血管内皮生长因子在子宫内膜异位症发病中的作用

目的探讨血管内皮生长因子(vascularendothelialgrowthfactor,VEGF)在子宫内膜异位症(endometriosis,EM)发病中的作用。方法应用免疫组织化学方法并结合图像分析技术。结果正常子宫内膜和EM在位内膜腺上皮细胞的VEGF随月经周期呈现规律性变化,分泌期腺上皮VEGF蛋白表达量显著高于增殖期(P<0.05)。在增殖期,EM在位子宫内膜腺上皮VEGF的表达与正常子宫内膜相比无明显差别,但在分泌期,EM在位子宫内膜腺上皮细胞中VEGF的表达强度明显高于正常子宫内膜(P<0.01)。EM在位内膜腺上皮的VEGF含量显著高于同组卵巢子宫内膜异位囊肿的异位腺上皮(P<0.01)。结论表明VEGF的表达异常与EM的发病有关。     

VEGF-165在异位、在位和正常子宫内膜中的表达

目的观察血管内皮生长因子-165(VEGF-165)在异位、在位及正常子宫内膜中表达的特点,探讨其与子宫内膜异位症(内异症)的关系.方法应用免疫组化LSAB法和图像分析,检测VEGF-165蛋白在卵巢子宫内膜异位囊肿患者异位内膜26例、在位子宫内膜15例及正常子宫内膜20例中的表达特点及其阳性细胞的分布规律.结果VEGF-165在正常及异位子宫内膜腺上皮和基质细胞均有不同程度的表达,其中异位内膜组织中呈高表达状态,与正常子宫内膜和内异症在位内膜相比有明显差异(P＜0.05);而VEGF-165于内异症在位内膜表达虽高于正常子宫内膜,但无统计学差异.结论VEGF-165在异位内膜组织中过度表达,提示其在子宫内膜异位症发病中起重要作用.     

子宫内膜异位症模型大鼠子宫内膜雌、孕激素受体表达的变化

利用大鼠子宫内膜异位症 (内异症 )动物模型 ,采用逆转录聚合酶链反应 (RT PCR)技术 ,检测子宫内膜雌激素受体 (ER)和孕激素受体 (PR)mRNAs的表达 ,探讨内异症的发病机理及激素治疗的可能性。结果表明 ,内异症模型组大鼠异位内膜ER、PRmRNAs的表达低于在位内膜及对照组正常子宫内膜 ,与后两者比较差异有显著性意义(P <0 0 1 ) ;而模型组在位内膜ER、PRmRNAs的表达与正常对照组比较差异无显著性意义。内异症模型组异位内膜ER PRmRNA比值大于在位内膜及正常子宫内膜ER PRmRNA比值 (P <0 0 1 )。提示内异症大鼠异位内膜ERmRNA表达的降低在内异症的发生与发展中起着一定的作用     

血管内皮生长因子及其受体在子宫内膜异位症中的表达和意义

目的:研究血管内皮生长因子(Vascular endothelial growth factor,VEGF)及其受体(Vascular endothelial growth factor receptor1,VEGFR1)在子宫内膜异位症(内异症)患者子宫在位内膜、异位内膜及正常对照组内膜组织中的表达,探讨其在子宫内膜异位症中的作用机制.方法:采用免疫组织化学及Western blot方法检测34例异位症患者在位内膜、异位内膜(内异症组)及34例正常内膜(对照组)组织中VEGF及其受体VEGFR1蛋白的定位及表达.结果:异症组在位及异位子宫内膜组织腺上皮细胞及间质细胞中均有VEGF及VEGFR1蛋白表达,且均高于同期对照组内膜,差异有统计学意义;对照组分泌期内膜VEGF及VEGFR1蛋白表达高于增生期,呈现周期性变化,而内异症组在位及异位内膜VEGF及VEGFR1蛋白表达失去周期性变化,分泌期与增生期均高表达,差异无统计学意义.Western blot检测结果与免疫组化结果一致.结论:内异症患者在位及异位内膜组织中VEGF、VEGFR1蛋白高表达可能与内异症的发生发展有关.     

