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。     

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.     

血管生成素-2和内皮抑素在子宫内膜异位症中的高表达

目的 探讨血管生成素-2（ANG-2）和内皮抑素（ENS）在子宫内膜异位症发生发展中的作用。方法 卵巢子宫内膜异位症病人25例，24例无内膜病变者为对照组。留取子宫内膜，用免疫组化染色法检测ANG -2和ENS在子宫内膜中的表达，用酶联免疫吸附测定法检测腹腔液中ANG -2和ENS的蛋白含量。结果ANG -2在位子宫内膜组织中的阳性表达率显著高于异位内膜和对照组，异位内膜中阳性表达率显著高于对照组；ENS在异位内膜组织中的表达明显高于在位内膜和对照组，在位内膜明显高于对照组；ANG-2及ENS表达强度在子宫内膜异位症Ⅰ、Ⅱ期与Ⅲ、Ⅳ比较无显著差异。异位组腹腔液的ANG-2、ENS含量和ANG-2/ENS 比值均显著高于对照组。结论ANG-2和ENS在子宫内膜异位症血管生成中起到重要的作用，参与调节异位病灶的发生和进展。     

血管内皮生长因子对子宫内膜异位症大鼠缺氧及炎症微环境的作用机制

目的：探讨血管内皮生长因子（VEGF）对子宫内膜异位症（EMs）大鼠缺氧以及炎症微环境的作用机制。方法：采用自体子宫内膜移植法构建大鼠EMs模型。动物实验分为假手术组、模型组、对照组、实验组。其中假手术组大鼠在造模过程中仅进行子宫内膜截取,不进行内膜移植,每日尾静脉注射VEGF-siRNA-NC,模型组、对照组和实验组大鼠在造模后每日尾静脉注射VEGF-siRNA-NC,实验组大鼠每日尾静脉注射VEGF-siRNA。处死大鼠后检测各组大鼠异位内膜的体积;ELISA检测各组大鼠血清中TNF-α和IL-1β含量。高通量测序确定RNA干扰后的靶点基因。Western blot检测样本组织中VEGF、缺氧诱导因子-1α(HIF-1α)和髓过氧化物酶（MPO）的表达。结果：高通量测序结果显示HIF-1α、MPO为干扰VEGF的RNA后的靶点基因。与假手术组相比,模型组、对照组、实验组大鼠的异位内膜体积、血清中TNF-α和IL-1β含量和样本中VEGF、HIF-1α、MPO表达均明显升高;与对照组相比,实验组大鼠的异位内膜体积、血清中TNF-α和IL-1β含量和样本中VEGF、HIF-1α、MPO...     

子宫内膜干细胞学说在子宫内膜异位症中的作用及研究进展

BACKGROUND:Pathogenesis of endometriosis involves many factors that ultimately lead to the emergence of endometrial glands and stroma outside the uterine cavity. OBJECTIVE:To review the research progress in the theory of endometrial stem cells, and to provide suggestions for the pathogenesis and treatment of endometriosis. METHODS:VIP database and PubMed database were retrieved for articles addressing endometriosis stem cell theory, including original research, experimental analysis, case analysis and review, published from January 2005 to October 2015. Keywords were "endometriosis, stem cells" in Chinese and English, respectively. After removal of repetitive articles, 48 articles were included for final analysis. RESULTS AND CONCLUSION:Endometrial stem/progenitor cells may exist in the endometrium, and these cells and bone marrow stem cells are speculated to be involved in the occurrence of endometriosis. Therefore, treatment of endometriosis is targeted to endometrial stem/progenitor cells and abnormal regulation on signal transduction pathway, which provides new insight into the mechanism of action and treatment of endometriosis.     

