人参二醇组皂苷对再生障碍性贫血小鼠造血组织MAPK/ERK信号通路的诱导作用  

Panaxadiol saponins induce activation of MAPK/ERK signaling pathway in bone marrow cells of aplastic anemia mice

作　　者：张爱萍 高瑞兰[2] 尹利明[2] 罗梅宏 成志 夏乐敏 郑智茵[2] ZHANG Ai-ping;GAO Rui-lan;YIN Li-ming;LUO Mei-hong;CHENG Zhi;XIA Le-min;ZHENG Zhi-yin(Shanghai Baoshan Integrated Traditional Chinese and Western Medicine Hospital,Shanghai 201999,China;The First Affiliated Hospital of Zhejiang Chinese Medical University,Hangzhou 310006,China;The Second Affiliated Hospital of Zhejiang Chinese Medical University,Hangzhou 310003,China)

机构地区：[1]上海市宝山区中西医结合医院,上海201999 [2]浙江中医药大学附属第一医院,浙江杭州310006 [3]浙江中医药大学附属第二医院,浙江杭州310003

出　　处：《中国病理生理杂志》2018年第4期686-692,共7页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.81373876);浙江省中医药优秀青年人才基金资助项目(No.2014ZQ006)

摘　　要：目的:观察人参二醇组皂苷(PDS)对免疫介导型再生障碍性贫血(简称再障)小鼠骨髓细胞MAPK/ERK信号通路蛋白激酶及脾脏调节性T细胞的诱导作用,探讨其治疗再障的作用机制。方法:用[60Co]-γ射线5.0 Gy全身照射BALB/c小鼠,后经尾静脉输入DBA/2小鼠的淋巴细胞悬液,制备免疫介导型再障小鼠模型。60只小鼠随机分为6组,即正常组,模型组,PDS低、中、高剂量组,环孢素组。不同浓度药物灌胃治疗14 d测定各组小鼠外周血象,观察骨髓病理切片,Western blot法及免疫组织化学法测定骨髓细胞MEK1/2、p-MEK1/2、ERK1/2和p-ERK1/2的蛋白水平,流式细胞术检测脾脏调节性T细胞比例。结果:再障小鼠外周血全血细胞减少,骨髓呈抑制状态;PDS治疗能够显著升高再障小鼠外周血象,增加脾脏调节性T细胞比例,呈剂量依赖性(P<0.05)。PDS中、高剂量组显著上调骨髓细胞MEK1/2、p-MEK1/2、ERK1/2和p-ERK1/2的蛋白水平(P<0.05)。结论:PDS能有效促进造血,上调再障模型小鼠骨髓细胞MAPK/ERK信号通路多种蛋白激酶的表达,可能是PDS促进骨髓造血功能恢复的作用机制之一。另外,PDS对再障模型小鼠的免疫功能有一定的调节作用。AIM:To observe the effects of panaxadiol saponins(PDS)on up-regulation of MAPK/ERK signal pathway in bone marrow cells and increase in regulatory T(Treg)cells in spleen tissue of aplastic anemia(AA)mice,and to explore the mechanisms.METHODS:For preparation of immune-mediated AA model,BALB/c mice were exposed to sublethal dose(5.0 Gy)of[60 Co]-γradiation,followed by transplantation of lymphocytes from DBA/2 donor mice.BALB/c mice(n=60)were randomly divided into 6 groups,including normal mouse group,AA model group,PDS treatment groups at low,medium and high doses,and cyclosporine group as positive control.PDS and cyclosporine were given by gavage for 14 d.The peripheral blood cell counts and bone marrow pathological examination were tested.The protein levels of MEK1/2,p-MEK1/2,ERK1/2 and p-ERK1/2 in the bone marrow cells were analyzed by Western blot and immunohistochemistry experiment.Flow cytometry was used to detect the proportion of Treg cells in spleen tissue of each group.RESULTS:The peripheral blood cell counts were significantly decreased in AA mouse group as compared with normal mouse group(P<0.05).The bone marrow sections showed markedly inhibition status of hematopoiesis and the decrease in cellularity.In response to PDS treatment,the peripheral blood cell counts and Treg cells in the spleen tissues of AA mouse treated with PDS were significantly increased in a dose-dependent manner(P<0.05).Treatment with PDS at medium and high doses up-regulated the protein levels of MEK1/2,p-MEK1/2,ERK1/2 and p-ERK1/2 in the bone marrow of AA mice(P<0.05).CONCLUSION:PDS is effective to enhance recovery of hematopoietic function in AA mice.This effect may be related to up-regulating multiple protein kinases of MAPK/ERK signal pathway in the bone marrow cells of AA mice.In addition,PDS has an impact on immune function of AA mice.

关 键 词：人参二醇组皂苷 再生障碍性贫血 MAPK/ERK信号通路 

分 类 号：R556.5[医药卫生—血液循环系统疾病] R285.5[医药卫生—内科学]