宫腔粘连患者子宫内膜及粘连组织中TGF-β1、Smad3和IFN-γ的表达及意义
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摘要
背景和目的
宫腔粘连(intrauterine adheious IUA)是由于宫腔受到损伤或感染导致子宫内膜基底层受损,无法再生修复,宫腔内瘢痕形成而致宫腔形态失常,约90%由过度刮宫引起。近年来,随着宫腔操作机率的增加和宫腔镜技术的发展,IUA患病率呈逐年上升趋势,其发生严重影响现代妇女的生活质量及生育要求。目前,其发病机制尚不完全明确,可能与体内部分促进创面修复或抑制组织纤维化的细胞因子异常表达密切相关。为此,探讨TGF-β1、Smad3、IFN-γ在宫腔粘连中的表达,对于了解IUA的发病机制、为预防IUA的形成及术后复发、应用抗TGF-β抗体和TGF-β1抑制剂抗纤维化治疗提供重要的理论依据。
转化生长因子-β1(Transfer Growth Factor, TGF-β1)是目前公认的最强的促纤维化因子,是致组织纤维瘢痕形成通路中的关键介导因子。TGF-β1作为多功能细胞因子,通过与一些相关的炎性细胞因子相互作用,成纤维细胞大量增殖,细胞外基质过度沉积致组织纤维化；此外,TGF-β1通过对血管内皮细胞的趋化迁移及血管内皮生长因子(VEGF)的诱导作用,促进瘢痕组织血管的形成。
Smads蛋白家族主要包括Smad1～10, Smad3蛋白是将TGF-β活化并与受体结合产生的信号由胞质转导至胞核内的重要信号转导分子,通过TGF-β1/Smad3通路作用致胶原合成增加和细胞外基质沉积,促使组织纤维瘢痕形成。
干扰素-γ(interferon-gamma,IFN-γ)是目前比较明确的抑制组织纤维化的调节因子,具有影响细胞生长和分化以及免疫调节等多种生物学功能。IFN-y主要通过JAK/STAT途径促进Smad7表达的显著增加,造成TGF-β1/Smad3通路中信号的传递过程受阻,抑制TGF-β1和Smad3蛋白的表达,减少细胞外基质的沉积。
材料与方法
1.实验分组
研究组：选择2012年5月至2012年10月在我院行宫腔镜下宫腔粘连分离术的中重度宫腔粘连患者30例。依据取材部位的不同分为A组(粘连组织)和B组(靠近粘连的内膜组织)。
正常对照组：选择同期因不孕行宫腔镜检查且子宫内膜正常的非IUA患者30例,取其内膜,病理结果为增生期子宫内膜。
2.实验方法
采用免疫组织化学SP法分别检测TGF-β1、Smad3、IFN-γ在粘连组织、粘连旁内膜组织及非IUA患者正常内膜组织中的表达。以α=0.05为检验水准。
3.统计方法
全部实验数据输入SPSS17.0软件包处理。TGF-β1、Smad3、IFN-γ分别在粘连组织、粘连旁内膜组织及非IUA患者正常内膜组织中的表达采用单因素方差分析,组间两两采用LSD-t检验,各个因子之间的关联分析采用Pearson相关分析。
结果
1.TGF-β1的表达
(1) TGF-β1在粘连组织中的表达高于粘连旁内膜组织,差异有统计学意义(P<0.05)
(2) TGF-β1在粘连组织中的表达高于非IUA正常内膜组织,差异有统计学意义(P<0.05)
(3) TGF-β1在粘连旁内膜组织中的表达高于非IUA正常内膜组织,差异有统计学意义(P<0.05)
2.Smad3的表达
(1) Smad3在粘连组织中的表达高于粘连旁内膜组织,差异有统计学意义(P<0.05)
(2) Smad3在粘连组织中的表达高于非IUA正常内膜组织,差异有统计学意义(P<0.05)
(3)Smad3在粘连旁内膜组织中的表达高于非IUA正常内膜组织,差异有统计学意义(P<0.05)
3.IFN-γ的表达
(1) IFN-γ在粘连组织中的表达低于粘连旁内膜组织,差异有统计学意义(P<0.05)
(2) IFN-γ在粘连组织中的表达低于非IUA正常内膜组织,差异有统计学意义(P<0.05)
(3) IFN-γ在粘连旁内膜组织中的表达低于非IUA正常内膜组织,差异有统计学意义(P<0.05)
4.TGF-β1与Smad3蛋白在宫腔粘连组织及粘连旁内膜组织中的表达成正相关。(P<0.05,r1=0.96,r2=0.39)
5.TGF-β1与IFN-γ蛋白在宫腔粘连组织及粘连旁内膜组织中的表达成负相关。(P<0.05r1=-0.98,r2=-0.97)
结论
1.TGF-β1与Smad3在粘连组织及粘连旁内膜组织均呈高表达。且二者呈正相关,共同促进宫腔粘连的形成与发展。
2.IFN-γ在粘连组织及粘连旁内膜组织的表达均低于非IUA正常内膜中的表达,与TGF-β1呈负相关,其低表达与宫腔粘连形成相关。
3.以TGF-β1、Smad3和IFN-γ在TGF-β1/Smad3通路中的关系为出发点,为IUA的靶向治疗提供理论依据。
Background and Purpose
Intrauterine adhesions is caused by injuries or infections that induce intrauterine endometrium base layer damaged and irregenerative and intrauterine scar formation.These lead to the form of intrauterine abnormal which about90%is due to excessive curettage.In recent years,with the increase that the chance of uterine cavity operation and the development of modern hysteroscopy technology,its prevalence rate is increasing year by year,it seriously affected the modern women's quality of life and fertility requirements. So far the exact pathogenesis of Intrauterine adhesions is uncertain.It may be related to the abnormal expression of some cytokines promoting wound repair or inhibition of tissue fibrosis.Therefor,it is an important theoretical basis that to discuss the expression of TGF-β1、Smad3and IFN-γ in the fibrosis tissue and endomertrium near the fibrosis of patients with intrauterine adhesions,for the pathogenesis of Intrauterine adhesions,prevent the formation of IUA and postoperative recurrence and use of TGF-beta antibodies and TGF-beta1inhibitor anti fibrosis treatment
Now,TGF-β1is recognized as the strongest fibrosis factors,and it is the key mediating factor of fibrous scar formation pathways. TGF-β1as a kind of multifunctional cytokine induce tissue fibrosis, through interaction associated with some inflammatory cytokines, fibroblast proliferation in great quantities, excessive extracellular matrix deposition.Moreover, TGF-beta1through to chemotaxis migration of the vascular endothelial cell and entrainment of small tube skin growth factor (VEGF), promote blood vessels of the formation of scar tissue.
Smads proteins family including Smad1～10.Smad3protein is an important signal transduction molecule which transduces the signal originated from combination of TGF-beta activated and receptors from cytoplasmic to nuclei.Through the TGF-beta1/Smad3pathways to increase collagen synthesis and deposition of extracellular matrix, tissue fibrous scar formation.
It is the more cleat that IFN-gamma is the adjustment factor of restrain tissue fibrosis,It has a variety of biological functions,such as influence cell growth and differentiation,and immune regulation.Causes of TGF-beta1/Smad3pathway of signal in transmission process is blocked, inhibited TGF-beta1and Smad3protein expression,and reduce the deposition of extracellular matrix.
Material and Methods
1.Grouping
The experimental group:Take the fibrosis tissue and endomertrium near the fibrosis tissue in30patients dignosed as intrauterine adheious in department of gynaecology and obstetrics of the second affiliated hospital of Zhengzhou University from May2012to October2012.
