中国中药杂志

2017, v.42(07) 1245-1250

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基于MAPK通路研究五味甘露药浴散加减方治疗类风湿关节炎的药效机制
Pharmacodynamic mechanism of modified Ganlu Yaoyu San intreatment of rheumatoid arthritis based on MAPK signaling pathway

左芳;韦婷;童东;张艺;陈小睿;曾勇;
ZUO Fang;WEI Ting;TONG Dong;ZHANG Yi;CHEN Xiao-rui;ZENG Yong;Chengdu University of Traditional Chinese Medicine;

摘要(Abstract):

研究发现五味甘露药浴散加减方药浴有良好的抗炎活性,可以明显改善关节炎症程度,对类风湿性关节炎具有一定的治疗作用,推测其可能与调控滑膜细胞MAPK通路有关。该实验通过建立佐剂关节炎大鼠(AA)模型,进一步探讨其调控滑膜细胞MAPK通路的机制。采用酶联免疫法测定给药2周AA大鼠血清中TNF-α的水平,免疫组化法测定给药4周踝关节滑膜组织蛋白激酶ERK1/2,p38的含量,采用荧光定量PCR(RT-PCR)法检测膝关节滑膜组织中JNK1,ERK1,p38的mRNA表达。结果显示,与模型组比较,给药2周,可明显降低AA大鼠血清中TNF-α的水平(P<0.05);给药4周,降低踝关节滑膜组织中p38,ERK1/2的蛋白表达(P<0.05或P<0.01),降低膝关节滑膜组织JNK1,p38,ERK1的基因表达(P<0.05或P<0.01)。综上可见,五味甘露药浴散加减方有效治疗类风湿关节炎的作用机制可能与其降低血清中TNF-α的水平和滑膜组织中p38,ERK1/2的表达以及JNK1,p38,ERK1的基因表达,调控MAPK通路有关。
According to the findings,modified Ganlu Yaoyu San has a good anti-inflammatory activity,and can significantly alleviate the degree of arthritis.Its therapeutic effect for rheumatoid arthritis may be related to the regulation of MAPK pathway of synovial cells.In the study,the rat adjuvant arthritis(AA) model was established to further investigate the pharmacodynamic mechanism for regulating MAPK pathway of synovial cells.Enzyme-linked immune assay was used to determine the serum TNF-α level of AA rats administered with drug for two weeks,synovial tissue protein kinases ERK1/2 and p38 content were determined by immunohistochemistry,synovial tissue JNK1,ERK1,p38 gene(mRNA) expression were detected with fluorescence quantitative PCR(RT-PCR) method.According to the results,after administration for two weeks,the levels of serum TNF-α of AA rat was significantly decreased(P<0.05).After administration for four weeks,the protein expressions of p38 and ERK1/2 in synovial tissue were reduced(P<0.05 or P<0.01),the gene expressions of JNK1,p38 and ERK1 in knee joint synovial tissue were reduced(P<0.05 or P<0.01).In conclusion,modified Ganlu Yaoyu San can effectively treat rheumatoid arthritis.Its mechanism might be related to the reduction of TNF-α levels in serum,protein expression of p38 and ERK1/2 in synovial tissue,and JNK1,p38 and ERK1 gene expressions,and regulation of MAPK pathway.

关键词(KeyWords): 五味甘露药浴散加减方;佐剂型关节炎;TNF-α;ERK1/2;JNK1;p38-MAPK
modified Ganlu Yaoyu San;adjuvant arthritis;TNF-α;ERK1/2;JNK1;p38-MAPK

Abstract:

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基金项目(Foundation): 国家自然科学基金地区科学基金项目(81260672);; 四川省科技厅省青年科技创新研究团队专项(2014TD0007)

作者(Author): 左芳;韦婷;童东;张艺;陈小睿;曾勇;
ZUO Fang;WEI Ting;TONG Dong;ZHANG Yi;CHEN Xiao-rui;ZENG Yong;Chengdu University of Traditional Chinese Medicine;

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