GnRHⅡ蛋白在子宫内膜异位症患者中的表达及意义

目的：检测GnRHⅡ蛋白在子宫内膜异位症患者异位子宫内膜、在位子宫内膜和正常子宫内膜中的表达情况,同时分析其表达是否与子宫内膜月经周期有关。方法：采用免疫组织化学SP法检测GnRHⅡ蛋白在异位内膜、在位内膜及正常子宫内膜组织中的表达情况,并分析和比较其表达是否有差异。结果：GnRHⅡ蛋白在子宫内膜异位症患者异位、在位子宫内膜及正常子宫内膜中均有表达,阳性表达定位于子宫内膜腺体及间质细胞的细胞质;GnRHⅡ蛋白在异位内膜、在位内膜及对照组正常内膜的表达依次增强,两两比较差异有统计学意义（P＜0.05）;GnRHⅡ蛋白在正常子宫内膜分泌期表达强于增生期（P＜0.05）,且以分泌早中期最强,显著强于增生期和分泌晚期（P＜0.01）,而异位组或在位组的分泌期与增生期比较,差异无统计学意义（P＞0.05）。结论：GnRHⅡ蛋白在子宫内膜异位症的发病中以及在人类月经生理方面可能起重要作用。     

内异症子宫内膜ER、PR基因表达的研究

目的/:v探讨子宫内膜异位症(内异症)子宫内膜雌激素受体(ER)、孕激素受体(PR)基因表达在内异症发病中的作用。方法:利用大鼠内异症动物模型,采用逆转录聚合酶链反应(RT-PCR)技术,检测子宫内膜ER和PRmRNAs的表达情况。结果:内异症模型组大鼠异位内膜ER、PRmRNAs的表达显著低于在位内膜及对照组正常子宫内膜(P＜0.01);而模型组在位内膜ER、PRmRNAs的表达与正常对照组比较差异无显著(P＞0.05)。内异症模型组异位内膜ER/PRmRNA比值大于在位内膜及正常子宫内膜ER/PRmRNA比值(P＜0.01)。结论:内异症大鼠异位内膜ERmRNA表达的相对增高在内异症的发生与发展中起着一定的作用。     

子宫腺肌症雌激素受体、孕激素受体与bcl-2的表达

目的 探讨雌激素受体（ER）、孕激素受体（PR）和bcl-2在子宫腺肌症中异位和在位内膜的表达及意义。方法 用免疫组化EnVision法检测40例子宫腺肌症在位子宫内膜和肌间异位内膜ER、PR和bcl-2的表达情况。结果 在位和异位子宫内膜组织中均有ER、PR和bcl-2的阳性表达。其中腺上皮阳性表达率高于间质（P〈0．05），且异位内膜的腺上皮bcl-2阳性表达率高于在位组织（P〈0．05）；ER和PR的表达两者差异无显著性（P〉0．05）。异位内膜腺体ER、PR与bcl-2表达具有相关性（P〈0．01）。结论 子宫腺肌症异位和在位子宫内膜组织中均有ER、PR和bcl-2的阳性表达，可能与子宫腺肌症的发生、发展有关。     

凋亡相关蛋白Bcl-2/Bax与子宫内膜异位症的相关性研究

目的研究子宫内膜异位症(内异症)及子宫腺肌症患者在位及异位内膜组织中细胞凋亡相关蛋白Bcl-2、Bax表达及其凋亡率比较。方法采用免疫组化法检测各组织标本中Bcl-2、Bax的表达,流式细胞仪测定各组织的细胞凋亡率。结果(1)在正常和正位内膜组织中,Bcl-2或Bax表达相同(P>0.05),具有明显周期性变化,均为增生期高于分泌期(P<0.05);(2)子宫腺肌病和腹壁异位内膜中,Bcl-2或Bax均持续表达,无周期性变化(P>0.05);(3)卵巢内异症的异位内膜,Bcl-2和Bax极少表达;(4)流式结果显示正常子宫内膜、在位内膜凋亡率与异位内膜组织凋亡率有显著性差异(P<0.05)。结论①Bcl-2或Bax在正常和在位子宫内膜的周期性表达,提示它们可能参与月经周期调节;②子宫腺肌病及腹壁异位内膜腺上皮细胞Bcl-2持续存在,使之得以长期增殖而发病;③卵巢内异症极少表达Bcl-2可能是促成细胞凋亡形成,引起巧克力囊肿的原因。     

Bcl-2蛋白、Ki-67抗原、雌激素受体及孕激素受体在子宫腺肌病子宫内膜中的表达

目的 检测与分析细胞凋亡抑制因子(Bcl-2蛋白)、细胞核相关抗原(Ki-67抗原)、雌激素受体(ER)、孕激素受体(PR)在子宫腺肌病(AM)在位内膜、异位内膜和正常子宫内膜中的表达情况及相关性,探讨其在AM发病机制中的作用.方法 采用免疫组织化学PicTureTM二步法检测40例AM在位内膜、异位内膜及38例正常子宫内膜中Bcl-2蛋白、Ki-67抗原、ER、PR的表达情况.采用Spearman等级相关分析这些因素间表达的相关性.结果 (1)Bcl-2蛋白、Ki-67抗原在AM在位内膜和正常子宫内膜中表达有周期性变化,增生期高于分泌期(P＜0.05);而在AM异位内膜中表达无明显周期性变化.(2)Bcl-2蛋白、Ki-67抗原在3种内膜的表达情况:AM异位内膜＞AM在位内膜＞正常子宫内膜,差异有统计学意义(P＜0.05).(3)AM在位内膜、正常子宫内膜中Bcl-2蛋白、Ki-67抗原的表达与ER、PR的表达呈正相关(P＜0.05);AM异位内膜中Bcl-2蛋白、Ki-67抗原的表达与ER、PR的表达无相关.结论 AM在位、异位内膜中Bcl-2蛋白、Ki-67抗原的异常表达可能与AM的发生、发展有关.     