The control group:Take normal endometrium in30infertility patients who were accepted hysteroscopic examination in depart tment of gynaecology and obstetrics of the second affiliated hospital of Zhengzhou University from May2012to October2012.Take normal intima proved by pathology.
2.Methods
Use Immunohistohistochemistry SP method to detect the expression of TGF-beta1, Smad3and IFN-γ in three tissue.
3.Statistical analysis
Using SPSS package for windows17.0statistical analysis to test all data.The expression of TGF-beta1, Smad3and IFN-y in three tissue is compared by Oneway ANOVA;Different binary comparison between the groups uses the LSD-t test.The correlation between groups is tested by Pearson correlation analysis.The level for significance tests is0.05.
Results
1. Expression of TGF-beta1
(1)The expression of TGF-betal in the fibrosis tissue is higher than that in endometrium near the fibrosis tissue.The difference is significant statistically (P<0.05).
(2)The expression of TGF-beta1in the fibrosis tissue is higher than that in normal endometrium tissue.The difference is significant statistically(P<0.05).
(3)The expression of TGF-beta1in endometrium near the fibrosis tissue is higher than that in normal endometrium tissue.The difference is significant statistically(P<0.05).
2.Expression of Smad3
(1)The expression of Smad3in the fibrosis tissue is higher than that in endometrium near the fibrosis tissue.The difference is significant statistically (P<0.05).
(2)The expression of Smad3in the fibrosis tissue is higher than that in normal endometrium tissue.The difference is significant statistically(P<0.05).
(3)The expression of Smad3in endometrium near the fibrosis tissue is higher than that in normal endometrium tissue.The difference is significant statistically (P<0.05).
3.Expression of IFN-γ
(1)The expression of IFN-γ in the fibrosis tissue is lower than that in endometrium near the fibrosis tissue.The difference is significant statistically (P<0.05).
(2)The expression of IFN-γ in the fibrosis tissue is lower than that in normal endometrium tissue.The difference is significant statistically(P<0.05).
(3)The expression of IFN-γ in endometrium near the fibrosis tissue is lower than that in normal endometrium tissue.The difference is significant statistically(P<0.05).
4.Relationship between TGF-beta1and Smad3
There is a positive correlation between the expression of TGF-betal and the expression of Smad3in the fibrosis tissue and in endometrium near the fibrosis tissue.
5.Relationship between TGF-betal and IFN-γ
There is a negative correlation between the expression of TGF-betal and the expression of IFN-γ in the fibrosis tissue and in endometrium near the fibrosis tissue.
Conclusions
1.TGF-betal and Smad3are higher expressions in the fibrosis tissue and in endometrium near the fibrosis tissue,which related to the formation of Intrauterine adhesions.
2.IFN-γ is lower expression in the fibrosis tissue and in endometrium near the fibrosis tissue.There is a negative correlation between the expression of TGF-betal and the expression of IFN-γ, which related to the formation of Intrauterine adhesions.
3.Through the relationship of TGF-beta1, Smad3and IFN-γ in TGF-beta1/Smad3pathways, the anti fibrosis treatment is likely to be used in the treatment of uterine cavity adhesion.
宫腔粘连(intrauterine adheious IUA)是由于宫腔受到损伤或感染导致子宫内膜基底层受损,无法再生修复,宫腔内瘢痕形成而致宫腔形态失常,约90%由过度刮宫引起。近年来,随着宫腔操作机率的增加和宫腔镜技术的发展,IUA患病率呈逐年上升趋势,其发生严重影响现代妇女的生活质量及生育要求。目前,其发病机制尚不完全明确,可能与体内部分促进创面修复或抑制组织纤维化的细胞因子异常表达密切相关。为此,探讨TGF-β1、Smad3、IFN-γ在宫腔粘连中的表达,对于了解IUA的发病机制、为预防IUA的形成及术后复发、应用抗TGF-β抗体和TGF-β1抑制剂抗纤维化治疗提供重要的理论依据。
转化生长因子-β1(Transfer Growth Factor, TGF-β1)是目前公认的最强的促纤维化因子,是致组织纤维瘢痕形成通路中的关键介导因子。TGF-β1作为多功能细胞因子,通过与一些相关的炎性细胞因子相互作用,成纤维细胞大量增殖,细胞外基质过度沉积致组织纤维化；此外,TGF-β1通过对血管内皮细胞的趋化迁移及血管内皮生长因子(VEGF)的诱导作用,促进瘢痕组织血管的形成。
Smads蛋白家族主要包括Smad1～10, Smad3蛋白是将TGF-β活化并与受体结合产生的信号由胞质转导至胞核内的重要信号转导分子,通过TGF-β1/Smad3通路作用致胶原合成增加和细胞外基质沉积,促使组织纤维瘢痕形成。
干扰素-γ(interferon-gamma,IFN-γ)是目前比较明确的抑制组织纤维化的调节因子,具有影响细胞生长和分化以及免疫调节等多种生物学功能。IFN-y主要通过JAK/STAT途径促进Smad7表达的显著增加,造成TGF-β1/Smad3通路中信号的传递过程受阻,抑制TGF-β1和Smad3蛋白的表达,减少细胞外基质的沉积。
材料与方法
1.实验分组
研究组：选择2012年5月至2012年10月在我院行宫腔镜下宫腔粘连分离术的中重度宫腔粘连患者30例。依据取材部位的不同分为A组(粘连组织)和B组(靠近粘连的内膜组织)。
正常对照组：选择同期因不孕行宫腔镜检查且子宫内膜正常的非IUA患者30例,取其内膜,病理结果为增生期子宫内膜。
2.实验方法
采用免疫组织化学SP法分别检测TGF-β1、Smad3、IFN-γ在粘连组织、粘连旁内膜组织及非IUA患者正常内膜组织中的表达。以α=0.05为检验水准。
3.统计方法
全部实验数据输入SPSS17.0软件包处理。TGF-β1、Smad3、IFN-γ分别在粘连组织、粘连旁内膜组织及非IUA患者正常内膜组织中的表达采用单因素方差分析,组间两两采用LSD-t检验,各个因子之间的关联分析采用Pearson相关分析。
结果
1.TGF-β1的表达
(1) TGF-β1在粘连组织中的表达高于粘连旁内膜组织,差异有统计学意义(P<0.05)
(2) TGF-β1在粘连组织中的表达高于非IUA正常内膜组织,差异有统计学意义(P<0.05)
(3) TGF-β1在粘连旁内膜组织中的表达高于非IUA正常内膜组织,差异有统计学意义(P<0.05)
2.Smad3的表达
(1) Smad3在粘连组织中的表达高于粘连旁内膜组织,差异有统计学意义(P<0.05)
(2) Smad3在粘连组织中的表达高于非IUA正常内膜组织,差异有统计学意义(P<0.05)
(3)Smad3在粘连旁内膜组织中的表达高于非IUA正常内膜组织,差异有统计学意义(P<0.05)
3.IFN-γ的表达
(1) IFN-γ在粘连组织中的表达低于粘连旁内膜组织,差异有统计学意义(P<0.05)
(2) IFN-γ在粘连组织中的表达低于非IUA正常内膜组织,差异有统计学意义(P<0.05)
(3) IFN-γ在粘连旁内膜组织中的表达低于非IUA正常内膜组织,差异有统计学意义(P<0.05)
4.TGF-β1与Smad3蛋白在宫腔粘连组织及粘连旁内膜组织中的表达成正相关。(P<0.05,r1=0.96,r2=0.39)
5.TGF-β1与IFN-γ蛋白在宫腔粘连组织及粘连旁内膜组织中的表达成负相关。(P<0.05r1=-0.98,r2=-0.97)
结论
1.TGF-β1与Smad3在粘连组织及粘连旁内膜组织均呈高表达。且二者呈正相关,共同促进宫腔粘连的形成与发展。
2.IFN-γ在粘连组织及粘连旁内膜组织的表达均低于非IUA正常内膜中的表达,与TGF-β1呈负相关,其低表达与宫腔粘连形成相关。
3.以TGF-β1、Smad3和IFN-γ在TGF-β1/Smad3通路中的关系为出发点,为IUA的靶向治疗提供理论依据。
Background and Purpose
Intrauterine adhesions is caused by injuries or infections that induce intrauterine endometrium base layer damaged and irregenerative and intrauterine scar formation.These lead to the form of intrauterine abnormal which about90%is due to excessive curettage.In recent years,with the increase that the chance of uterine cavity operation and the development of modern hysteroscopy technology,its prevalence rate is increasing year by year,it seriously affected the modern women's quality of life and fertility requirements. So far the exact pathogenesis of Intrauterine adhesions is uncertain.It may be related to the abnormal expression of some cytokines promoting wound repair or inhibition of tissue fibrosis.Therefor,it is an important theoretical basis that to discuss the expression of TGF-β1、Smad3and IFN-γ in the fibrosis tissue and endomertrium near the fibrosis of patients with intrauterine adhesions,for the pathogenesis of Intrauterine adhesions,prevent the formation of IUA and postoperative recurrence and use of TGF-beta antibodies and TGF-beta1inhibitor anti fibrosis treatment
Now,TGF-β1is recognized as the strongest fibrosis factors,and it is the key mediating factor of fibrous scar formation pathways. TGF-β1as a kind of multifunctional cytokine induce tissue fibrosis, through interaction associated with some inflammatory cytokines, fibroblast proliferation in great quantities, excessive extracellular matrix deposition.Moreover, TGF-beta1through to chemotaxis migration of the vascular endothelial cell and entrainment of small tube skin growth factor (VEGF), promote blood vessels of the formation of scar tissue.
