.ERK信号转导通路与类风湿关节炎[J].中国病理生理杂志,2011,27(2):398-402.
[6]Nagashima M,Tanaka H,Takahashi H,et al.Study of themechanism involved in angiogenesis and synovial cell pro-liferation in human synovial tissues of patients with rheu-matoid arthritis using SCID mice[J].Lab Invest,2002,82(8):981-988.
[7]许建中,张晓强,刘占举.白细胞介素-23在类风湿关节炎滑膜中的表达及意义[J].中华风湿病学杂志,2007,11(2):96-98.
[8]Parham C,Chirica M,Timans J,et al.A receptor for theheterodimeric cytokine IL-23 is composed of IL-12Rβ1 anda novel cytokine receptor subunit,IL-23R[J].J lmmunol,2002,168(11):5699-5708.
[9]Kolls JK,Linden A.Interleukin-17 family members and in-flammation[J].Immunity,2004,21(4):467-476.
[10]Hwang SY,Kim JY,Kim KW,et al.IL-17 induces produc-tion of IL-6 and IL-8 in rheumatoid arthritis synovial fibro-blasts via NF-κB and PI3-kinase/Akt-dependent pathways[J].Arthritis Res Ther,2004,6(2):R120-R128.
[11]Shiozawa S,Tsumiyama K,Yoshida K,et al.Pathogenesisof joint destruction in rheumatoid arthritis[J].Arch Immu-nol Ther Exp(Warsz),2011,59(2):89-95.
[12]Kim KS,Choi HM,Oh DH,et al.Effect of taurine chlora-mine on the production of matrix metalloproteinases(MMPs)in adiponectin-or IL-1β-stimulated fibroblast-likesynoviocytes[J].J Biomed Sci,2010,17(Suppl 1):S27.