PTEN与Beclin1在子宫内膜异位症的表达和临床意义

目的 考察PTEN与Beclin1在子宫内膜异位症的表达和临床意义.方法 采用免疫组化法测定40例子宫内膜异位症患者在位内膜、异位内膜和20例正常对照的PTEN与Beclin1表达水平.并考察不同病理资料与两者表达水平关联.结果 正常对照、在位内膜、异位内膜三者的PTEN与Beclin1表达水平均逐渐下降(P＜0.05).其中PTEN在正常对照、在位内膜和异位内膜的增生期、分泌期表达均无显著差异(P＞0.05).但Ⅲ-Ⅳ期表达率低于Ⅰ-Ⅱ期患者(P＜0.05).Beclin1在在位内膜和异位内膜的增生期、分泌期表达均无显著差异(P＞0.05),却在正常对照中具有显著差异(P＜0.05),同时Ⅲ-Ⅳ期表达率低于Ⅰ-Ⅱ期患者(P＜0.05).PTEN与Beclin1在子宫内膜异位症组织中表达水平正相关.结论 PTEN与Beclin1的低表达与子宫内膜异位症的发生和发展相关,但其具体作用机制值得进一步深入研究.     

Roles of estrogen receptor α and β in the regulation of proliferation in endometrial carcinoma

Endometrial carcinoma (EC), an estrogen-dependent gynecological malignancy, is prevalent worldwide. Estrogen receptor α (ERα) and estrogen receptor β (ERβ) are two main estrogen receptor isoforms, which mediate estrogen-induced proliferation in EC. However, the dynamic changes of ERα and ERβ subtype expression and their functions on proliferation in EC remain elusive. In this study, we aimed to investigate the expression of ERα and ERβ in para-tumor eutopic endometrium, endometrial atypical hyperplasia and EC by immunohistochemistry and then analyse their clinical significance. Subsequently, Ishikawa cells with ERα or ERβ knockdown by lentivirus transfection were used to explore the relationship between ERα/ERβ and cell proliferation, and preliminarily evaluate whether metformin’s inhibitory effect on estrogen-induced cell proliferation was mediated by ERα and ERβ. We found that the expression of ERα and ERβ were markedly changed in endometrial hyperplasia and EC compared with that in para-tumor eutopic endometrium and exhibited different expression trends. Through further analysis, we discovered that ERα presented higher expression in endometrial atypical hyperplasia and early stage of EC than that in para-tumor eutopic endometrium, while the expression of ERβ gradually decreased from para-tumor eutopic endometrium to EC. Additionally, the cell cycle-related protein, CyclinD1 was gradually increased but p21 decreased. Furthermore, knockdown of ERα and ERβ severally in Ishikawa cells either inhibited or promoted estrogen-induced cell proliferation through regulating CyclinD1 and p21 expression. Meanwhile, the inhibitory effect of metformin on estrogen-induced cell proliferation was respectively blunted or partly reversed by knockdown of ERα or ERβ. Altogether, ERα and ERβ have different expression patterns in the progression of EC either facilitating or suppressing cell proliferation through regulating the expression of CyclinD1 and p21 in EC cells, and may also mediate the inhibitory effect of metformin on estrogen-induced EC cells proliferation.     

子宫内膜及异位灶趋化因子受体转录在子宫内膜异位症发病中的作用

目的：探讨子宫内膜异位症患者在位内膜及异位灶18种趋化因子受体的转录特征，以揭示趋化因子受体及其配体在子宫内膜异位症发生发展中的作用。方法：以正常子宫内膜为对照，半定量RT-PCR检测子宫内膜异位症患者在位内膜及异位灶18种趋化因子受体mRNA的表达水平，并比较其差异。结果：与正常子宫内膜相比，子宫内膜异位症患者在位子宫内膜CCR6、CCR8、CCR9、CX3CR1表达明显升高（P＜0．05）。与在位内膜相比，异位灶CCR4、CCR8、CCR9、CXCR1表达显著升高（P＜0．05）。结论：在位子宫内膜CCR6、CCR8、CCR9、CX3CR1高表达，可能参与子宫内膜异位症的发生；异位灶CCR4、CCR8、CCR9、CXCR1高表达，可能参与子宫内膜异位症的进一步发展。     