Smads proteins family including Smad1～10.Smad3protein is an important signal transduction molecule which transduces the signal originated from combination of TGF-beta activated and receptors from cytoplasmic to nuclei.Through the TGF-beta1/Smad3pathways to increase collagen synthesis and deposition of extracellular matrix, tissue fibrous scar formation.
It is the more cleat that IFN-gamma is the adjustment factor of restrain tissue fibrosis,It has a variety of biological functions,such as influence cell growth and differentiation,and immune regulation.Causes of TGF-beta1/Smad3pathway of signal in transmission process is blocked, inhibited TGF-beta1and Smad3protein expression,and reduce the deposition of extracellular matrix.
Material and Methods
1.Grouping
The experimental group:Take the fibrosis tissue and endomertrium near the fibrosis tissue in30patients dignosed as intrauterine adheious in department of gynaecology and obstetrics of the second affiliated hospital of Zhengzhou University from May2012to October2012.
The control group:Take normal endometrium in30infertility patients who were accepted hysteroscopic examination in depart tment of gynaecology and obstetrics of the second affiliated hospital of Zhengzhou University from May2012to October2012.Take normal intima proved by pathology.
2.Methods
Use Immunohistohistochemistry SP method to detect the expression of TGF-beta1, Smad3and IFN-γ in three tissue.
3.Statistical analysis
Using SPSS package for windows17.0statistical analysis to test all data.The expression of TGF-beta1, Smad3and IFN-y in three tissue is compared by Oneway ANOVA;Different binary comparison between the groups uses the LSD-t test.The correlation between groups is tested by Pearson correlation analysis.The level for significance tests is0.05.
Results
1. Expression of TGF-beta1
(1)The expression of TGF-betal in the fibrosis tissue is higher than that in endometrium near the fibrosis tissue.The difference is significant statistically (P<0.05).
(2)The expression of TGF-beta1in the fibrosis tissue is higher than that in normal endometrium tissue.The difference is significant statistically(P<0.05).
(3)The expression of TGF-beta1in endometrium near the fibrosis tissue is higher than that in normal endometrium tissue.The difference is significant statistically(P<0.05).
2.Expression of Smad3
(1)The expression of Smad3in the fibrosis tissue is higher than that in endometrium near the fibrosis tissue.The difference is significant statistically (P<0.05).
(2)The expression of Smad3in the fibrosis tissue is higher than that in normal endometrium tissue.The difference is significant statistically(P<0.05).
(3)The expression of Smad3in endometrium near the fibrosis tissue is higher than that in normal endometrium tissue.The difference is significant statistically (P<0.05).
3.Expression of IFN-γ
(1)The expression of IFN-γ in the fibrosis tissue is lower than that in endometrium near the fibrosis tissue.The difference is significant statistically (P<0.05).
(2)The expression of IFN-γ in the fibrosis tissue is lower than that in normal endometrium tissue.The difference is significant statistically(P<0.05).
(3)The expression of IFN-γ in endometrium near the fibrosis tissue is lower than that in normal endometrium tissue.The difference is significant statistically(P<0.05).
4.Relationship between TGF-beta1and Smad3
There is a positive correlation between the expression of TGF-betal and the expression of Smad3in the fibrosis tissue and in endometrium near the fibrosis tissue.
5.Relationship between TGF-betal and IFN-γ
There is a negative correlation between the expression of TGF-betal and the expression of IFN-γ in the fibrosis tissue and in endometrium near the fibrosis tissue.
Conclusions
1.TGF-betal and Smad3are higher expressions in the fibrosis tissue and in endometrium near the fibrosis tissue,which related to the formation of Intrauterine adhesions.
2.IFN-γ is lower expression in the fibrosis tissue and in endometrium near the fibrosis tissue.There is a negative correlation between the expression of TGF-betal and the expression of IFN-γ, which related to the formation of Intrauterine adhesions.
3.Through the relationship of TGF-beta1, Smad3and IFN-γ in TGF-beta1/Smad3pathways, the anti fibrosis treatment is likely to be used in the treatment of uterine cavity adhesion.
引文
[1]Haver stock BD. Hypertrophic scars and keloids[J].C lin Pediatric Med Surg,2001,18:147-159.
[2]成九梅,靳琳,夏恩兰等.雌孕激素受体及转化生长因子β1在宫腔粘连发病机制中的作用[J].中国实用妇科与产科杂志,2005,21(9)：539-541.
[3]Itoh S,Thoria M,M Elucidation of Smad requirement in transforming growth factor beta type I receptor induced responses [J],2003.06.
[4]于蓉,岑瑛TGF-β1/Smad3信号转导通路与创伤后瘢痕形成[J].中国修复重建外科杂志,2012,26(3)：330-335.
[5]Flanders KC.Smad3 as a mediator of the fibrotic response[J]. Int J Exp Pathol,2004,85(2): 47-64.
[6]Gordon KJ, Blobe GC. Role of transforming growth factor-beta super-family signaling pathways in human disease[J]. Biochim Biophys Acta,2008,1782(4):197-228.
[7]王丹茹.改变Smad表达对成纤维细胞生物特性的影响[D].上海.上海第二医科大学.2003.10-11.
[8]夏恩兰,主编.妇科内镜学及图谱[M].北京：人民卫生出版社,2001,17.
[9]邓凌,农晓琳.病理性瘢痕与细胞因子相关性研究进展[J].中国烧伤创疡杂志.2009,21(3)：223-226.
