寿胎丸对复发性流产小鼠蜕膜蛋白质组影响的初步研究
|
摘要
目的：
分析寿胎丸对复发性流产小鼠蜕膜蛋白质组的影响,从分子水平探讨寿胎丸安胎的作用机制,为中医药防治复发性流产提供新的思路和理论依据。
方法：
1.复发性流产小鼠模型的制备及寿胎丸干预：CBA/J×BALB/C建立正常妊娠模型,CBA/J×DBA/2建立复发性流产模型,将复发性流产模型CBA/J×DBA/2孕鼠按怀孕先后顺序随机分为四组,分别为模型组、寿胎丸高剂量组、寿胎丸中剂量组和寿胎丸低剂量组,从妊娠第1天开始给药,孕14天后处死小鼠,计算各组胚胎丢失率。
2.复发性流产小鼠蜕膜蛋白质组学研究：应用固相pH梯度(IPG)2-DE技术分别分离模型组、正常组、寿胎丸高、中、低剂量组小鼠蜕膜组织总蛋白质后,经考染显色、PDQuest图像分析、识别差异表达的蛋白质点,应用基质辅助激光解吸电离飞行时间质谱技术(MALDI-TOF-MS)分析得到肽质量指纹图谱(PMF),再经Mascot软件搜索SWISS-PROT和NCBI蛋白质数据库鉴定蛋白质,并利用生物信息学资源对所鉴定蛋白质的功能进行分析。
3.差异蛋白质HSP27、α-enolase、Transferrin、Annexin A2结果验证：采用蛋白印迹和免疫组化方法对4个可能与复发性流产及寿胎丸作用相关的差异蛋白质HSP27、α-enolase、Transferrin、Annexin A2从蛋白水平的表达情况验证蛋白质组学鉴定结果的可靠性。
结果：
1.复发性流产小鼠模型的制备及寿胎丸干预：小鼠模型组与正常组相比,胚胎丢失率明显升高,差异有显著统计学意义(P<0.01)；寿胎丸高、中剂量组与模型组相比,胚胎丢失率均降低,差异有显著统计学意义(P<0.01)；寿胎丸低剂量组未能明显改善复发性流产小鼠胚胎丢失率,与模型组相比差异无统计学意义(P>0.05)。
2.复发性流产小鼠蜕膜蛋白质组学研究：建立了模型组、正常组、寿胎丸高、中、低剂量组小鼠蜕膜组织的2-DE图谱。PDQuest软件的分析结果显示,每张2-DE图谱约有800个蛋白质点,蛋白质分子量(Mw)主要集中在10-100KDa范围内,等电点(pI)主要分布在pH4.0-10.0之间。以模型组为参照,其余各组蛋白点与其匹配率为83%,表达差异3倍以上的蛋白点有60个,其中上调的点有28个,下调的点有32个。通过比较模型组、正常组、寿胎丸高、中、低剂量组双向凝胶电泳图谱的差异,发现并鉴定了30个可能与复发性流产及寿胎丸干预相关的蛋白质,这些蛋白质的功能涉及绒毛外滋养细胞的侵袭、蜕膜组织血管的重建及蜕膜细胞的凋亡等。
3.差异蛋白质HSP27、α-enolase、Transferrin、Annexin A2结果验证：蛋白印迹和免疫组化检测结果显示,小鼠模型组与正常组相比,蜕膜HSP27、α-enolase表达明显升高,Transfern、Annexin A2表达明显降低,差异有显著统计学意义(P<0.01)；寿胎丸高、中、低剂量组与模型组相比,蜕膜HSP27、α-enolase表达均降低,AnnexinA2表达均升高,差异有显著统计学意义(P<0.01)；寿胎丸高剂量组与模型组相比,蜕膜Transferrin表达升高,差异有显著统计学意义(P<0.01)；寿胎丸中、低剂量组与模型组相比,蜕膜Transferrin表达差异无统计学意义(P>0.05)。证实各实验组中HSP27、α-enolase、 Transferrin、Annexin A2于蛋白表达水平和2-DE结果相一致。
结论：
1.寿胎丸能够降低复发性流产小鼠模型的胚胎丢失率,具有显著的安胎作用。
2.成功建立了模型组、正常组、寿胎丸高、中、低剂量组的双向凝胶电泳(2-DE)图谱,鉴定了30个差异表达的蛋白质,提示复发性流产是一多种蛋白质参与的复杂过程,小鼠蜕膜组织的比较蛋白质组学分析是筛选复发性流产病变相关蛋白质的可靠方法之一；寿胎丸可调节复发性流产小鼠蜕膜组织多种蛋白质的表达,提示该复方具有多靶点的作用特点。
3.HSP27、α-enolase、Transferrin、Annexin A2的蛋白印迹和免疫组化验证结果与蛋白质组学分析结果一致,从一定程度上证明了蛋白质组学实验方法的稳定性及其结果的准确性；寿胎丸通过下调复发性流产小鼠蜕膜组织HSP27、α-enolase蛋白的表达,同时上调Transferrin、Annexin A2蛋白的表达,从而实现维持妊娠,降低胚胎丢失率,这可能是其安胎的作用机制之一。
Objective:
To analysis the differential expression of decidua tissue proteins and effective mechanisms of recurrent abortion mice with Shoutaiwan,and explore the mechanism of Shoutaiwan in preventing miscarriage, in order to provide a theoretical basis for better clinical applications of Shoutaiwan.
Method:
1.The preparation of recurrent abortion models and intervention with Shoutaiwan:The abortion-prone CBA/J X DBA/2matings were established as the model of spontaneous abortion and the nonabortion-prone CBA/J×BALB/c matings were used as the model of normal pregnancy.The model of spontaneous abortion CBA/J X DBA/2of mice pregnant were randomly divided into four groups according to the sequence of pregnancy.From the1st day of pregnant,pregnant rats of every group are oral administration indifferent doses. On the14th days of pregnancy,the mice are killed and the embryo resorption rate was counted.
2.Proteome analysis of decidua tissues in recurrent abortion mice:In the first place, the total proteins of mice decidua tissues at model group,normal group,low-dose Shoutaiwan group,middle-dose Shoutaiwan group and low-dose Shoutaiwan group, were separated by means of immobilized pH gradient(IPG)based2-DE and coomassie brilliant blue staining.The expression of differential protein spots was analyze by PDquest and then identified by matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS).The acquired Peptide mass fingerprints(PMFs)were used to search for matches in SWISS-PROT and NCBI databases with Mascot software.The functions of identified proteins were further analysed according to bioinformatics resources.
3.Validating of differential expression proteins pots of HSP27, α-enolase,Transferrin and Annexin A2:In order to validate the reliability of the identified proteome analysis results,the expression of4differential protein spots of HSP27, α-enolase,Transferrin and Annexin A2in protein levels,which maybe correlated with recurrent abortion and Shoutaiwan intervention, was detected by immunohistochemical and Western blot analysis.
Result:
1.The models of embryo resorption rate are higher than the normal pregnancy group,compared with model group,low-dose Shoutaiwan can not significantly improve the model of spontaneous abortion in pregnant mice embryo resorption rate(P>0.05);Shoutaiwan high-dose group of pregnant mice absorption rate of the embryos were significantly decreased(P<0.01).
2.Proteome analysis of decidua tissues in recurrent abortion mice:The results showed that the well-resolved,reproducible2-DE patterns of mice decidua tissues of recurrent abortion,model group,normal group,low-dose Shoutaiwan group,middle-dose Shoutaiwan group and low-dose Shoutaiwan group were obtained.Analysis by PDQuest software, there are800protein points in every decidua respectivly.2-DE Gel analysis shows protein molecular weight concentrated mainly on10-100KDa,iso electric point was mainly in range of pH4.0-10.0.As the standard with the model decidua,proteins matching rate is83%between every decidua.Protein points of the differential expression are60.Up-regulation protein points over three times are28,and down-regulation protein points over three times are32.Through comparative proteome analysis of decidua tissues of model group,normal group,low-dose Shoutaiwan group,middle-dose Shoutaiwan group and low-dose Shoutaiwan group,30differential expression protein spots which maybe related to recurrent abortion and Shoutaiwan intervention were identified by MS.These differential expression proteins mainly refer to invasion of the blastocyst, blood vessel remodeling and cell apoptosis.
