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药效机制.docVIP

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药效机制 　　[摘要] 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TNFα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（RTPCR）法检测膝关节滑膜组织中JNK1，ERK1，p38的mRNA表?_。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TNFα的水平（P0.05）；给药4周，降低踝关节滑膜组织中p38，ERK1/2的蛋白表达（P0.05或P0.01），降低膝关节滑膜组织JNK1，p38，ERK1的基因表达（P0.05或P0.01）。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TNFα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。 　　[关键词] 五味甘露药浴散加减方； 佐剂型关节炎； TNFα； ERK1/2； JNK1； p38MAPK 　　Pharmacodynamic mechanism of modified Ganlu Yaoyu San intreatment of 　　rheumatoid arthritis based on MAPK signaling pathway 　　ZUO Fang， WEI Ting， TONG Dong， ZHANG Yi*， CHEN Xiaorui， ZENG Yong 　　（Chengdu University of Traditional Chinese Medicine， Chengdu 611137， China） 　　[Abstract] According to the findings， modified Ganlu Yaoyu San has a good antiinflammatory 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. Enzymelinked immune assay was used to determine the serum TNFα 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（RTPCR） method. According to the results， after administration for two weeks， the levels of serum TNFα of AA rat was significantly decreased（P0.05）. After administration for four weeks， the protein expressions of p38 and ERK1/2 in synovial tissue were reduced（P0.05 or P0.01）， the gene expressions of JNK1， p38 and ERK1 in knee joint synovial tissue were reduced（P0.05 or P0.01）. In conclusion， modified G