[10]成九梅,段华,夏恩兰.宫腔粘连患者子宫内膜基质金属蛋白酶-9 (MMP-9) [J].中国妇幼保健2007,22(18)：2574-2572.
[11]Hasegawa T, Nakao A, Sumiyoshi K etal, IFN-gamma fails to antagonize fibrotic effect of TGF-beto on keloid-derived dermal fibroblasts. J Dermatol Sci,2003,32(1):19-24.
[12]Lee TY,Chin GS,Kim WJ,etal.Expression of transformin grow factor betal 2 and 3 protein in keloids [J].Ann Pla Surg,1999,43:179-184.
[13]Kim CW, Suh S, Sung SH etal A transcriptional factor decoy against AP-1 suppresses TGF-betal-induced type 1 collagen gene expression in cultured keloid Fibroblasts. J Dermatol Sci,2005,37(1):49-51.
[14]Falanga A,Grinnel F,Gilchrest B,etal.Experimental approaches to chronicwounds[J].Wound Rep Reg,1999,8:132-135.
[15]Olsson N, Piek E, Sundstrom M, etal. Transforming growth factor beta mediatedmast cell migration depends on mitogenactivated protein kinase activity[J].CellSignal,2007.13(7): 483-490.
[16]Ishida W,Mori Y,Lakos GS,etal. Intracellular TGF-beta receptor blockadeabrogates Smad-dependent fibroblast activation in vitro and in vivo[J].Invest Dermatol,2006,126(8): 1733-1744.
[17]Volker R.Stoldt,Oliver Schnorr,etal.Transforming growth factor-β1 enhances the antifibrinolytic and prothrombotic state of growing endothelial cells in a cell cycle-specific manner.The FASEB Journal,2006,20(5):965-973.
[18]刘琳琳,刘玉环.CTGF和TGF-β1l的表达与宫腔粘连形成的相关性[J].山东医药,2012,52(12)：17-19.
[19]陈伟,付小兵,孙同柱等.TGF-β异构体及其受体在胎儿和成人皮肤中的表达[J].临床与实验病理学杂志.2003,19(4)：393-395.
[20]Colwell AS, Krummel TM,Longaker MT,etal.Fetal and adult fibroblasts have similar TGF-bata-midiated, Smad-dependent signaling pathways.Plast Reconstr Surg,2006,117(7): 2277-2283.
[21]Sekelsky JJ,Newfeld SJ, Raftery LA,etal. Genetic characterization and cloning of mothers against dpp, a gene required for decapentaplegic function in Drosophils melanogaster[J]. Genestics 1995,139(3):1347-1358.
[22]Shi Y,Massague J. Mechanisms of TGF-P signaling from cell membrane to the nucleus[J]. Cell,2003,113(6):658-70.
[23]Yuan W,Varga J.Transforming growthfactor-beta repression of matrix metallo proteinase-1 in dermal fibroblasts involves Smad3[J].J Biol Chem,2001,276(42):38502-38510.
[24]Flanders KC,Sullivan CD,Fujii M,etal. Mice lacking Smad3 are protected against cutaneous injury induced by ionzing radiation.Am J Pathol,2002,160:1057-1068.
[25]徐林敏,茹雪莹,吴泰相IFN-y与银屑病相关性的Meta分析[J].中国询证医学杂志.2007.7(7)：516-522.
[26]刘春宇,顾振伦,张克平,等.沙苑子黄酮抗CC14大鼠肝纤维化作用及对IFN-γ,TGF-β1的影响[J].中国药学杂志.2004,39(12).910-912.
[27]Zhang XF,Guo SZ,Lu KH,etal.Different roles of PKC and PKA in effect of interferon-gamma on proliferation and collagen synthesis of fibroblasts.Acta Pharmaco Sin,2004,25:1320-1326.
[28]李繁丽,李繁云,郑维国,等.重组人干扰素-γ联合激素治疗特发性肺间质纤维化临床观察[J].河北医药.2012,34(3)：328-239.
[29]刘志宏.IFN-γ对胆管损伤后瘢痕成纤维细胞的影响[D].山西.山西医科大学.2011.6-7.
[30]Kondou H,Mushiake S,Etani Y,etal.A blocking peptide for transforming growth factor-betal activation prevents hepatic fibrosis in vivo[J].2003,39(5):742-748.
[31]Ning XH,Ge XF,Cui Y.Ulinastatininhibits unilateral ureteral obstruction-induced renal interstitial fibrosis in rats via transforming growth factor beta(TGF-beta)/Smad signalling pathways[J].Int Immunopharmacol,2013,15(2):406-413.
[32]Yu H,Konigshoff M,Jayachandran A,etal.Transgelin is a direct target of TGF-beta/Smad3 dependent epithelial cell migration in lung fibtosis[J].FASEB J,2008,22(6):1778-1789.
[33]郭旭.尿液、尿酸对人尿道成纤维细胞TGF-β1、Smad3影响实验研究[D].重庆.第三军医大学.2009.56.
[34]Yuan S,Jing H.Cardiac pathologies in relation to Smad-dependent pathways[J].Interact Cardio Vasc Thorac Surg,2010,11(4):455-460.
[35]Nakao A,Afrakhte M,Moren A. Identification of Smad7,a TGf-βinducible antagonist of TGF-β signaling [J].Nature.1997,39(9):631-635.
[36]Shi Y, Massague J. Mechanisms of TGF-beta signaling from cell membrane to the nucleus. Cell.2003;113(6):685-700.
[37]Zheng R,Xiong Q,Zuo B,etal.Using RNA intere]ference to identify rhe different roles of SMAD2 and SMAD3 in NIH/3T3 fibroblast cells [J].Cell Biochem Funct,2008,26(5):548-556.
[38]陈伟,付小兵,王海滨等.增生性瘢痕形成和成熟过程中转化生长因子β及下游信号分子的基因表达变化.中华实验外科杂志,2005,22(6)：740-742.
[39]Whitman M.Signal transduction,feedback from inhibitory SMADs[J].Nature,1997,389: 549-551.
[40]Kolb M,Margetts PJ,Galt T,etal. Transient transgene expession of decorin in the lung reduces the fibrotic response to blemycin [J].Am J Respir Crit Care Med 2001,163(3):770-777.
[41]Lin RY,Sullivan KM,Argenta PA,etal.Exogenous transforming growth factor-beta amolifies its own expression and induces scar formation in amodel of human fetal skin repair[J]. AnnSurg,1955,222:146-454.
[42]董祥林,马少林.转化生长因子β在纤维化疾病中的研究与应用[J].中国临床康复.2004,8(35)：8050-8051.
[1]Asherman JG. Amenorrhoea traumatica (atretica) [J]. J Obstet Gynaecol Br Emp,1948, 55(1):23-30.
[2]Yu D, Wong YM, Cheong Y, et al. Asherman syndrome:one century later[J]. Fertil Steril, 2008,89(4):759-779.
[3]罗丽兰.不孕与不育[M].北京：人民卫生出版社,2009.241-242.
[4]Lonnroth K, Raviglione M. Global epidemiology of tuberculosis:prospects for control[J]. Semin Respir Crit Care Med 2008;29:481-491.
[5]李敏.王蔼明,商微,等.不同程度宫腔粘连相关影响因素及临床特征研究[J].人民军医.55(12)：1199-1200.
[6]Friedler S, Margalioth EJ, Kafka I, et al.Incidence of post-abortion intrauterine adhesions evaluated by hysteroscopy--aprospective study[J]. Hum Reprod,1993,8(3):442-444.
[7]Allnany H.Intrauterine adhesions[J].Acta Obstet Gynecol Scand.2001,80(11):986-993.