3.Validating of differential expression proteins pots of HSP27, α-enolase,Transferrin and Annexin A2:Used the methods of Western blot and immunohistochemical,HSP27and α-enolase expression in model group are significantly higher than the normal pregnancy group(P< 0.01);Transferrin and Annexin A2expression,ara significantly lower than the normal pregnancy group at decidua tissues (P<0.01);Compared with model group,Shoutaiwan low middle high-dose group can decreased significantly HSP27and α-enolase expression in decidua tissues of pregnant mice(P<0.01);Shoutaiwan low middle high-dose group make Annexin A2expression in decidua tissues increased significantly(P<0.01);Compared with model group,Shoutaiwan high-dose group can increased significantly Transferrin in decidua tissues(P<0.01),Shoutaiwan middle low-dose group show no significant difference(P>0.05).These was consistent with our proteome analysis results.
Conclusion:
1.Shoutaiwan can decrease recurrent abortion mice absorption rate of the embryos significantly,and play a role in preventing miscarriage.
2.The2-DE reference maps of decidua tissues of mice including model group,normal group,low-dose Shoutaiwan group,middle-dose Shoutaiwan group and low-dose Shoutaiwan group were established successfully.30differential expression proteins pots were identified.It indicated that recurrent abortion is a complicated process refer to diverse proteins participate and the comparison proteome analysis was a reliable method to sieve related proteins pots for recurrent abortion pathological changes.For several proteins pots expression of decidua tissues in recurrent abortion mice was regulated by Shoutaiwan,it provides contribution to the effect characteristic of multitarget.
3.The expression of HSP27, α-enolase,Transferrin and Annexin A2in Protein levels with the methods of immunohistochemical and Western blot analysis was consistented with our proteome analysis results.Thus identificated the stability and reliable of proteome analysis.Shoutaiwan could down-regulate the expression of HSP27, α-enolase and up-regulate the expression of Transferrin,Annexin A2in protein levels,which may be one of the mechanisms of Shoutaiwans preventing miscarriage effect.
分析寿胎丸对复发性流产小鼠蜕膜蛋白质组的影响,从分子水平探讨寿胎丸安胎的作用机制,为中医药防治复发性流产提供新的思路和理论依据。
方法：
1.复发性流产小鼠模型的制备及寿胎丸干预：CBA/J×BALB/C建立正常妊娠模型,CBA/J×DBA/2建立复发性流产模型,将复发性流产模型CBA/J×DBA/2孕鼠按怀孕先后顺序随机分为四组,分别为模型组、寿胎丸高剂量组、寿胎丸中剂量组和寿胎丸低剂量组,从妊娠第1天开始给药,孕14天后处死小鼠,计算各组胚胎丢失率。
2.复发性流产小鼠蜕膜蛋白质组学研究：应用固相pH梯度(IPG)2-DE技术分别分离模型组、正常组、寿胎丸高、中、低剂量组小鼠蜕膜组织总蛋白质后,经考染显色、PDQuest图像分析、识别差异表达的蛋白质点,应用基质辅助激光解吸电离飞行时间质谱技术(MALDI-TOF-MS)分析得到肽质量指纹图谱(PMF),再经Mascot软件搜索SWISS-PROT和NCBI蛋白质数据库鉴定蛋白质,并利用生物信息学资源对所鉴定蛋白质的功能进行分析。
3.差异蛋白质HSP27、α-enolase、Transferrin、Annexin A2结果验证：采用蛋白印迹和免疫组化方法对4个可能与复发性流产及寿胎丸作用相关的差异蛋白质HSP27、α-enolase、Transferrin、Annexin A2从蛋白水平的表达情况验证蛋白质组学鉴定结果的可靠性。
结果：
1.复发性流产小鼠模型的制备及寿胎丸干预：小鼠模型组与正常组相比,胚胎丢失率明显升高,差异有显著统计学意义(P<0.01)；寿胎丸高、中剂量组与模型组相比,胚胎丢失率均降低,差异有显著统计学意义(P<0.01)；寿胎丸低剂量组未能明显改善复发性流产小鼠胚胎丢失率,与模型组相比差异无统计学意义(P>0.05)。
2.复发性流产小鼠蜕膜蛋白质组学研究：建立了模型组、正常组、寿胎丸高、中、低剂量组小鼠蜕膜组织的2-DE图谱。PDQuest软件的分析结果显示,每张2-DE图谱约有800个蛋白质点,蛋白质分子量(Mw)主要集中在10-100KDa范围内,等电点(pI)主要分布在pH4.0-10.0之间。以模型组为参照,其余各组蛋白点与其匹配率为83%,表达差异3倍以上的蛋白点有60个,其中上调的点有28个,下调的点有32个。通过比较模型组、正常组、寿胎丸高、中、低剂量组双向凝胶电泳图谱的差异,发现并鉴定了30个可能与复发性流产及寿胎丸干预相关的蛋白质,这些蛋白质的功能涉及绒毛外滋养细胞的侵袭、蜕膜组织血管的重建及蜕膜细胞的凋亡等。
3.差异蛋白质HSP27、α-enolase、Transferrin、Annexin A2结果验证：蛋白印迹和免疫组化检测结果显示,小鼠模型组与正常组相比,蜕膜HSP27、α-enolase表达明显升高,Transfern、Annexin A2表达明显降低,差异有显著统计学意义(P<0.01)；寿胎丸高、中、低剂量组与模型组相比,蜕膜HSP27、α-enolase表达均降低,AnnexinA2表达均升高,差异有显著统计学意义(P<0.01)；寿胎丸高剂量组与模型组相比,蜕膜Transferrin表达升高,差异有显著统计学意义(P<0.01)；寿胎丸中、低剂量组与模型组相比,蜕膜Transferrin表达差异无统计学意义(P>0.05)。证实各实验组中HSP27、α-enolase、 Transferrin、Annexin A2于蛋白表达水平和2-DE结果相一致。
结论：
1.寿胎丸能够降低复发性流产小鼠模型的胚胎丢失率,具有显著的安胎作用。
2.成功建立了模型组、正常组、寿胎丸高、中、低剂量组的双向凝胶电泳(2-DE)图谱,鉴定了30个差异表达的蛋白质,提示复发性流产是一多种蛋白质参与的复杂过程,小鼠蜕膜组织的比较蛋白质组学分析是筛选复发性流产病变相关蛋白质的可靠方法之一；寿胎丸可调节复发性流产小鼠蜕膜组织多种蛋白质的表达,提示该复方具有多靶点的作用特点。
3.HSP27、α-enolase、Transferrin、Annexin A2的蛋白印迹和免疫组化验证结果与蛋白质组学分析结果一致,从一定程度上证明了蛋白质组学实验方法的稳定性及其结果的准确性；寿胎丸通过下调复发性流产小鼠蜕膜组织HSP27、α-enolase蛋白的表达,同时上调Transferrin、Annexin A2蛋白的表达,从而实现维持妊娠,降低胚胎丢失率,这可能是其安胎的作用机制之一。
Objective:
To analysis the differential expression of decidua tissue proteins and effective mechanisms of recurrent abortion mice with Shoutaiwan,and explore the mechanism of Shoutaiwan in preventing miscarriage, in order to provide a theoretical basis for better clinical applications of Shoutaiwan.
Method:
1.The preparation of recurrent abortion models and intervention with Shoutaiwan:The abortion-prone CBA/J X DBA/2matings were established as the model of spontaneous abortion and the nonabortion-prone CBA/J×BALB/c matings were used as the model of normal pregnancy.The model of spontaneous abortion CBA/J X DBA/2of mice pregnant were randomly divided into four groups according to the sequence of pregnancy.From the1st day of pregnant,pregnant rats of every group are oral administration indifferent doses. On the14th days of pregnancy,the mice are killed and the embryo resorption rate was counted.
2.Proteome analysis of decidua tissues in recurrent abortion mice:In the first place, the total proteins of mice decidua tissues at model group,normal group,low-dose Shoutaiwan group,middle-dose Shoutaiwan group and low-dose Shoutaiwan group, were separated by means of immobilized pH gradient(IPG)based2-DE and coomassie brilliant blue staining.The expression of differential protein spots was analyze by PDquest and then identified by matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS).The acquired Peptide mass fingerprints(PMFs)were used to search for matches in SWISS-PROT and NCBI databases with Mascot software.The functions of identified proteins were further analysed according to bioinformatics resources.
3.Validating of differential expression proteins pots of HSP27, α-enolase,Transferrin and Annexin A2:In order to validate the reliability of the identified proteome analysis results,the expression of4differential protein spots of HSP27, α-enolase,Transferrin and Annexin A2in protein levels,which maybe correlated with recurrent abortion and Shoutaiwan intervention, was detected by immunohistochemical and Western blot analysis.
Result:
1.The models of embryo resorption rate are higher than the normal pregnancy group,compared with model group,low-dose Shoutaiwan can not significantly improve the model of spontaneous abortion in pregnant mice embryo resorption rate(P>0.05);Shoutaiwan high-dose group of pregnant mice absorption rate of the embryos were significantly decreased(P<0.01).
