补肾固冲方逆转Th1/Th2亚群失衡治疗URSA作用与机制研究  

Study of effect and molecule mechanism of Bushen Guchong decoction on URSA treatment by revising Th1 /Th2 shift

作　　者：彭莉[1] 赖楠楠 王东梅[1,3] 郭菲[1,3] 王丽[1,2] 郭钰琪[1,2] 姚成芳[1,2] 张洪海[1,2] 李霞(指导)[1,2] 

机构地区：[1]山东省医学科学院基础医学研究所,济南大学山东省医学科学院医学与生命科学学院,山东省肿瘤医院,济南250117 [2]山东省医学科学院基础医学研究所,山东省医药卫生肿瘤免疫与中药免疫重点实验室,山东省罕少见病重点实验室,卫生部生物技术药物重点实验室,国家中医药管理局免疫药理(三级)实验室,山东省免疫生物靶向药物工程技术中心,济南250062 [3]山东中医药大学附属医院,济南250014

出　　处：《中国免疫学杂志》2014年第10期1334-1338,1343,共6页Chinese Journal of Immunology

基　　金：国家自然科学基金项目(No.81373670);山东省自主创新成果转化专项(2013ZHZX2A0405);山东省博士基金项目(No.BS2009YY041);山东省科技发展计划项目(No.2012GSF11840);山东省自然科学基金项目(No.ZR2010HQ066);山东省计生委项目(No.[2009]8);山东省中管局项目(2013-216,2013-218);济南市科技明星计划项目(济科合字2012)

摘　　要：目的:探讨Th1/Th2亚群失衡在原因不明性复发性自然流产(URSA)中的作用及补肾固冲方逆转Th1/Th2亚群失衡治疗URSA的作用及分子机制。方法:URSA患者30例,给予补肾固冲方治疗,正常妊娠妇女30例为正常对照组,流式细胞术胞内外双染色法检测URSA患者治疗前后及正常妊娠妇女外周血Th1/Th2亚群分化状态,RT-PCR法检测Th1亚群特异性核转录因子T-bet、Th2亚群特异性核转录因子GATA-3mRNA转录水平。结果:与正常妊娠妇女比较,URSA患者外周血Th1亚群比例显著升高(P<0.05),Th2亚群比例显著降低(P<0.05),Th1/Th2比率显著升高(P<0.05)。补肾固冲方治疗后,URSA患者Th1亚群比例及T-bet转录水平显著降低(P<0.05),Th2亚群比例及GATA-3转录水平显著升高(P<0.05),Th1/Th2比率明显降低(P<0.05)。相关性分析显示,URSA患者治疗后子宫出血天数与Th1亚群比例呈显著正相关(P<0.05),与Th2亚群比例呈负相关,与Th1/Th2亚群呈正相关。结论:URSA患者存在Th1/Th2亚群失衡,补肾固冲方通过上调T-bet转录水平、下调GATA-3转录水平,优势诱导Th2亚群分化,逆转Th1/Th2亚群失衡,进而治疗URSA。Objective：To investigate the role of Th1/Th2 shift in unexplained recurrent spontaneous abortion（URSA） and to study the effect and molecular mechanism of Bushen Guchong decoction on URSA treatment by regulating Th1 /Th2 paradigm. Methods： 30 cases of URSA patients were given Bushen Guchong decoction administration; meanwhile,30 cases of normal pregnancy women were taken as control group. Th1 /Th2 paradigm in peripheral blood monocytes of URSA patients before and after Bushen Guchong decoction administration was detected by flow cytometry. Moreover,the mRNA expression of the specific transcription factors for Th1 and Th2 subsets- T-bet and GATA-3 were detected by RT-PCR assay. Furthermore,the relationship between the Th1 /Th2 paradigm and the uterine bleeding time after Bushen Guchong decoction administration was analyzed by Pearson correlation and regression tests. Results： Compared with normal pregnancy women,the proportion of Th1 subset of URSA patients was increased significantly（P〈0. 05）,while the proportion of Th2 subset was decreased markedly（P〈0. 05）. Additionally,the ration of Th1 /Th2 subsets was increased in URSA women（P〈0. 05）. After Bushen Guchong decoction treatment,the proportion of Th1 subsets in URSA patients and T-bet mRNA expression were up-regulated significantly（ P〈0. 05）,whereas the Th2 proportion and GATA-3 mRNA expression were down-regulated obviously（P〈0. 05）. Moreover,the ratio of Th1 /Th2 was decreased significantly（P〈0. 05）. Correlation analysis showed that the uterine bleeding time was positively related to both the proportion of Th1 and the ratio of Th1 /Th2,while negatively related to the proportion of Th2 subsets. Conclusion： Th1 /Th2 shift was involved in URSA. Bushen Guchong decoction up-regulated the transcription level of GATA-3 and down-regulated the transcription level of T-bet. Thereby,Bushen Guchong decoction exerted the curative effect on URSA by revising Th1 /Th2 shift.

关 键 词：原因不明性复发性自然流产 补肾固冲方 TH1 TH2 特异性核转录因子 

分 类 号：R392.5[医药卫生—免疫学]