[8]Taskin O, Sadik S, Onoglu A, et al. Role of endometrial supression on the frequency of intrauterine adhesions after resectoscopic surgery[J].J Am Assoc Gynecol Laparosc,2000, 7(3):351-354.
[9]康美花,田春芳.宫腔粘连的临床研究进展[J].医学综述.2011,17(9)：1350-1353.
[10]韩义娜,任琛琛,申爱荣等.VEGF在宫腔粘连患者子宫内膜中的表达及与IL-18、TNF-α的关系[J].中国妇幼保健,2011,26(29)：4497-4499.
[11]雷琳,郑永才,陈志华.药物流产后出血的病理及相关因素分析[J].中国优生与遗传杂志,2004,12(3)：127-128.
[12]Caroline EG，David H.Generating receptive endomertrium in Asherman's syndrome[J].J Hum Reprod Sci,2011,4(1):49-52.
[13]Taylor E, Gomel V. The uterus and fertility[J]. Fertil Steril 2008;89:1-16.
[14]Berman JM.Intrauterine adhesions[J].Semin Reprod Med 2008;26:349-355.
[15]Nasr AT,A1-Inany HG,Thabet SM,etal.A clinicohysteroscopic scoring system of intrauterine adhesions[J].Gynecol Obstet Invest,2000,50(3):178-181.
[16]Sohail S.Uterine sonomorphology of Asherman syndrome on trans-vaginal ultrasound [J]. Pak J Med Sci,2005,21:451-454.
[17]Salle B,Gaucherand P,Hilaire PS,etal.Transvaginal sonohysterographic evaluation of intrauterine adhesion [J].J Clin Ultrasound,1999,27:131-134.
[18]蒋贤辉,赵博文,余婵,三维经阴道超声诊断宫腔粘连的临床应用[J].浙江医学,2011,33(3)：434-435.
[19]Cosmi E,Saccardi C,Litta P,etal.Transvaginal ultra-sound and sonohysterography for assessment of postpartum residual trophoblastic tissue[J].Int J Gynaecol Obstet,2010,110(3): 262-264.
[20]Soares SR,Barbosa dos Reis MM,Camargos AF.Diagnostic accura-cy of sonohysterography, transvaginal sonography,and hyste rosal-pingography in patients with uterine cavity diseases [J].Fertil Ster-Il,2000,73(2):406-411.
[21]夏恩兰.妇科内镜学[M].北京.人民卫生出版社,2001：104-107.
[22]Robinson J K,Colimon L M,Saacson K B.etal.Postoperative adhesiolysis therapy for intrauterine adhesions (Asherman's syndrome)[J].Fertil Steril,2008,90(2):409-414.
[23]Thomson A J,Abbott J A,Deans R,etal.The management of intrauterine synechiae[J].Curr Opin Obstet Gynecol,2009,21(4):335-341.
[24]张琳.子宫输卵管造影的临床进展和现状分析[J].中国实用医药,2011,6(7)：68-69.
[25]Sharma J B,Roy K K,Pushparaj M, etal. Genital tuberculosis:an important cause of Asherman's syndrome in India [J]. Arch Gyne-col Obstet,2008,277(1):37-41.
[26]Deans R,Abbott J.Review of intrauterine adhesions[J].J Minim Invasive Gynecol,2010, 17(5),555-569.
[27]Salamonsen,L.A.Tissue injury and repair in the female human reproductive tract[J]. Reproduction,2003.125(3):301-311.
[28]乐杰.妇产科学[M].7版.北京：人民卫生出版社,2008：6.
[29]Garry R,Hart R,Karthigasu KA,etal.Structural changes in endometrial basal glands during menstruation[J].BJOG,2010,117:1175-1185.
[30]Haruchika Masuda,Christoph Kalka,Tomono Takahashi etal.Estrogen-mediated endothelial progenitor cell biology and kinetics for physiological postnatal vasculogenesis[J]. Circ Res. 2007,101:598-606.
[31]Larson BJ, Longaker MT, Lorenz HP. Scarless fetal wound healing:a basic science review[J]. Plast Reconstr Surg.2010,126(4):1172-1180.
[32]Padykula HA. Regeneration in the primate uterus:the role of stem cells[J]. Ann N Y Acad Sci 1991;622:47-56.
[33]Chan, R.W. and C.E. Gargett, Identification of label-retaining cells in mouse endometrium[J]. Stem Cells,2006.24(6):1529-1538.
[34]Amer MI, Abd-EL-Maeboud KH. Anmion graft following hysteroscopic lysis of intrauterine adhesions[J] J ObstetGynaecol Res,2006,32 (6):559-566.
[35]段华.微创妇科全真手术[M].北京.江苏科学技术出版社,2008：102.
[36]夏恩兰.宫腔镜并发症防治的现代观点[J].国际妇产科学杂志.2008,35(5)：387-390.
[37]Leuschner H,Riedel HH,Anders M.Hysteroscopic survey from 1994 to 1996 in the eastem part of Gemany[J].J Am Assoc Gynecol Laparosc,1997,4(4Suppl):S28.
[38]Yasmin H,Nasir A,Noorani K J.Hysteroscopic management of Asherman's syndrome[J].J Pak Med Assoc,2007,57(11):553-555.
[39]Vesce F, Jorizzo G, Bianciotto A, et a.l Use of the copper intrauterine device in themanagement of secondary amen-orrhea[J].FertilSteri,l 2000,73:162-165.
[40]AlInany H.Intrauterine adhesions[J].Acta Obstet Gynecol S cand,2001,80:986-993.
[41]王淑贞,主编.实用妇产科学[M].北京.人民卫生出版社,1987,568-569.
[42]南秀牌,韩丽晖,吴明辉.宫内节育器并发宫颈宫腔粘连17例临床分析[J].实用妇产科杂志,2003,19(6)：369-370.
[43]范懿隽,卫兵,张妤.中重度宫腔粘连分离术后预防再粘连的临床研究[J].安徽医科大学学报,2011,46(4)：374-375.
[44]Lin JC,Chen YO,Chang CC,etal.Novel adjunctive treatment for cervical adhesion with cros-type nelaton catheter; a preliminary report and literature rewiew[J].Taiwan J Obstet Gynecol,2007,46(1):38-42.
[45]柳洁.宫腔粘连分离术后两种抗宫腔再粘连方法预后分析[J].中国误诊学杂志,2011,11(18)：4322.
[46]Robinson JK, Colimon LMS, Isaacson KB. Postoperative adhesiolysis therapy for intrauterine adhesions (Asherman's syndrome)[J].Fertil Steril,2008,90(2):409.
[47]赵永红.徐颖.透明质酸钠凝胶预防剖宫产后宫腔粘连的临床应用[J].中国组织工程研究与临床康复.2011,15(12)：2217-2220.
[48]Dilege E,Codam H.Prevention of adhesion to prosthetic mesh in incisional velltral hernias:comparison of different barriers in an experimen-talmodel.Surg Techol Int,2005, 14(7):185-190.
[49]康庆芝.应用综合方法预防宫腔粘连分离术后粘连的疗效分析[J].中外医疗,2010,40(7)：69-70.
[50]Liu Y,Cheng JM,Duang H,etal.Employment of intrauterine fibrin sealant with water bag instead of intrauterine device after laparoscopy combined with hysteroscopy transcervical resection of septus[J].Medical Jourmal of Wuhan University,2007,28(3):376-378.
[51]赵福杰,李妍,王敏等.生物蛋白胶在宫腔镜下宫腔粘连分离术后预防再次粘连的价值[J].中国内镜杂志,2008,14(11)：1131-1135.