2.Proteome analysis of decidua tissues in recurrent abortion mice:The results showed that the well-resolved,reproducible2-DE patterns of mice decidua tissues of recurrent abortion,model group,normal group,low-dose Shoutaiwan group,middle-dose Shoutaiwan group and low-dose Shoutaiwan group were obtained.Analysis by PDQuest software, there are800protein points in every decidua respectivly.2-DE Gel analysis shows protein molecular weight concentrated mainly on10-100KDa,iso electric point was mainly in range of pH4.0-10.0.As the standard with the model decidua,proteins matching rate is83%between every decidua.Protein points of the differential expression are60.Up-regulation protein points over three times are28,and down-regulation protein points over three times are32.Through comparative proteome analysis of decidua tissues of model group,normal group,low-dose Shoutaiwan group,middle-dose Shoutaiwan group and low-dose Shoutaiwan group,30differential expression protein spots which maybe related to recurrent abortion and Shoutaiwan intervention were identified by MS.These differential expression proteins mainly refer to invasion of the blastocyst, blood vessel remodeling and cell apoptosis.
3.Validating of differential expression proteins pots of HSP27, α-enolase,Transferrin and Annexin A2:Used the methods of Western blot and immunohistochemical,HSP27and α-enolase expression in model group are significantly higher than the normal pregnancy group(P< 0.01);Transferrin and Annexin A2expression,ara significantly lower than the normal pregnancy group at decidua tissues (P<0.01);Compared with model group,Shoutaiwan low middle high-dose group can decreased significantly HSP27and α-enolase expression in decidua tissues of pregnant mice(P<0.01);Shoutaiwan low middle high-dose group make Annexin A2expression in decidua tissues increased significantly(P<0.01);Compared with model group,Shoutaiwan high-dose group can increased significantly Transferrin in decidua tissues(P<0.01),Shoutaiwan middle low-dose group show no significant difference(P>0.05).These was consistent with our proteome analysis results.
Conclusion:
1.Shoutaiwan can decrease recurrent abortion mice absorption rate of the embryos significantly,and play a role in preventing miscarriage.
2.The2-DE reference maps of decidua tissues of mice including model group,normal group,low-dose Shoutaiwan group,middle-dose Shoutaiwan group and low-dose Shoutaiwan group were established successfully.30differential expression proteins pots were identified.It indicated that recurrent abortion is a complicated process refer to diverse proteins participate and the comparison proteome analysis was a reliable method to sieve related proteins pots for recurrent abortion pathological changes.For several proteins pots expression of decidua tissues in recurrent abortion mice was regulated by Shoutaiwan,it provides contribution to the effect characteristic of multitarget.
3.The expression of HSP27, α-enolase,Transferrin and Annexin A2in Protein levels with the methods of immunohistochemical and Western blot analysis was consistented with our proteome analysis results.Thus identificated the stability and reliable of proteome analysis.Shoutaiwan could down-regulate the expression of HSP27, α-enolase and up-regulate the expression of Transferrin,Annexin A2in protein levels,which may be one of the mechanisms of Shoutaiwans preventing miscarriage effect.
引文
[1]梁小妍,刘学庆,丁裕斌,陈雪梅,王应雄,何俊琳.难免流产蜕膜组织遗传印记基因PEG10的表达[J].遗传.2008,30(6)：735-740
[2]陈巧儿,秦卫兵,叶嘉玲,杨宁,王一峰,刘玉兰,许玉芳.丙种球蛋白被动免疫治疗原因不明性反复自然流产研究[J].中国妇幼保健.2007,22(23)：3260-3262
[3]赵鸿汉,赵伟,田辉.寿胎丸治愈习惯性流产而顺产男女婴儿20例的分析.光明中医,2010,25(9)：1606-1607
[4]李艳玲.寿胎丸合举元煎治疗胎漏胎动不安60例[J].现代中医药.2008,28(2)：34-35
[5]刁莉.寿胎丸加减治疗胎漏胎动不安50例临床观察[J].临床名床医学.2004,24(6)：228
[6]范士秀.寿胎丸加减治疗习惯性流产12例[J].内蒙古中医药,2003,22(2)：2
[7]李宝华.寿胎丸加味治疗胎漏、胎动不安、堕胎、小产的体会[J].职业与健康,2005,21(1)：113
[8]潘星宇.寿胎丸加味治疗习惯性流产62例疗效观察[J].光明中医.2004,19(4)：59-60
[9]赵瑞兰.寿胎丸加味治疗自然流产84例临床观察[J].中国实用医药,2007,(4)：10
[10]钱正伟.寿胎丸加味治疗习惯性流产76例[J].浙江中医杂志,2009,44(9)：677
[11]苗凌娜.寿胎丸加味治疗习惯性流产35例[J].四川中医,2011,29(7)：93-94
[12]范丽丽.寿胎丸加味治疗习惯性流产临床观察[J].中医学报,2010,25(148)：535-536
[13]丘春东,孔晓玲.寿胎丸治疗免疫因素所致复发性流产68例的临床观察[J].中国医药指南,2011,9(19)：309
[14]谢玲,王玉.寿胎丸加味治疗先兆流产和习惯性流产43例.江西中医药,2011,42(342)：51
[15]郜洁,罗颂平.寿胎丸对肾虚-黄体抑制流产模型大鼠雌激素水平的影响.现代药物与临床,2011,26(4)：287-289
[16]郜洁,罗颂平,赵颖.寿胎丸对肾虚-黄体抑制大鼠流产模型黄体功能的影响.中药材,2011,34(7)：1113-1116
[17]赖毛华,尤昭玲,刘慧萍,等.寿胎丸对自然流产小鼠母胎界面SOCS3基因表达影响[J].中国中医药科技,2008,15(6)：457-459
[18]尤昭玲,赖毛华,何冬梅,等.寿胎丸对反复自然流产小鼠SOCS1基因表达和妊娠结局的影响[J].中国中医药科技,2008,15(6)：455-457
[19]刘慧萍,尤昭玲,雷磊,等.寿胎丸对自然流产模型小鼠母胎界面TNF-α mRNA和IL-4mRNA表达的影响[J].中医药导报,2008,14(10)：28
[20]尤昭玲,刘慧萍,雷磊,等.寿胎丸对小鼠自然流产模型蜕膜组织SOCS3蛋白表达影响[J].中医药导报,2008,14(9)：1
[21]刘慧萍,尤昭玲,卢芳国,等.寿胎丸对小鼠自然流产模型蜕膜组织SOCS1蛋白表达影响[J].中医药导报,2008,14(8)：6-8
[22]刘慧萍,尤昭玲,卢芳国,等.寿胎丸对自然流产模型小鼠母胎界面γ-干扰素和白介素-10基因表达的影响[J].中华中医药学刊,2009,27(7)：1447-1449
[23]尤昭玲,刘丹卓,赵新广,等.寿胎丸对CHL细胞株染色体畸变影响的研究[J].湖南中医药大学学报,2008,28(3)：6-8
[24]刘丹卓,尤昭玲,赵新广,等.寿胎丸对TA系菌株基因回变菌落影响的研究[J].湖 南中医药大学学报,2008,28(3)：9-11
[25]赵新广,尤昭玲,刘丹卓,等.寿胎丸对KM小鼠PCE/NCE比值及MNPCE率的影响[J].湖南中医药大学学报,2008,28(3)：12-14
[26]刘丹卓,尤昭玲,赵新广.寿胎丸对SD孕鼠胚胎-胎仔发育毒性的研究[J].时珍国医国药,2009,20(12)：2919-2920
[27]赵新广,尤昭玲,刘丹卓,等.寿胎丸对大耳白孕兔生殖功能及其胚胎发育毒性的研究[J].辽宁中医杂志,2009,36(12)：2185-2187
[28]Tyers M,Mann M.From genomics to proteomics[J].Nature,2003,422(6928):193-197
[29]Shankar R,Gude N,Cullinane F,et al.An emerging role for compreh-ensive proteome analysis in human pregnancy research[J].Reproduction,2005,129(6):685-696
[30]Shankar R,Cullinane F,Brennecke SP.Applications of proteomic methodologies to human pregnancy research:a growing gestation approaching delivery[J].Proteomics, 2004,4(7):1909-1917
[31]Zhang R,Barker L,Pinchev D.Mining biomarkers in human sera using proteomic tools[J].Proteomics,2004,4(1):244-256
[32]Hess AP,Hamilton AE,Talbi S.Decidual stromal cell response to paracrine signals from the trophoblast:amplification of immune and angiogenic modulators[J].Biol Reprod,2007,76(1):102-117
[33]乔海,王清明,陈惠鹏.波形蛋白在细胞凋亡中的变化[J].军事医学科学院院刊,2005,29(3)：275-277.
