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机构地区:[1]淄博市中医医院,山东淄博255300 [2]北京中医药大学东直门医院,北京100700 [3]首都医科大学附属北京中医医院,北京100010
出 处:《中华中医药杂志》2016年第2期704-707,共4页China Journal of Traditional Chinese Medicine and Pharmacy
基 金:国家自然科学基金项目(No.81072770)~~
摘 要:目的:研究益肾达络饮对实验性自身免疫性脑脊髓炎(EAE)小鼠ERK1/2通路的影响。方法:将60只雌性SJL小鼠随机分为5组,即正常组、模型组、中药组、西药组和PD98059组,每组各12只。模型组、中药组、西药组和PD98059组分两点皮下注射抗原乳剂共200μL(含PLP139-151 150μg、H37Ra 400μg);分别在造模第1天、第3天再给予每只小鼠尾静脉注射百日咳杆菌液100μL(含百日咳杆菌0.6×106个)。造模第7天给予相应药物治疗,共干预15d,免疫后每天记录各组小鼠的神经功能评分。用Western blot法测定EAE小鼠脑组织内Ras、p-c-Raf、c-Raf、p-MEK1/2、MEK1/2、p-ERK1/2和ERK1/2的表达。结果:与模型组比较,中药组、西药组和PD98059组EAE小鼠第21天的神经功能评分显著降低(P<0.05)。模型组p-c-Raf、p-MEK1/2和p-ERK1/2的表达水平显著高于正常组(P<0.05);中药组、西药组和PD98059组p-c-Raf、p-MEK1/2和p-ERK1/2的表达水平显著低于模型组(P<0.05)。各组Ras、c-Raf、MEK1/2和ERK1/2的表达水平无显著差异。结论:益肾达络饮可通过降低p-MEK1/2和p-ERK1/2的表达抑制ERK1/2通路的激活,从而降低EAE小鼠的神经功能评分,延迟发病时间,但益肾达络饮抑制ERK1/2通路后引起的下游生物学效应尚不明确,需进一步研究。Objective:To study the effect of Yishen Daluo Decoction on ERK1/2 pathway in the mice with experimental autoimmune encephalomyelitis(EAE).Methods:Sixty female SJL mice were randomly divided into 5 groups:normal,model,Chinese medicine(CM),western medicine(WM) and PD98059 group,12 mice per each group.Each mouse in the model,CM,WM and PD98059 group was injected subcutaneously with 200 uL emulsion including 150 ug PLP139-151 and 400 ug H37Ra at two different sites of epigastrium on the first day 0.6×10~6 Bordetella pertussis in 100μL of saline was injected twice by caudal vein,first at the time of the PLP immunization and at the second time 48 hours later.The neurological deficit score was recorded after the PLP immunization.Western blot was used to detect the expression of Ras,p-c-Raf,c-Raf,p-MEK1/2,MEK1/2,p-ERK1/2and ERK1/2.Results:The neurological deficit score was reduced in EAE mice of CM,WM and PD98059 group by comparison to model group(P〈0.05).The expression of p-c-Raf,p-MEK1/2 and p-ERK1/2 in the model group was increased,compared with the normal group(P〈0.05).The expression of p-MEK1/2 and p-ERK1/2 of CM,WM and PD98059 group was lower than that of model group(P〈0.05).There were no differences in the expression of Ras,c-Raf,MEK1/2 and ERK1/2 among the five groups.Conclusion:Yishen Daluo Decoction could reduce mean neurological deficit score and delay the onset of EAE by decreasing the expression of p-MEK1/2 and p-ERK1/2 which in turn inhibit the activation of ERK1/2 pathway.But the downstream biological effects induced by Yishen Daluo Decoction inhibiting the ERK1/2 pathway should be needed to further study.
关 键 词:实验性自身免疫性脑脊髓炎 益肾达络饮 细胞外信号调节激酶1/2
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