[52]聂桂香.医用几丁糖凝胶预防输卵管复通后的粘连[J].中国组织工程研究与临床康复,2011,15(29)：5413-5416.
[53]侯春林.几丁糖生物学结构性研究[J].中国修复重建外科杂志,1993,7(2)：115.
[54]刘鑫磊.几丁糖防治介入治疗输卵管复通后再粘连的临床研究[J].中国妇幼保健.2005,23：3139-3140.
[55]Akle CA, Adinlfi M, Welsh KI, et al. Immunogenicity of human amniotic epithelial cells after transplantation into volunteers. Lancet,1981,2(8254):1003-5.
[56]Amer MI, Abdel Maeboud KH. Amnion graft following hysteroscopic lysis of intrauterine adhesions [J]. J Obstet Gynaecol Res,2006,32(6):559.
[57]Amer MI, Elmaeboud KH, Abdelfatah I,etal.Human amnion as a temporary biologic barrier after hysteroscopiclysis of severe intrauterine adhesions:pilot study [J] J Minim Invasive Gynecol,2010,17(5):605-611.
[58]彭雪冰,夏恩兰.羊膜宫腔内植入+人工周期治疗中、重度宫腔粘连的安全性及有效性[J].生殖与避孕.2012,32(12)：857-860.
[59]T seng SCG, LiD-Q,Ma X.Down-regulation of TGF-β1,β2,β3 and TGG-βreceptor II expression in human corneal broblasts by amniotic membrane[J]. Invest Ophthalmol Vis Sci 1998,39:428.
[60]Pabuccu R, Onalan G, Kaya C et al. Efficiency and pregnancy outcome of serial intrauterine device guided hysteroscopic adhesiolysis of intrauterine synechiae[J]. Fertil Steril,2008, 90(5):1973.
[61]牟晓玲.戊酸雌二醇在宫腔粘连中的治疗作用[J].中国妇幼保健.2010,25(9)：1274-1275.
[62]刘玉环,赵玉婷,蒋东桥等.大剂量雌激素对中重度宫腔粘连预后的影响[J].山东医药,2012,52(12)：14-16.
[63]Zinger M, Liu JH, Thomas MA. Successful use of vaginal sildenafil citrate in two infertility patients with Asherman's syndrome[J]. J Women's Health,2006,15(4):442.
[64]余世强,吴文清,李江等.通络补肾法合人工周期防治重度宫腔粘连术后再粘连临床研究[J].新中医.2011,43(11)：46-47.
[65]孙永忠.益肾活血调冲汤治疗宫腔粘连性不孕50例[J].山东中医杂志,2010,29(3)：167-168.
[66]Ju S,Teng GJ,Lu H, In vivo differentiation of magnetically labeled mesenchymal stemcells into hepatocytes for celltherapy to repair damaged liver [J].In vest Radiol.2010,45(10): 625-633.
[67]Diep CQ, Ma D, Deo RC, et al. Identification of adult nephron progenitors capable of kidney regeneration inzebrafish.Nature.2011.470(7332):95-100.
[68]赵潇丹.小鼠骨髓间充盾干细胞对子宫内膜损伤修复的初步研究[D].郑州.郑州大学,21.
[2]成九梅,靳琳,夏恩兰等.雌孕激素受体及转化生长因子β1在宫腔粘连发病机制中的作用[J].中国实用妇科与产科杂志,2005,21(9)：539-541.
[3]Itoh S,Thoria M,M Elucidation of Smad requirement in transforming growth factor beta type I receptor induced responses [J],2003.06.
[4]于蓉,岑瑛TGF-β1/Smad3信号转导通路与创伤后瘢痕形成[J].中国修复重建外科杂志,2012,26(3)：330-335.
[5]Flanders KC.Smad3 as a mediator of the fibrotic response[J]. Int J Exp Pathol,2004,85(2): 47-64.
[6]Gordon KJ, Blobe GC. Role of transforming growth factor-beta super-family signaling pathways in human disease[J]. Biochim Biophys Acta,2008,1782(4):197-228.
[7]王丹茹.改变Smad表达对成纤维细胞生物特性的影响[D].上海.上海第二医科大学.2003.10-11.
[8]夏恩兰,主编.妇科内镜学及图谱[M].北京：人民卫生出版社,2001,17.
[9]邓凌,农晓琳.病理性瘢痕与细胞因子相关性研究进展[J].中国烧伤创疡杂志.2009,21(3)：223-226.
[10]成九梅,段华,夏恩兰.宫腔粘连患者子宫内膜基质金属蛋白酶-9 (MMP-9) [J].中国妇幼保健2007,22(18)：2574-2572.
[11]Hasegawa T, Nakao A, Sumiyoshi K etal, IFN-gamma fails to antagonize fibrotic effect of TGF-beto on keloid-derived dermal fibroblasts. J Dermatol Sci,2003,32(1):19-24.
[12]Lee TY,Chin GS,Kim WJ,etal.Expression of transformin grow factor betal 2 and 3 protein in keloids [J].Ann Pla Surg,1999,43:179-184.
[13]Kim CW, Suh S, Sung SH etal A transcriptional factor decoy against AP-1 suppresses TGF-betal-induced type 1 collagen gene expression in cultured keloid Fibroblasts. J Dermatol Sci,2005,37(1):49-51.
[14]Falanga A,Grinnel F,Gilchrest B,etal.Experimental approaches to chronicwounds[J].Wound Rep Reg,1999,8:132-135.
[15]Olsson N, Piek E, Sundstrom M, etal. Transforming growth factor beta mediatedmast cell migration depends on mitogenactivated protein kinase activity[J].CellSignal,2007.13(7): 483-490.
[16]Ishida W,Mori Y,Lakos GS,etal. Intracellular TGF-beta receptor blockadeabrogates Smad-dependent fibroblast activation in vitro and in vivo[J].Invest Dermatol,2006,126(8): 1733-1744.
[17]Volker R.Stoldt,Oliver Schnorr,etal.Transforming growth factor-β1 enhances the antifibrinolytic and prothrombotic state of growing endothelial cells in a cell cycle-specific manner.The FASEB Journal,2006,20(5):965-973.
[18]刘琳琳,刘玉环.CTGF和TGF-β1l的表达与宫腔粘连形成的相关性[J].山东医药,2012,52(12)：17-19.
[19]陈伟,付小兵,孙同柱等.TGF-β异构体及其受体在胎儿和成人皮肤中的表达[J].临床与实验病理学杂志.2003,19(4)：393-395.
[20]Colwell AS, Krummel TM,Longaker MT,etal.Fetal and adult fibroblasts have similar TGF-bata-midiated, Smad-dependent signaling pathways.Plast Reconstr Surg,2006,117(7): 2277-2283.
[21]Sekelsky JJ,Newfeld SJ, Raftery LA,etal. Genetic characterization and cloning of mothers against dpp, a gene required for decapentaplegic function in Drosophils melanogaster[J]. Genestics 1995,139(3):1347-1358.
[22]Shi Y,Massague J. Mechanisms of TGF-P signaling from cell membrane to the nucleus[J]. Cell,2003,113(6):658-70.
[23]Yuan W,Varga J.Transforming growthfactor-beta repression of matrix metallo proteinase-1 in dermal fibroblasts involves Smad3[J].J Biol Chem,2001,276(42):38502-38510.
[24]Flanders KC,Sullivan CD,Fujii M,etal. Mice lacking Smad3 are protected against cutaneous injury induced by ionzing radiation.Am J Pathol,2002,160:1057-1068.
[25]徐林敏,茹雪莹,吴泰相IFN-y与银屑病相关性的Meta分析[J].中国询证医学杂志.2007.7(7)：516-522.