[34]Hughes JA,Coke-Yarborough CM,Chadwick NC,etal.High-molecular-weight tropomyosins localize to the contractile rings of dividing CNS cells but are absent from malignant pediatric and adult CNS tumors[J].Glia,2003,42(1):25-35
[35]Raval GN,Bhardwag S,Levine EA,etal.Loss of expression of tropomyosin-1,a novel classⅡ tumor suppressor that induces anoikis, in primary breast tumors[J]. Olwogene,2003,22(40):6194-6203
[36]Jiang DF,Ying WT,Lu YL,etal.Identification of metastasis-associated proteins by proteomic analysis and functional exploration of interleukin-18 in metastasis[J]. Proteomics,2003,3:724-737
[37]徐菲菲,刘秀华.钙网蛋白的生理及病理生理学作用[J].生理科学进展,2006,37(3)：216-220
[38]Liu Xiuhua.Calreticulin and cardiovascular diseases[J].International Journal of Pathology and Clinical Medicine,2006,26(5):440-443
[39]Hung CC,Ichimura T,Stevens JL,etal.Protection of renal epithelial cells against oxidative injury by endoplasmie reticulum stress preconditioning is mediated by ERK1/2 aetivation[J].J Biol Chem,2003,273:29317-29326
[40]Xiao F,Wei Y,Yang L,etal.A gene therapy for cancer based on the angiogenesis inhibitor,vasostatin[J].Gene Ther,2002,9(18):1207-1213
[41]Yao L,Pike SE,Pittaluga S,etal.Anti-tumor activities of the angiogenesis inhibitors interferon-inducible protein-10 and the calreticulin fragment vasostatin[J]. Cancer Immunol Immunother,2002,51 (7):358-366
[42]Zhao KJ,Cheng H,Zhu KJ,etal.Recombined DNA vaccines encoding calreticulin linked to HPV6bE7 enhance immune response and inhibit angiogenic activity in B16 melanoma mouse model expressing HPV 6bE7 antigen[J].Arch Dermatol Res,2006, 298(2):64-72
[43]张敏,曹云山,朱任之.膜联蛋白A1与肿瘤[J].国外医学·生理、病理科学与临床分册,2005,25(2)：139-142
[44]Gerke V,Moss S.Annexins:from structure to function[J]. PhysioRev,2002,82(10): 331-371
[45]Parente L,Solito E.Annexin 1:more than an antiphospholipase protein[J].Inflamm Res,2004,53(2):125-132
[46]Oh P,Li Y,Yu J,etal.Subtractive proteomic mapping of the endothelial surface in lung and solid tumours for tissue-specific therapy[J].Nature,2004,429(6992):629-635
[47]Bai XF,Ni XG,Zhao P,etal.Over expresion of annexin 1 in pancreatic cancer and its clinical significance[J].World J Gastroenterol,2004,10(10):1466-1470
[48]Kang JS,Calvo BF,Maygarden SJ,etal.Dysregulation of annexin I protein expression in high-grade prostatic intraepithelial neoplasia and prostate cancer[J].Clin Cancer Res,2002,8(1):117-123
[49]李淑红,岳亚飞,赵小鸽,等Human Annexin V在不同胎盘中的表达的定量分析[J].中国优生与遗传杂志,2005,13(10)：31-33
[50]Lumb RA,Bulleid NJ.Is protein disulfide isomerase a redox-dependent molecular chaperone[J]. The EMBO Journal,2002,21 (24):6763-6770
[51]Bucciantini M,Giannoni E,Chiti F,etal.Inherent toxicity of aggregates implies a common mechanism for protein misfolding diseases[J].Nature,2002,416:507-511
[52]Carris M,Villaverde A.Role of molecular chaperone in inclusion body formation[J].FEBS lett,2003,537(1):215-221
[53]周海平,贾翠娟,张渝英.蛋白质二硫键异构酶相关蛋白A的表达及性质的研究[J].生物工程学报,2004,20(4)：595-600
[54]Robert J.Evolution of heat shock protein and immunity [J].Dev ComP Immunol, 2003,27(6-7):449-464
[55]Katsuki K,Fujimoto M,zhang XY, etal.Feeding induces expression of heat shock proteins that reduce oxidative stress[J].FEBS Lett,2004,571 (1-3):187-191
[56]Baek SH,Min JN,Park EM,etal.Role of small heat shock protein HSP25 in radioresistance and glutathione-redox cycle[J].J cell Physiol,2000,183(1):100-107
[57]Mosser DD,Morinoto RI.Molecular chaperones and the stress of oncogenesis[J]. Oncogene,2004,23(16):2907-2918
[58]石春燕,孙丽洲,德伟,等.子痫前期患者胎盘组织氧化应激与Peroxiredoxin Ⅱ[J].现代妇产科进展,2008,17(12)：929-931
[59]Dodge ME,Wang J,Guy C,etal.Stress-induced heat shock protein 27 expression and its role in dorsal root ganglion neuronal survival[J].Brain Res,2006,1068(1):34-48
[60]林川,焦敏.子痫前期患者胎盘组织中HSP-27的表达变化及意义[J].山东医药,2011,51(30)：31-32
[61]朱理安,方宁远.α-烯醇化酶——古老的蛋白,崭新的功能[J].国际病理科学与临床杂志,2007,27(4)：347-350
[62]Mizukami Y,Iwamatsu A,Aki T,etal.ERK1/2 regulates intracellularar ATP levels through α-enolase expression in cardiomyocytes exposed to ischemic hypoxia and reoxygenation[J]J Bio Chem,2004,279 (48):50120-50131
[63]Xian J,Li X,Li-shun W,etal.Differential protein expression in hypertrophio haart with and without hypertention in spontaneously hypertansiverats[J].Proteomicx,2006, 6(3):1948-1956
[64]Poon H F,Vaishnav R A,Getchell T V,etal.Quantitative proteomics analysis of differental protein expression and oxidative modification of specific proteins in the brains of old mice [J]Neurobiol Aging,2006,27(7):1010-1019