Differential expression and localization of de-novo synthesized endometriotic haptoglobin in endometrium and endometriotic lesions

Endometriosis protein-I (ENDO-I) mRNA expression and protein localization were evaluated using in-situ hybridization and immunohistochemistry in endometriotic lesions and eutopic endometrium from women with endometriosis, and in eutopic endometrium from women without endometriosis (controls). When present, ENDO-I mRNA and protein were observed in the functionalis zone of endometrial stroma and the stroma of endometriotic lesions. Expression and localization differences were scored and statistically analysed. During the secretory stage, ENDO-I mRNA expression by endometriotic lesions and eutopic endometrium from women with disease was significantly greater than ENDO-I mRNA expression by proliferative stage eutopic endometrium from women with disease or eutopic endometrium from controls, regardless of cycle stage (P < 0.001). More ENDO-I protein was localized in endometriotic lesions and eutopic endometrium from women with disease than in eutopic endometrium from controls, regardless of cycle stage (P < 0.001). Differential expression and localization of ENDO-I may help develop minimally invasive diagnostic strategies for endometriosis. Further, as ENDO-I shares nucleotide sequence and amino acid sequence with hepatic haptoglobin-which in certain disease states is immunosuppressive and angiogenic-differences in ENDO-I expression and localization in the peritoneal cavity may contribute to the pathogenesis of endometriosis and/or facilitate development of unprecedented diagnostic or therapeutic approaches for management of this enigmatic disease.     

Vascular endothelial growth factor A and C gene expression in endometriosis

Angiogenesis is essential for the pathogenesis of endometriosis. Gene expression levels of vascular endothelial growth factor (VEGF) A and C in 10 eutopic endometrial, 23 normal peritoneal, and 62 endometriotic tissues surgically obtained from 47 women with endometriosis (group 2) were compared with those in 12 control eutopic endometrial and 9 normal peritoneal tissues from 15 women without endometriosis (group 1). VEGF-A mRNA expression levels in eutopic endometrium of group 2 were higher than those of group 1 throughout the menstrual cycle (P <0.01) and increased in the secretory phase. VEGF-A gene expression in peritoneal endometriotic lesion was statistically higher than that in normal peritoneum (P <0.01) and similar to that in eutopic endometrium of group 2. In contrast, gene expression levels of VEGF-C were relatively lower than those of VEGF-A in each lesion, and no cyclic variation was found. VEGF-A and C mRNA expression levels were significantly higher in ovarian endometriomas >6 cm in size than in those <6 cm in size. Immunohistochemical expression of VEGF-A and C was detected in the cytoplasm of glandular epithelial and stromal cells of ovarian endometrioma. These results suggest that endometriosis may arise from eutopic endometrium with higher levels of angiogenic activity possibly induced by VEGF-A in women with endometriosis. Moreover, VEGF-C as well as VEGF-A may be involved in the pathogenesis of ovarian endometrioma.     

Bcl-2蛋白、Ki-67抗原、雌激素受体及孕激素受体在子宫腺肌病子宫内膜中的表达

目的检测与分析细胞凋亡抑制因子(Bcl-2蛋白)、细胞核相关抗原(Ki-67抗原)、雌激素受体(ER)、孕激素受体(PR)在子宫腺肌病(AM)在位内膜、异位内膜和正常子宫内膜中的表达情况及相关性,探讨其在AM发病机制中的作用。方法采用免疫组织化学PicTureTM二步法检测40例AM在位内膜、异位内膜及38例正常子宫内膜中Bcl-2蛋白、Ki-67抗原、ER、PR的表达情况。采用Spearman等级相关分析这些因素间表达的相关性。结果(1)Bcl-2蛋白、Ki-67抗原在AM在位内膜和正常子宫内膜中表达有周期性变化,增生期高于分泌期(P<0.05);而在AM异位内膜中表达无明显周期性变化。(2)Bcl-2蛋白、Ki-67抗原在3种内膜的表达情况:AM异位内膜>AM在位内膜>正常子宫内膜,差异有统计学意义(P<0.05)。(3)AM在位内膜、正常子宫内膜中Bcl-2蛋白、Ki-67抗原的表达与ER、PR的表达呈正相关(P<0.05);AM异位内膜中Bcl-2蛋白、Ki-67抗原的表达与ER、PR的表达无相关。结论AM在位、异位内膜中Bcl-2蛋白、Ki-67抗原的异常表达可能与AM的发生、发展有关。