[26]刘春宇,顾振伦,张克平,等.沙苑子黄酮抗CC14大鼠肝纤维化作用及对IFN-γ,TGF-β1的影响[J].中国药学杂志.2004,39(12).910-912.
[27]Zhang XF,Guo SZ,Lu KH,etal.Different roles of PKC and PKA in effect of interferon-gamma on proliferation and collagen synthesis of fibroblasts.Acta Pharmaco Sin,2004,25:1320-1326.
[28]李繁丽,李繁云,郑维国,等.重组人干扰素-γ联合激素治疗特发性肺间质纤维化临床观察[J].河北医药.2012,34(3)：328-239.
[29]刘志宏.IFN-γ对胆管损伤后瘢痕成纤维细胞的影响[D].山西.山西医科大学.2011.6-7.
[30]Kondou H,Mushiake S,Etani Y,etal.A blocking peptide for transforming growth factor-betal activation prevents hepatic fibrosis in vivo[J].2003,39(5):742-748.
[31]Ning XH,Ge XF,Cui Y.Ulinastatininhibits unilateral ureteral obstruction-induced renal interstitial fibrosis in rats via transforming growth factor beta(TGF-beta)/Smad signalling pathways[J].Int Immunopharmacol,2013,15(2):406-413.
[32]Yu H,Konigshoff M,Jayachandran A,etal.Transgelin is a direct target of TGF-beta/Smad3 dependent epithelial cell migration in lung fibtosis[J].FASEB J,2008,22(6):1778-1789.
[33]郭旭.尿液、尿酸对人尿道成纤维细胞TGF-β1、Smad3影响实验研究[D].重庆.第三军医大学.2009.56.
[34]Yuan S,Jing H.Cardiac pathologies in relation to Smad-dependent pathways[J].Interact Cardio Vasc Thorac Surg,2010,11(4):455-460.
[35]Nakao A,Afrakhte M,Moren A. Identification of Smad7,a TGf-βinducible antagonist of TGF-β signaling [J].Nature.1997,39(9):631-635.
[36]Shi Y, Massague J. Mechanisms of TGF-beta signaling from cell membrane to the nucleus. Cell.2003;113(6):685-700.
[37]Zheng R,Xiong Q,Zuo B,etal.Using RNA intere]ference to identify rhe different roles of SMAD2 and SMAD3 in NIH/3T3 fibroblast cells [J].Cell Biochem Funct,2008,26(5):548-556.
[38]陈伟,付小兵,王海滨等.增生性瘢痕形成和成熟过程中转化生长因子β及下游信号分子的基因表达变化.中华实验外科杂志,2005,22(6)：740-742.
[39]Whitman M.Signal transduction,feedback from inhibitory SMADs[J].Nature,1997,389: 549-551.
[40]Kolb M,Margetts PJ,Galt T,etal. Transient transgene expession of decorin in the lung reduces the fibrotic response to blemycin [J].Am J Respir Crit Care Med 2001,163(3):770-777.
[41]Lin RY,Sullivan KM,Argenta PA,etal.Exogenous transforming growth factor-beta amolifies its own expression and induces scar formation in amodel of human fetal skin repair[J]. AnnSurg,1955,222:146-454.
[42]董祥林,马少林.转化生长因子β在纤维化疾病中的研究与应用[J].中国临床康复.2004,8(35)：8050-8051.
[1]Asherman JG. Amenorrhoea traumatica (atretica) [J]. J Obstet Gynaecol Br Emp,1948, 55(1):23-30.
[2]Yu D, Wong YM, Cheong Y, et al. Asherman syndrome:one century later[J]. Fertil Steril, 2008,89(4):759-779.
[3]罗丽兰.不孕与不育[M].北京：人民卫生出版社,2009.241-242.
[4]Lonnroth K, Raviglione M. Global epidemiology of tuberculosis:prospects for control[J]. Semin Respir Crit Care Med 2008;29:481-491.
[5]李敏.王蔼明,商微,等.不同程度宫腔粘连相关影响因素及临床特征研究[J].人民军医.55(12)：1199-1200.
[6]Friedler S, Margalioth EJ, Kafka I, et al.Incidence of post-abortion intrauterine adhesions evaluated by hysteroscopy--aprospective study[J]. Hum Reprod,1993,8(3):442-444.
[7]Allnany H.Intrauterine adhesions[J].Acta Obstet Gynecol Scand.2001,80(11):986-993.
[8]Taskin O, Sadik S, Onoglu A, et al. Role of endometrial supression on the frequency of intrauterine adhesions after resectoscopic surgery[J].J Am Assoc Gynecol Laparosc,2000, 7(3):351-354.
[9]康美花,田春芳.宫腔粘连的临床研究进展[J].医学综述.2011,17(9)：1350-1353.
[10]韩义娜,任琛琛,申爱荣等.VEGF在宫腔粘连患者子宫内膜中的表达及与IL-18、TNF-α的关系[J].中国妇幼保健,2011,26(29)：4497-4499.
[11]雷琳,郑永才,陈志华.药物流产后出血的病理及相关因素分析[J].中国优生与遗传杂志,2004,12(3)：127-128.
[12]Caroline EG，David H.Generating receptive endomertrium in Asherman's syndrome[J].J Hum Reprod Sci,2011,4(1):49-52.
[13]Taylor E, Gomel V. The uterus and fertility[J]. Fertil Steril 2008;89:1-16.
[14]Berman JM.Intrauterine adhesions[J].Semin Reprod Med 2008;26:349-355.
[15]Nasr AT,A1-Inany HG,Thabet SM,etal.A clinicohysteroscopic scoring system of intrauterine adhesions[J].Gynecol Obstet Invest,2000,50(3):178-181.
[16]Sohail S.Uterine sonomorphology of Asherman syndrome on trans-vaginal ultrasound [J]. Pak J Med Sci,2005,21:451-454.
[17]Salle B,Gaucherand P,Hilaire PS,etal.Transvaginal sonohysterographic evaluation of intrauterine adhesion [J].J Clin Ultrasound,1999,27:131-134.
[18]蒋贤辉,赵博文,余婵,三维经阴道超声诊断宫腔粘连的临床应用[J].浙江医学,2011,33(3)：434-435.
[19]Cosmi E,Saccardi C,Litta P,etal.Transvaginal ultra-sound and sonohysterography for assessment of postpartum residual trophoblastic tissue[J].Int J Gynaecol Obstet,2010,110(3): 262-264.
[20]Soares SR,Barbosa dos Reis MM,Camargos AF.Diagnostic accura-cy of sonohysterography, transvaginal sonography,and hyste rosal-pingography in patients with uterine cavity diseases [J].Fertil Ster-Il,2000,73(2):406-411.
[21]夏恩兰.妇科内镜学[M].北京.人民卫生出版社,2001：104-107.
[22]Robinson J K,Colimon L M,Saacson K B.etal.Postoperative adhesiolysis therapy for intrauterine adhesions (Asherman's syndrome)[J].Fertil Steril,2008,90(2):409-414.
[23]Thomson A J,Abbott J A,Deans R,etal.The management of intrauterine synechiae[J].Curr Opin Obstet Gynecol,2009,21(4):335-341.
[24]张琳.子宫输卵管造影的临床进展和现状分析[J].中国实用医药,2011,6(7)：68-69.
[25]Sharma J B,Roy K K,Pushparaj M, etal. Genital tuberculosis:an important cause of Asherman's syndrome in India [J]. Arch Gyne-col Obstet,2008,277(1):37-41.