[65]张磊,门可,张景霞,等.人正常早孕滋养细胞体外培养株的系统鉴定[J].中国公共卫生,2006,22(7)：818-820
[66]Heaton SJ,Eady JJ,Parker ML,etal.The use of Be Wo cells as an invitromodel forplacental iron transport[J]. Am J Physiol Cell Physiol,2008,295(5):C1445-1453
[67]Li YQ,Yan H,Bai B.Change in iron transporter expression in human term placenta with different maternal iron status[J].Eur J Obstet Gynecol Reprod Biol,2008,140(1): 48-54
[68]Li H,Sun H,Qian ZM.The role of the transferrin-transferrin-receptor system in drug delivery and targeting[J].Trends Pharmacol Sci,2002,23(5):206-209
[69]Zhong W,Parkinson JA,Guo M,etal.Unusual features for zirconium(Ⅳ) binding to human serum transferrin[J] J Biol Inorg Chem,2002,7(6):589-599
[70]Bastin J,Drakesmith H,Rees M,Sargent I,Townsend A.Localisation of proteins of iron metabolism in the human placenta and liver [J].Br J Haematol,2006,134(5):532-543
[71]Gerke V,Moss S. Annex ins:from structure to function[J].PhysioRev.2002,82(10): 331-371
[72]张立勇,赵晓航,吴昊.膜联蛋白Ⅰ的结构和功能[J].生物化学与生物物理进展,2002,29(4)：514-517
[73]Filipenko NR,visman DM.Annexins:Biological importance and Annexin-related Pathologies[J].Landes Bioscience, Georgetown, TX,2003,127-156
[74]Benaud C,Gentil BJ,Assard N,etal.AHNAK interaction with the annexin 2/5100A10 eomplex regulates cell membrane cytoarchitecture[J].J Cell Biol,2004, 164(1):133-144
[75]Li F,Chung H,Reddy SV,etal.Annexin Ⅱ stimulates RANKL expression through MAPK[J].J Bone Miner Res,2005,20(7):1161-1167
[76]Gilmore WS,Olwill S,McGlynn H, etal.Annexin A2 expression during cellular differentiation in myeloid cell lines[J].Biochemical Society Transactions,2004,32(6): 1122-1123
[77]Van de Graaf SF,Hoenderop JG,Gkika D,etal.Functional expression of the epithelial Ca(2+)channels (TRPV5 and TRPV6)requires association of the S100A10-annexin2 complex[J].EMBO J,2003,22(7):1478-1487
[78]Ling Q,Jacovina AT,Deora A,etal.Annexin Ⅱ regulates fibrin homeostasis and neoangiogenesis in vivo[J].J Clin Invest,2004,113:38-48
[79]Tanaka Y,Ishii H,Hiraoka M,etal.Efficacy of recombinant annexin-2 for fibrinolytic therapy in a rat embolic stroke model:a magnetic resonance imaging study[J].Brain Rcs,2007,1165:135-143
[1]钱正伟.寿胎丸加味治疗习惯性流产76例[J].浙江中医杂志,2009,44(9)：677
[2]苗凌娜.寿胎丸加味治疗习惯性流产35例[J].四川中医,2011,29(7)：93-94
[3]范丽丽.寿胎丸加味治疗习惯性流产临床观察[J].中医学报,2010,25(148)：535-536
[4]邱春东,孔晓玲.寿胎丸治疗免疫因素所致复发性流产68例的临床观察[J].中国医药指南,2011,9(19)：309
[5]郜洁,罗颂平.寿胎丸对肾虚-黄体抑制流产模型大鼠雌激素水平的影响.现代药物与临床,2011,26(4)：287-289
[6]郜洁,罗颂平,赵颖.寿胎丸对肾虚-黄体抑制大鼠流产模型黄体功能的影响.中药材,2011,34(7)：1113-1116
[7]赖毛华,尤昭玲,刘慧萍,等.寿胎丸对自然流产小鼠母胎界面SOCS3基因表达影响[J].中国中医药科技,2008,15(6)：457-459
[8]尤昭玲,赖毛华,何冬梅,等.寿胎丸对反复自然流产小鼠SOCS1基因表达和妊娠结局的影响[J].中国中医药科技,2008,15(6)：455-457
[9]刘慧萍,尤昭玲,雷磊,等.寿胎丸对自然流产模型小鼠母胎界面TNF-αmRNA和IL-4mRNA表达的影响[J].中医药导报,2008,14(10)：28
[10]尤昭玲,刘慧萍,雷磊,等.寿胎丸对小鼠自然流产模型蜕膜组织SOCS3蛋白表达影响[J].中医药导报,2008,14(9)：1
[11]刘慧萍,尤昭玲,卢芳国,等.寿胎丸对小鼠自然流产模型蜕膜组织SOCS1蛋白表达影响[J].中医药导报,2008,14(8)：6-8
[12]刘慧萍,尤昭玲,卢芳国,等.寿胎丸对自然流产模型小鼠母胎界面Y-干扰素和白介素-10基因表达的影响[J].中华中医药学刊,2009,27(7)：1447-1449
[13]尤昭玲,刘丹卓,赵新广,等.寿胎丸对CHL细胞株染色体畸变影响的研究[J].湖南中医药大学学报,2008,28(3)：6-8
[14]刘丹卓,尤昭玲,赵新广,等.寿胎丸对TA系菌株基因回变菌落影响的研究[J].湖南中医药大学学报,2008,28(3)：9-11
[15]赵新广,尤昭玲,刘丹卓,等.寿胎丸对KM小鼠PCE/NCE比值及MNPCE率的影响[J].湖南中医药大学学报,2008,28(3)：12-14
[16]刘丹卓,尤昭玲,赵新广.寿胎丸对SD孕鼠胚胎-胎仔发育毒性的研究[J].时珍国医国药,2009,20(12)：2919-2920
[17]赵新广,尤昭玲,刘丹卓,等.寿胎丸对大耳白孕兔生殖功能及其胚胎发育毒性的研究[J].辽宁中医杂,志,2009,36(12)：2185-2187
[18]李建平,王静,张跃文,等.菟丝子的研究进展[J].中国医药导报,2009,6(23)：5-6
[19]马红霞,尤昭玲,王若光,等.菟丝子总黄酮对大鼠流产模型妊娠结局及胎盘、蜕膜形态学的影响[J].中药材,2008,31(7)：1044-1046
[20]马红霞,尤昭玲,王若光.菟丝子总黄酮对大鼠流产模型血清P、PR、Th1/Th2细胞因子表达的影响[J].中药材,2008,31(8)：1201-1204
[21]马红霞,尤昭玲,王小云.菟丝子总黄酮对大鼠流产模型母-胎界面Fas/FasL、 PCNA、HB-EGF表达的影响[J].中药材,2008,31(11)：1706-1709
[22]刘华,韦炳华,马红霞,等.菟丝子黄酮对流产大鼠模型母胎免疫平衡因子的影响[J].世界中西医结合杂志,2011,6(10)：837-841
[23]陈林林,吴春,李伟.菟丝子黄酮的抗氧化性能研究[J].食品工业科技,2008,29(11)：116-121
[24]兰鸿,杜士明.菟丝子提取物对自然衰老小鼠的抗衰老作用研究[J].中国药房2010,21(39)：3667-3669
[25]潘文灏,许志超,赵余庆.菟丝子的生物活性与临床应用研究进展[J].亚太传统医药,2008,4(4)：47-51
[26]孙、雪莹,洪敏,朱荃.雌二醇对活化脾细胞增殖的抑制作用及桑寄生的干预[J].中药药理与临床,2005,21(6)：44-46
[27]张秀敏,刘冉,许津.中药桑寄生的抗Ⅰ型变态反应作用[J].中国药师,2005,8(1)：5-7
[28]何国萍.续断的药理作用与临床应用[J].中国药物滥用防治杂志,2010,16(2)：120-122
[29]张艳青,张春凤,杨中林.不同粒度续断饮片中续断皂苷溶出速率及其雌激素样作用研究[J].医药导报,2009,28(11)：1402-1404
[30]黄丽亚,叶嗣颖.延龄草续断上调抗氧化酶表达作用的比较研究[J].辽宁中医杂志,2006,33(8)：1012-1013
[31]邓皖利,吴宏忠,徐文,等.阿胶补血活性组分对环磷酰胺所致贫血小鼠骨髓造血微环境的影响[J].时珍国医国药,201 1,22(10)：2542-2544
[32]吴宏忠,杨帆,崔书亚,等.阿胶酶解成分对贫血小鼠造血系统的保护机制[J].华东理工大学学报,2008,34(1)：47-52
