摘要
目的探讨川芎嗪对胶原诱导型关节炎大鼠细胞外调节蛋白激酶(extracellular regulated protein kinase,ERK)通路的影响。方法30只SPF级雄性SD大鼠随机分为对照组、模型组和川芎嗪组,每组10只。对模型组和川芎嗪组大鼠进行胶原诱导型关节炎造模,造模成功后川芎嗪组每日给予川芎嗪(0.1 g/kg),连续灌胃给药28 d;模型组、正常组给予相同体积生理盐水。每周测量3组大鼠的后足体积变化情况,采用HE染色法观察各组大鼠炎性细胞浸润情况,并采用实时荧光定量PCR和ELISA法检测大鼠滑膜组织及血清中肿瘤坏死因子α(tumor necrosis factorα,TNF-α)、血管生成素1(angiopoietin 1,Ang-1)、白细胞介素1β(interleukin1β,IL-1β)和血管内皮生长因子(vascular endothelial growth factor,VEGF)水平,以及采用蛋白质印迹法检测大鼠滑膜组织中ERK通路相关蛋白的表达水平。结果造模后第2周开始,模型组大鼠后足体积显著大于对照组(P<0.05),川芎嗪组大鼠后足体积与模型组同时间点比较显著降低(P<0.05);同时模型组和川芎嗪组大鼠血清和滑膜组织中炎性因子TNF-α、Ang-1、IL-1β及其mRNA表达水平均比对照组大鼠明显升高(P<0.05);川芎嗪组大鼠滑膜组织中VEGF水平相比模型组降低(P<0.05);模型组和川芎嗪组大鼠磷酸化ERK1/2(p-ERK1/2)蛋白表达水平均升高(P<0.05),但川芎嗪组大鼠p-ERK1/2蛋白表达水平明显低于模型组(P<0.05)。结论川芎嗪可能通过有效抑制ERK通路,调节胶原诱导型关节炎大鼠血清和滑膜组织中TNF-α、IL-1β水平,缓解关节肿胀症状。
Objective To investigate the effects of tetramethylpyrazine(TMP)on the extracellular regulated protein kinase(ERK)pathway in collagen-induced arthritis rats.Methods Thirty male SD rats were randomly divided into control group,model group and TMP group,with 10 rats in each group.The rats in the model group and the TMP group were modeled with collagen-induced arthritis.After the successful modeling,the TMP group was treated daily with TMP(0.1 g/kg)by intragastric administration,for continuous 28 d.The model group and the normal group were given the same volume of physiological saline.The volume changes of the hind paws in the three groups were measured weekly,and the inflammatory cell infiltration of each group was observed by HE staining.The levels of tumor necrosis factor α(TNF-α),angiopoietin 1(Ang-1),interleukin 1β(IL-1β)and vascular endothelial growth factor(VEGF)in synovial tissue and serum of rats were detected by realtime PCR and ELISA,respectively.The expressions of ERK pathway-related proteins in synovial tissues were detected by Western blotting.Results From the second week after modeling,the hind paw volume in the model group was higher than that in the control group(P<0.05),and the one in the TMP group was lower than that in the model group(P<0.05).The expression levels of inflammatory factors TNF-α,Ang-1 and IL-1β in the model group and the TMP group were higher than those in the control group(P<0.05),but the ones in the TMP group were lower than those in the model group(P<0.05).The level of VEGF in the synovial tissue of rats in the TMP group was lower than that of the model group(P<0.05).The expression of p-ERK1/2 protein in the model group and the TMP group was increased(P<0.05),and the expression level of p-ERK1/2 protein in the TMP group was lower than that of the model group(P<0.05).Conclusion TMP can effectively regulate the levels of TNF-α and IL-1β in serum and synovial tissue of rats with collagen-induced arthritis and alleviate the symptoms of joint swelling by inhibiting the ERK pathway.
作者
梁锦峰
刘文华
鄢宏
邓少杰
LIANG Jinfeng;LIU Wenhua;YAN Hong;DENG Shaojie(Department of Orthopedic,Shenzhen Baoan District People's Hospital,Shenzhen 518100,China;Department of Bone and Joint Surgery,Shenzhen 518000,China)
出处
《实验动物与比较医学》
CAS
2020年第5期391-396,共6页
Laboratory Animal and Comparative Medicine
关键词
川芎嗪
胶原诱导型关节炎
细胞外信号调节激酶通路
炎性因子
大鼠
Tetramethylpyrazine
Collagen-induced arthritis
Extracellular regulated protein kinase pathway
Inflammatory factor
Rats