[26]Deans R,Abbott J.Review of intrauterine adhesions[J].J Minim Invasive Gynecol,2010, 17(5),555-569.
[27]Salamonsen,L.A.Tissue injury and repair in the female human reproductive tract[J]. Reproduction,2003.125(3):301-311.
[28]乐杰.妇产科学[M].7版.北京：人民卫生出版社,2008：6.
[29]Garry R,Hart R,Karthigasu KA,etal.Structural changes in endometrial basal glands during menstruation[J].BJOG,2010,117:1175-1185.
[30]Haruchika Masuda,Christoph Kalka,Tomono Takahashi etal.Estrogen-mediated endothelial progenitor cell biology and kinetics for physiological postnatal vasculogenesis[J]. Circ Res. 2007,101:598-606.
[31]Larson BJ, Longaker MT, Lorenz HP. Scarless fetal wound healing:a basic science review[J]. Plast Reconstr Surg.2010,126(4):1172-1180.
[32]Padykula HA. Regeneration in the primate uterus:the role of stem cells[J]. Ann N Y Acad Sci 1991;622:47-56.
[33]Chan, R.W. and C.E. Gargett, Identification of label-retaining cells in mouse endometrium[J]. Stem Cells,2006.24(6):1529-1538.
[34]Amer MI, Abd-EL-Maeboud KH. Anmion graft following hysteroscopic lysis of intrauterine adhesions[J] J ObstetGynaecol Res,2006,32 (6):559-566.
[35]段华.微创妇科全真手术[M].北京.江苏科学技术出版社,2008：102.
[36]夏恩兰.宫腔镜并发症防治的现代观点[J].国际妇产科学杂志.2008,35(5)：387-390.
[37]Leuschner H,Riedel HH,Anders M.Hysteroscopic survey from 1994 to 1996 in the eastem part of Gemany[J].J Am Assoc Gynecol Laparosc,1997,4(4Suppl):S28.
[38]Yasmin H,Nasir A,Noorani K J.Hysteroscopic management of Asherman's syndrome[J].J Pak Med Assoc,2007,57(11):553-555.
[39]Vesce F, Jorizzo G, Bianciotto A, et a.l Use of the copper intrauterine device in themanagement of secondary amen-orrhea[J].FertilSteri,l 2000,73:162-165.
[40]AlInany H.Intrauterine adhesions[J].Acta Obstet Gynecol S cand,2001,80:986-993.
[41]王淑贞,主编.实用妇产科学[M].北京.人民卫生出版社,1987,568-569.
[42]南秀牌,韩丽晖,吴明辉.宫内节育器并发宫颈宫腔粘连17例临床分析[J].实用妇产科杂志,2003,19(6)：369-370.
[43]范懿隽,卫兵,张妤.中重度宫腔粘连分离术后预防再粘连的临床研究[J].安徽医科大学学报,2011,46(4)：374-375.
[44]Lin JC,Chen YO,Chang CC,etal.Novel adjunctive treatment for cervical adhesion with cros-type nelaton catheter; a preliminary report and literature rewiew[J].Taiwan J Obstet Gynecol,2007,46(1):38-42.
[45]柳洁.宫腔粘连分离术后两种抗宫腔再粘连方法预后分析[J].中国误诊学杂志,2011,11(18)：4322.
[46]Robinson JK, Colimon LMS, Isaacson KB. Postoperative adhesiolysis therapy for intrauterine adhesions (Asherman's syndrome)[J].Fertil Steril,2008,90(2):409.
[47]赵永红.徐颖.透明质酸钠凝胶预防剖宫产后宫腔粘连的临床应用[J].中国组织工程研究与临床康复.2011,15(12)：2217-2220.
[48]Dilege E,Codam H.Prevention of adhesion to prosthetic mesh in incisional velltral hernias:comparison of different barriers in an experimen-talmodel.Surg Techol Int,2005, 14(7):185-190.
[49]康庆芝.应用综合方法预防宫腔粘连分离术后粘连的疗效分析[J].中外医疗,2010,40(7)：69-70.
[50]Liu Y,Cheng JM,Duang H,etal.Employment of intrauterine fibrin sealant with water bag instead of intrauterine device after laparoscopy combined with hysteroscopy transcervical resection of septus[J].Medical Jourmal of Wuhan University,2007,28(3):376-378.
[51]赵福杰,李妍,王敏等.生物蛋白胶在宫腔镜下宫腔粘连分离术后预防再次粘连的价值[J].中国内镜杂志,2008,14(11)：1131-1135.
[52]聂桂香.医用几丁糖凝胶预防输卵管复通后的粘连[J].中国组织工程研究与临床康复,2011,15(29)：5413-5416.
[53]侯春林.几丁糖生物学结构性研究[J].中国修复重建外科杂志,1993,7(2)：115.
[54]刘鑫磊.几丁糖防治介入治疗输卵管复通后再粘连的临床研究[J].中国妇幼保健.2005,23：3139-3140.
[55]Akle CA, Adinlfi M, Welsh KI, et al. Immunogenicity of human amniotic epithelial cells after transplantation into volunteers. Lancet,1981,2(8254):1003-5.
[56]Amer MI, Abdel Maeboud KH. Amnion graft following hysteroscopic lysis of intrauterine adhesions [J]. J Obstet Gynaecol Res,2006,32(6):559.
[57]Amer MI, Elmaeboud KH, Abdelfatah I,etal.Human amnion as a temporary biologic barrier after hysteroscopiclysis of severe intrauterine adhesions:pilot study [J] J Minim Invasive Gynecol,2010,17(5):605-611.
[58]彭雪冰,夏恩兰.羊膜宫腔内植入+人工周期治疗中、重度宫腔粘连的安全性及有效性[J].生殖与避孕.2012,32(12)：857-860.
[59]T seng SCG, LiD-Q,Ma X.Down-regulation of TGF-β1,β2,β3 and TGG-βreceptor II expression in human corneal broblasts by amniotic membrane[J]. Invest Ophthalmol Vis Sci 1998,39:428.
[60]Pabuccu R, Onalan G, Kaya C et al. Efficiency and pregnancy outcome of serial intrauterine device guided hysteroscopic adhesiolysis of intrauterine synechiae[J]. Fertil Steril,2008, 90(5):1973.
[61]牟晓玲.戊酸雌二醇在宫腔粘连中的治疗作用[J].中国妇幼保健.2010,25(9)：1274-1275.
[62]刘玉环,赵玉婷,蒋东桥等.大剂量雌激素对中重度宫腔粘连预后的影响[J].山东医药,2012,52(12)：14-16.
[63]Zinger M, Liu JH, Thomas MA. Successful use of vaginal sildenafil citrate in two infertility patients with Asherman's syndrome[J]. J Women's Health,2006,15(4):442.
[64]余世强,吴文清,李江等.通络补肾法合人工周期防治重度宫腔粘连术后再粘连临床研究[J].新中医.2011,43(11)：46-47.
[65]孙永忠.益肾活血调冲汤治疗宫腔粘连性不孕50例[J].山东中医杂志,2010,29(3)：167-168.
[66]Ju S,Teng GJ,Lu H, In vivo differentiation of magnetically labeled mesenchymal stemcells into hepatocytes for celltherapy to repair damaged liver [J].In vest Radiol.2010,45(10): 625-633.
[67]Diep CQ, Ma D, Deo RC, et al. Identification of adult nephron progenitors capable of kidney regeneration inzebrafish.Nature.2011.470(7332):95-100.
[68]赵潇丹.小鼠骨髓间充盾干细胞对子宫内膜损伤修复的初步研究[D].郑州.郑州大学,21.