[33]张殉,王静凤,李冰,等.阿胶对小鼠免疫功能的影响[J].食品工业科技,2011,32(11)：400-402
[34]何冬梅,雷磊,尤昭玲.寿胎丸治疗习惯性流产研究进展[J].中医药导报,2008,14(12)：81-83
[35]Kruse U,Bantscheff M,Drewes G,etal.Chemical and pathway proteomics: powerful tools for oncology drug discovery and personalized health care[J]. Mol Cell Proteomics,2008,7(10):1887-1901
[36]Deutsch EW,Lam H,Aebersold R.Data analysis and bioinformatics tools for tandem mass spectrometry in proteomics[J].Physiol Genomics,2008,33(1):18-25
[37]李治国,肖诚,李平.蛋白质组学是中医药现代化研究的重要工具[J].世界科学技术-中医药现代化,2007,9(3)：81-85
[38]赵慧辉,王伟,郭淑贞.冠心病不稳定型心绞痛血瘀证的蛋白质组学[J].中国动脉硬化杂志,2008,16(7)：545-548
[39]孙晓敏,谭为,罗仁,等.慢性肾小球肾炎肾阴虚证血浆蛋白质双向凝胶电泳分析[J].热带医学杂志,2011,11(4)：433-435
[40]战丽彬,刘莉,路小光,等.脾阴虚证大鼠海马蛋白质组双向凝胶电泳的研究[J].中华中医药杂志,2009,24(2)：149-152
[41]褚瑜光,石洁,胡元会,等.高血压病中医肝胆湿热证患者血清蛋白质组学研究[J].中国中西医结合杂志,2010,30(1)：37-41
[42]崔佩佩,朱明丹,姜民,等.痰浊内阻及心气虚弱型冠心病患者的比较蛋白质组学研究[J].中医杂志,2011,52(增刊)：75-77
[43]刘涛,徐秋玲,王伟,等.气虚血瘀证大鼠模型缺血心肌蛋白质组学研究[J].江苏中医药,2010,42(7)：67-69
[44]Ma ZC, Tan HL, Xiao CR,etal. Proteomic analysis of the effects of tetramethylpyrazine on irradiated QXMSC1 cells[J].BiolPharm Bull.2007,Feb,30(2): 397-402
[45]张珍,闵玮,林秉奖,等.黄芩苷对HaCaT细胞影响的蛋白组学研究[J].中国中西医结合皮肤性病学杂志,2011,10(2)：83-86
[46]卢德赵,林韬琦,沃兴德,等.RAW264.7细胞中姜黄素抗动脉粥样硬化作用机制的蛋白质组学研究[J].中国中药杂志,2011,36(9)：1207-1211
[47]赵春珍,张春来,徐倩,等.人参皂甙Rb1对马桑内酯癫痫的作用及海马蛋白组表达的影响[J].泸州医学院学报,2011,34(5)：539-545
[48]曾建春,樊粤光,刘建仁,等.杜仲含药血清诱导骨髓间充质干细胞定向分化蛋白质组学研究[J].时珍国医国药,2010,21(2)：274-277
[49]苗兰,潘映红,任建勋,等.血府逐瘀汤对气滞血瘀证大鼠血清蛋白质组表达的影响[J].中国实验方剂学杂志,2008,14(4)：24-28
[50]张婷,董克礼,李广诚.益智健脑颗粒水提浓缩液对P8系快速老化小鼠内嗅区组织差异蛋白质表达的影响[J].中国中西医结合杂志,2010,30(5)：504-508
[51]黄黎明,石晓强,梁恒.黄芪、山茱萸对肾炎小鼠尿蛋白谱的影响[J].中国中药杂志,2007,32(13)：1324-1328
[52]刘焕兰,陈炜,曲卫玲,等.应用蛋白质组学技术研究琼玉膏抗衰老的作用机制[J].现代中西医结合杂志,2010,19(29)：3814-3815
[53]龚文君,沃兴德,卢德赵,等.四物汤对血虚证模型大鼠肝线粒体蛋白质组的影响[J].中医杂志,2010,51(2)：160-163
[54]严冬梅,李敏军,刘秋君.四君子汤及党参对小鼠神经细胞蛋白质组表达的影响[J].时珍国医国药,2011,22(3)：602-603
[55]陈倩,谭彬,王应雄,等.自然流产患者蜕膜组织疾病特异蛋白的初步筛选与鉴定[J].重庆医学,2010,39(21)：2861-2863
[2]陈巧儿,秦卫兵,叶嘉玲,杨宁,王一峰,刘玉兰,许玉芳.丙种球蛋白被动免疫治疗原因不明性反复自然流产研究[J].中国妇幼保健.2007,22(23)：3260-3262
[3]赵鸿汉,赵伟,田辉.寿胎丸治愈习惯性流产而顺产男女婴儿20例的分析.光明中医,2010,25(9)：1606-1607
[4]李艳玲.寿胎丸合举元煎治疗胎漏胎动不安60例[J].现代中医药.2008,28(2)：34-35
[5]刁莉.寿胎丸加减治疗胎漏胎动不安50例临床观察[J].临床名床医学.2004,24(6)：228
[6]范士秀.寿胎丸加减治疗习惯性流产12例[J].内蒙古中医药,2003,22(2)：2
[7]李宝华.寿胎丸加味治疗胎漏、胎动不安、堕胎、小产的体会[J].职业与健康,2005,21(1)：113
[8]潘星宇.寿胎丸加味治疗习惯性流产62例疗效观察[J].光明中医.2004,19(4)：59-60
[9]赵瑞兰.寿胎丸加味治疗自然流产84例临床观察[J].中国实用医药,2007,(4)：10
[10]钱正伟.寿胎丸加味治疗习惯性流产76例[J].浙江中医杂志,2009,44(9)：677
[11]苗凌娜.寿胎丸加味治疗习惯性流产35例[J].四川中医,2011,29(7)：93-94
[12]范丽丽.寿胎丸加味治疗习惯性流产临床观察[J].中医学报,2010,25(148)：535-536
[13]丘春东,孔晓玲.寿胎丸治疗免疫因素所致复发性流产68例的临床观察[J].中国医药指南,2011,9(19)：309
[14]谢玲,王玉.寿胎丸加味治疗先兆流产和习惯性流产43例.江西中医药,2011,42(342)：51
[15]郜洁,罗颂平.寿胎丸对肾虚-黄体抑制流产模型大鼠雌激素水平的影响.现代药物与临床,2011,26(4)：287-289
[16]郜洁,罗颂平,赵颖.寿胎丸对肾虚-黄体抑制大鼠流产模型黄体功能的影响.中药材,2011,34(7)：1113-1116
[17]赖毛华,尤昭玲,刘慧萍,等.寿胎丸对自然流产小鼠母胎界面SOCS3基因表达影响[J].中国中医药科技,2008,15(6)：457-459
[18]尤昭玲,赖毛华,何冬梅,等.寿胎丸对反复自然流产小鼠SOCS1基因表达和妊娠结局的影响[J].中国中医药科技,2008,15(6)：455-457
[19]刘慧萍,尤昭玲,雷磊,等.寿胎丸对自然流产模型小鼠母胎界面TNF-α mRNA和IL-4mRNA表达的影响[J].中医药导报,2008,14(10)：28
[20]尤昭玲,刘慧萍,雷磊,等.寿胎丸对小鼠自然流产模型蜕膜组织SOCS3蛋白表达影响[J].中医药导报,2008,14(9)：1
[21]刘慧萍,尤昭玲,卢芳国,等.寿胎丸对小鼠自然流产模型蜕膜组织SOCS1蛋白表达影响[J].中医药导报,2008,14(8)：6-8
[22]刘慧萍,尤昭玲,卢芳国,等.寿胎丸对自然流产模型小鼠母胎界面γ-干扰素和白介素-10基因表达的影响[J].中华中医药学刊,2009,27(7)：1447-1449
[23]尤昭玲,刘丹卓,赵新广,等.寿胎丸对CHL细胞株染色体畸变影响的研究[J].湖南中医药大学学报,2008,28(3)：6-8
[24]刘丹卓,尤昭玲,赵新广,等.寿胎丸对TA系菌株基因回变菌落影响的研究[J].湖 南中医药大学学报,2008,28(3)：9-11
[25]赵新广,尤昭玲,刘丹卓,等.寿胎丸对KM小鼠PCE/NCE比值及MNPCE率的影响[J].湖南中医药大学学报,2008,28(3)：12-14
[26]刘丹卓,尤昭玲,赵新广.寿胎丸对SD孕鼠胚胎-胎仔发育毒性的研究[J].时珍国医国药,2009,20(12)：2919-2920
[27]赵新广,尤昭玲,刘丹卓,等.寿胎丸对大耳白孕兔生殖功能及其胚胎发育毒性的研究[J].辽宁中医杂志,2009,36(12)：2185-2187
[28]Tyers M,Mann M.From genomics to proteomics[J].Nature,2003,422(6928):193-197
[29]Shankar R,Gude N,Cullinane F,et al.An emerging role for compreh-ensive proteome analysis in human pregnancy research[J].Reproduction,2005,129(6):685-696
[30]Shankar R,Cullinane F,Brennecke SP.Applications of proteomic methodologies to human pregnancy research:a growing gestation approaching delivery[J].Proteomics, 2004,4(7):1909-1917
[31]Zhang R,Barker L,Pinchev D.Mining biomarkers in human sera using proteomic tools[J].Proteomics,2004,4(1):244-256
[32]Hess AP,Hamilton AE,Talbi S.Decidual stromal cell response to paracrine signals from the trophoblast:amplification of immune and angiogenic modulators[J].Biol Reprod,2007,76(1):102-117
[33]乔海,王清明,陈惠鹏.波形蛋白在细胞凋亡中的变化[J].军事医学科学院院刊,2005,29(3)：275-277.
[34]Hughes JA,Coke-Yarborough CM,Chadwick NC,etal.High-molecular-weight tropomyosins localize to the contractile rings of dividing CNS cells but are absent from malignant pediatric and adult CNS tumors[J].Glia,2003,42(1):25-35
[35]Raval GN,Bhardwag S,Levine EA,etal.Loss of expression of tropomyosin-1,a novel classⅡ tumor suppressor that induces anoikis, in primary breast tumors[J]. Olwogene,2003,22(40):6194-6203
[36]Jiang DF,Ying WT,Lu YL,etal.Identification of metastasis-associated proteins by proteomic analysis and functional exploration of interleukin-18 in metastasis[J]. Proteomics,2003,3:724-737
[37]徐菲菲,刘秀华.钙网蛋白的生理及病理生理学作用[J].生理科学进展,2006,37(3)：216-220
[38]Liu Xiuhua.Calreticulin and cardiovascular diseases[J].International Journal of Pathology and Clinical Medicine,2006,26(5):440-443
[39]Hung CC,Ichimura T,Stevens JL,etal.Protection of renal epithelial cells against oxidative injury by endoplasmie reticulum stress preconditioning is mediated by ERK1/2 aetivation[J].J Biol Chem,2003,273:29317-29326
[40]Xiao F,Wei Y,Yang L,etal.A gene therapy for cancer based on the angiogenesis inhibitor,vasostatin[J].Gene Ther,2002,9(18):1207-1213
[41]Yao L,Pike SE,Pittaluga S,etal.Anti-tumor activities of the angiogenesis inhibitors interferon-inducible protein-10 and the calreticulin fragment vasostatin[J]. Cancer Immunol Immunother,2002,51 (7):358-366
[42]Zhao KJ,Cheng H,Zhu KJ,etal.Recombined DNA vaccines encoding calreticulin linked to HPV6bE7 enhance immune response and inhibit angiogenic activity in B16 melanoma mouse model expressing HPV 6bE7 antigen[J].Arch Dermatol Res,2006, 298(2):64-72
[43]张敏,曹云山,朱任之.膜联蛋白A1与肿瘤[J].国外医学·生理、病理科学与临床分册,2005,25(2)：139-142
[44]Gerke V,Moss S.Annexins:from structure to function[J]. PhysioRev,2002,82(10): 331-371
[45]Parente L,Solito E.Annexin 1:more than an antiphospholipase protein[J].Inflamm Res,2004,53(2):125-132
[46]Oh P,Li Y,Yu J,etal.Subtractive proteomic mapping of the endothelial surface in lung and solid tumours for tissue-specific therapy[J].Nature,2004,429(6992):629-635
[47]Bai XF,Ni XG,Zhao P,etal.Over expresion of annexin 1 in pancreatic cancer and its clinical significance[J].World J Gastroenterol,2004,10(10):1466-1470
[48]Kang JS,Calvo BF,Maygarden SJ,etal.Dysregulation of annexin I protein expression in high-grade prostatic intraepithelial neoplasia and prostate cancer[J].Clin Cancer Res,2002,8(1):117-123
[49]李淑红,岳亚飞,赵小鸽,等Human Annexin V在不同胎盘中的表达的定量分析[J].中国优生与遗传杂志,2005,13(10)：31-33
[50]Lumb RA,Bulleid NJ.Is protein disulfide isomerase a redox-dependent molecular chaperone[J]. The EMBO Journal,2002,21 (24):6763-6770
[51]Bucciantini M,Giannoni E,Chiti F,etal.Inherent toxicity of aggregates implies a common mechanism for protein misfolding diseases[J].Nature,2002,416:507-511
[52]Carris M,Villaverde A.Role of molecular chaperone in inclusion body formation[J].FEBS lett,2003,537(1):215-221
[53]周海平,贾翠娟,张渝英.蛋白质二硫键异构酶相关蛋白A的表达及性质的研究[J].生物工程学报,2004,20(4)：595-600
[54]Robert J.Evolution of heat shock protein and immunity [J].Dev ComP Immunol, 2003,27(6-7):449-464
[55]Katsuki K,Fujimoto M,zhang XY, etal.Feeding induces expression of heat shock proteins that reduce oxidative stress[J].FEBS Lett,2004,571 (1-3):187-191
[56]Baek SH,Min JN,Park EM,etal.Role of small heat shock protein HSP25 in radioresistance and glutathione-redox cycle[J].J cell Physiol,2000,183(1):100-107
[57]Mosser DD,Morinoto RI.Molecular chaperones and the stress of oncogenesis[J]. Oncogene,2004,23(16):2907-2918
[58]石春燕,孙丽洲,德伟,等.子痫前期患者胎盘组织氧化应激与Peroxiredoxin Ⅱ[J].现代妇产科进展,2008,17(12)：929-931
[59]Dodge ME,Wang J,Guy C,etal.Stress-induced heat shock protein 27 expression and its role in dorsal root ganglion neuronal survival[J].Brain Res,2006,1068(1):34-48
[60]林川,焦敏.子痫前期患者胎盘组织中HSP-27的表达变化及意义[J].山东医药,2011,51(30)：31-32
[61]朱理安,方宁远.α-烯醇化酶——古老的蛋白,崭新的功能[J].国际病理科学与临床杂志,2007,27(4)：347-350
[62]Mizukami Y,Iwamatsu A,Aki T,etal.ERK1/2 regulates intracellularar ATP levels through α-enolase expression in cardiomyocytes exposed to ischemic hypoxia and reoxygenation[J]J Bio Chem,2004,279 (48):50120-50131
[63]Xian J,Li X,Li-shun W,etal.Differential protein expression in hypertrophio haart with and without hypertention in spontaneously hypertansiverats[J].Proteomicx,2006, 6(3):1948-1956
[64]Poon H F,Vaishnav R A,Getchell T V,etal.Quantitative proteomics analysis of differental protein expression and oxidative modification of specific proteins in the brains of old mice [J]Neurobiol Aging,2006,27(7):1010-1019
[65]张磊,门可,张景霞,等.人正常早孕滋养细胞体外培养株的系统鉴定[J].中国公共卫生,2006,22(7)：818-820
[66]Heaton SJ,Eady JJ,Parker ML,etal.The use of Be Wo cells as an invitromodel forplacental iron transport[J]. Am J Physiol Cell Physiol,2008,295(5):C1445-1453
[67]Li YQ,Yan H,Bai B.Change in iron transporter expression in human term placenta with different maternal iron status[J].Eur J Obstet Gynecol Reprod Biol,2008,140(1): 48-54
[68]Li H,Sun H,Qian ZM.The role of the transferrin-transferrin-receptor system in drug delivery and targeting[J].Trends Pharmacol Sci,2002,23(5):206-209
[69]Zhong W,Parkinson JA,Guo M,etal.Unusual features for zirconium(Ⅳ) binding to human serum transferrin[J] J Biol Inorg Chem,2002,7(6):589-599
[70]Bastin J,Drakesmith H,Rees M,Sargent I,Townsend A.Localisation of proteins of iron metabolism in the human placenta and liver [J].Br J Haematol,2006,134(5):532-543
[71]Gerke V,Moss S. Annex ins:from structure to function[J].PhysioRev.2002,82(10): 331-371
[72]张立勇,赵晓航,吴昊.膜联蛋白Ⅰ的结构和功能[J].生物化学与生物物理进展,2002,29(4)：514-517
[73]Filipenko NR,visman DM.Annexins:Biological importance and Annexin-related Pathologies[J].Landes Bioscience, Georgetown, TX,2003,127-156
[74]Benaud C,Gentil BJ,Assard N,etal.AHNAK interaction with the annexin 2/5100A10 eomplex regulates cell membrane cytoarchitecture[J].J Cell Biol,2004, 164(1):133-144
[75]Li F,Chung H,Reddy SV,etal.Annexin Ⅱ stimulates RANKL expression through MAPK[J].J Bone Miner Res,2005,20(7):1161-1167
[76]Gilmore WS,Olwill S,McGlynn H, etal.Annexin A2 expression during cellular differentiation in myeloid cell lines[J].Biochemical Society Transactions,2004,32(6): 1122-1123
[77]Van de Graaf SF,Hoenderop JG,Gkika D,etal.Functional expression of the epithelial Ca(2+)channels (TRPV5 and TRPV6)requires association of the S100A10-annexin2 complex[J].EMBO J,2003,22(7):1478-1487
[78]Ling Q,Jacovina AT,Deora A,etal.Annexin Ⅱ regulates fibrin homeostasis and neoangiogenesis in vivo[J].J Clin Invest,2004,113:38-48
[79]Tanaka Y,Ishii H,Hiraoka M,etal.Efficacy of recombinant annexin-2 for fibrinolytic therapy in a rat embolic stroke model:a magnetic resonance imaging study[J].Brain Rcs,2007,1165:135-143
[1]钱正伟.寿胎丸加味治疗习惯性流产76例[J].浙江中医杂志,2009,44(9)：677
[2]苗凌娜.寿胎丸加味治疗习惯性流产35例[J].四川中医,2011,29(7)：93-94
[3]范丽丽.寿胎丸加味治疗习惯性流产临床观察[J].中医学报,2010,25(148)：535-536
[4]邱春东,孔晓玲.寿胎丸治疗免疫因素所致复发性流产68例的临床观察[J].中国医药指南,2011,9(19)：309
[5]郜洁,罗颂平.寿胎丸对肾虚-黄体抑制流产模型大鼠雌激素水平的影响.现代药物与临床,2011,26(4)：287-289
[6]郜洁,罗颂平,赵颖.寿胎丸对肾虚-黄体抑制大鼠流产模型黄体功能的影响.中药材,2011,34(7)：1113-1116
[7]赖毛华,尤昭玲,刘慧萍,等.寿胎丸对自然流产小鼠母胎界面SOCS3基因表达影响[J].中国中医药科技,2008,15(6)：457-459
[8]尤昭玲,赖毛华,何冬梅,等.寿胎丸对反复自然流产小鼠SOCS1基因表达和妊娠结局的影响[J].中国中医药科技,2008,15(6)：455-457
[9]刘慧萍,尤昭玲,雷磊,等.寿胎丸对自然流产模型小鼠母胎界面TNF-αmRNA和IL-4mRNA表达的影响[J].中医药导报,2008,14(10)：28
[10]尤昭玲,刘慧萍,雷磊,等.寿胎丸对小鼠自然流产模型蜕膜组织SOCS3蛋白表达影响[J].中医药导报,2008,14(9)：1
[11]刘慧萍,尤昭玲,卢芳国,等.寿胎丸对小鼠自然流产模型蜕膜组织SOCS1蛋白表达影响[J].中医药导报,2008,14(8)：6-8
[12]刘慧萍,尤昭玲,卢芳国,等.寿胎丸对自然流产模型小鼠母胎界面Y-干扰素和白介素-10基因表达的影响[J].中华中医药学刊,2009,27(7)：1447-1449
[13]尤昭玲,刘丹卓,赵新广,等.寿胎丸对CHL细胞株染色体畸变影响的研究[J].湖南中医药大学学报,2008,28(3)：6-8
[14]刘丹卓,尤昭玲,赵新广,等.寿胎丸对TA系菌株基因回变菌落影响的研究[J].湖南中医药大学学报,2008,28(3)：9-11
[15]赵新广,尤昭玲,刘丹卓,等.寿胎丸对KM小鼠PCE/NCE比值及MNPCE率的影响[J].湖南中医药大学学报,2008,28(3)：12-14
[16]刘丹卓,尤昭玲,赵新广.寿胎丸对SD孕鼠胚胎-胎仔发育毒性的研究[J].时珍国医国药,2009,20(12)：2919-2920
[17]赵新广,尤昭玲,刘丹卓,等.寿胎丸对大耳白孕兔生殖功能及其胚胎发育毒性的研究[J].辽宁中医杂,志,2009,36(12)：2185-2187
[18]李建平,王静,张跃文,等.菟丝子的研究进展[J].中国医药导报,2009,6(23)：5-6
[19]马红霞,尤昭玲,王若光,等.菟丝子总黄酮对大鼠流产模型妊娠结局及胎盘、蜕膜形态学的影响[J].中药材,2008,31(7)：1044-1046
[20]马红霞,尤昭玲,王若光.菟丝子总黄酮对大鼠流产模型血清P、PR、Th1/Th2细胞因子表达的影响[J].中药材,2008,31(8)：1201-1204
[21]马红霞,尤昭玲,王小云.菟丝子总黄酮对大鼠流产模型母-胎界面Fas/FasL、 PCNA、HB-EGF表达的影响[J].中药材,2008,31(11)：1706-1709
[22]刘华,韦炳华,马红霞,等.菟丝子黄酮对流产大鼠模型母胎免疫平衡因子的影响[J].世界中西医结合杂志,2011,6(10)：837-841
[23]陈林林,吴春,李伟.菟丝子黄酮的抗氧化性能研究[J].食品工业科技,2008,29(11)：116-121
[24]兰鸿,杜士明.菟丝子提取物对自然衰老小鼠的抗衰老作用研究[J].中国药房2010,21(39)：3667-3669
[25]潘文灏,许志超,赵余庆.菟丝子的生物活性与临床应用研究进展[J].亚太传统医药,2008,4(4)：47-51
[26]孙、雪莹,洪敏,朱荃.雌二醇对活化脾细胞增殖的抑制作用及桑寄生的干预[J].中药药理与临床,2005,21(6)：44-46
[27]张秀敏,刘冉,许津.中药桑寄生的抗Ⅰ型变态反应作用[J].中国药师,2005,8(1)：5-7
[28]何国萍.续断的药理作用与临床应用[J].中国药物滥用防治杂志,2010,16(2)：120-122
[29]张艳青,张春凤,杨中林.不同粒度续断饮片中续断皂苷溶出速率及其雌激素样作用研究[J].医药导报,2009,28(11)：1402-1404
[30]黄丽亚,叶嗣颖.延龄草续断上调抗氧化酶表达作用的比较研究[J].辽宁中医杂志,2006,33(8)：1012-1013
[31]邓皖利,吴宏忠,徐文,等.阿胶补血活性组分对环磷酰胺所致贫血小鼠骨髓造血微环境的影响[J].时珍国医国药,201 1,22(10)：2542-2544
[32]吴宏忠,杨帆,崔书亚,等.阿胶酶解成分对贫血小鼠造血系统的保护机制[J].华东理工大学学报,2008,34(1)：47-52
[33]张殉,王静凤,李冰,等.阿胶对小鼠免疫功能的影响[J].食品工业科技,2011,32(11)：400-402
[34]何冬梅,雷磊,尤昭玲.寿胎丸治疗习惯性流产研究进展[J].中医药导报,2008,14(12)：81-83
[35]Kruse U,Bantscheff M,Drewes G,etal.Chemical and pathway proteomics: powerful tools for oncology drug discovery and personalized health care[J]. Mol Cell Proteomics,2008,7(10):1887-1901
[36]Deutsch EW,Lam H,Aebersold R.Data analysis and bioinformatics tools for tandem mass spectrometry in proteomics[J].Physiol Genomics,2008,33(1):18-25
[37]李治国,肖诚,李平.蛋白质组学是中医药现代化研究的重要工具[J].世界科学技术-中医药现代化,2007,9(3)：81-85
[38]赵慧辉,王伟,郭淑贞.冠心病不稳定型心绞痛血瘀证的蛋白质组学[J].中国动脉硬化杂志,2008,16(7)：545-548
[39]孙晓敏,谭为,罗仁,等.慢性肾小球肾炎肾阴虚证血浆蛋白质双向凝胶电泳分析[J].热带医学杂志,2011,11(4)：433-435
[40]战丽彬,刘莉,路小光,等.脾阴虚证大鼠海马蛋白质组双向凝胶电泳的研究[J].中华中医药杂志,2009,24(2)：149-152
[41]褚瑜光,石洁,胡元会,等.高血压病中医肝胆湿热证患者血清蛋白质组学研究[J].中国中西医结合杂志,2010,30(1)：37-41
[42]崔佩佩,朱明丹,姜民,等.痰浊内阻及心气虚弱型冠心病患者的比较蛋白质组学研究[J].中医杂志,2011,52(增刊)：75-77
[43]刘涛,徐秋玲,王伟,等.气虚血瘀证大鼠模型缺血心肌蛋白质组学研究[J].江苏中医药,2010,42(7)：67-69
[44]Ma ZC, Tan HL, Xiao CR,etal. Proteomic analysis of the effects of tetramethylpyrazine on irradiated QXMSC1 cells[J].BiolPharm Bull.2007,Feb,30(2): 397-402
[45]张珍,闵玮,林秉奖,等.黄芩苷对HaCaT细胞影响的蛋白组学研究[J].中国中西医结合皮肤性病学杂志,2011,10(2)：83-86
[46]卢德赵,林韬琦,沃兴德,等.RAW264.7细胞中姜黄素抗动脉粥样硬化作用机制的蛋白质组学研究[J].中国中药杂志,2011,36(9)：1207-1211
[47]赵春珍,张春来,徐倩,等.人参皂甙Rb1对马桑内酯癫痫的作用及海马蛋白组表达的影响[J].泸州医学院学报,2011,34(5)：539-545
[48]曾建春,樊粤光,刘建仁,等.杜仲含药血清诱导骨髓间充质干细胞定向分化蛋白质组学研究[J].时珍国医国药,2010,21(2)：274-277
[49]苗兰,潘映红,任建勋,等.血府逐瘀汤对气滞血瘀证大鼠血清蛋白质组表达的影响[J].中国实验方剂学杂志,2008,14(4)：24-28
[50]张婷,董克礼,李广诚.益智健脑颗粒水提浓缩液对P8系快速老化小鼠内嗅区组织差异蛋白质表达的影响[J].中国中西医结合杂志,2010,30(5)：504-508
[51]黄黎明,石晓强,梁恒.黄芪、山茱萸对肾炎小鼠尿蛋白谱的影响[J].中国中药杂志,2007,32(13)：1324-1328
[52]刘焕兰,陈炜,曲卫玲,等.应用蛋白质组学技术研究琼玉膏抗衰老的作用机制[J].现代中西医结合杂志,2010,19(29)：3814-3815
[53]龚文君,沃兴德,卢德赵,等.四物汤对血虚证模型大鼠肝线粒体蛋白质组的影响[J].中医杂志,2010,51(2)：160-163
[54]严冬梅,李敏军,刘秋君.四君子汤及党参对小鼠神经细胞蛋白质组表达的影响[J].时珍国医国药,2011,22(3)：602-603
[55]陈倩,谭彬,王应雄,等.自然流产患者蜕膜组织疾病特异蛋白的初步筛选与鉴定[J].重庆医学,2010,39(21)：2861-2863