血管生成素-2和内皮抑素在子宫内膜异位症患者异位、在位内膜组织中的表达及意义

目的探讨血管生成素-2和内皮抑素在子宫内膜异位症血管生成中的作用。方法采用免疫组化法检测25例内异症患者在位内膜和异位内膜中血管生成素-2及内皮抑素的蛋白含量并与对照组相比较。结果Ang-2的表达在位内膜高于异位内膜高于对照组,两两比较,差异显著。ENS的表达异位内膜高于在位内膜高于对照咱,两两比较,差异显著。Ang-2在EM组和对照组的分泌期表达均高于增生期,有统计学意义。ENS在EM组和对照组的表达,分泌期和增生期无统计学差异。Ang-2表达强度与r-AFS内异症分期无明显相关性。Ⅲ～Ⅳ期患者在位内膜中ENS表达量高于Ⅰ～Ⅱ期患者,差异有统计学意义。结论1.在位内膜可能具有更强的血管生成活性,而种植成功的内膜中具有更强的血管抑制能力以限制异位病灶的扩散。2.分泌期内膜更容易在异位种植,血管生成的调控可能与激素水平有关。     

抗血管内皮生长因子抑制裸鼠异位子宫内膜生长

目的构建子宫内膜异位种植裸鼠模型,在此基础上研究抗血管内皮生长因子(VEGF)抗体在治疗中的作用及机制。方法将人子宫内膜组织种植到裸鼠体内,抗VEGF抗体作用于种植灶,进行分组对照研究。用TUNEL标记法检测细胞凋亡、PCNA检测细胞增殖和微血管密度(MVD)。结果实验组细胞凋亡强度明显高于对照组,细胞增殖强度在各组间无明显差异。实验组人源性MVD和鼠源性MVD都明显低于对照组(P<0.05)。结论抗VEGF抗体可能是通过促进子宫内膜细胞和血管内皮细胞的凋亡、抑制血管生成,继而抑制内膜异位种植生长,而对细胞增殖无明显抑制作用。     

胎盘生长因子(PLGF)及其受体血管内皮生长因子受体-1(VEGFR-1)在子宫内膜异位症中的表达及意义

目的探讨胎盘生长因子(PLGF)及其受体血管内皮生长因子受体-1(VEGFR-1)与子宫内膜异位症(endom etriosis,EMS)发病的相关性。方法用免疫组织化学染色法检测28例子宫内膜异位症患者的在位子宫内膜和异位子宫内膜(增生期、分泌期各14例),以及28例正常子宫内膜(增生期15例,分泌期13例)中PLGF及其受体VEGFR-1的表达。结果PLGF、VEGFR-1在各组内膜中均有表达,分泌期表达高于增生期,有显著差异。EMS的异位子宫内膜中的表达显著高于其在位子宫内膜和正常子宫内膜;EMS的在位子宫内膜和正常子宫内膜之间比较无明显差异。结论PLGF、VEGFR-1可能参与子宫内膜异位症的发病过程。     

血管生成素-2和内皮抑素在子宫内膜异位症患者血清和腹腔液中的表达及意义

目的探讨血管生成素-2和内皮抑素在子宫内膜异位症血管生成中的作用。方法采用酶联免疫吸附测定法检测30例内异症患者腹腔液和血清中血管生成素-2及内皮抑素的蛋白含量并与对照组相比较。结果内异症组血清和腹腔液中Ang-2、ENS含量及Ang-2／ENS比值均高于对照组,P〈0．05,差异有统计学意义。结论1．盆腹腔的血管生成活性可能强于远处组织和器官,利于逆流入腹腔的子宫内膜碎片的种植。2．内异症的血管生成取决于多种因子间的相互协调,当血管生成的动态平衡被打破,正性血管调节因子Ang-2在总体上处于主导地位时,就启动了新生血管的生成     

子宫内膜异位症中miR-556-3p的异常表达及其与血管内皮生长因子的关系

目的探索micro RNA-556-3p（mi R-556-3p）在子宫内膜异位症中的表达模式及其与血管内皮生长因子（vascular endothelium growth factor,VEGF）的关系。方法子宫内膜异位症患者15例作为研究组,分别收集在位内膜、卵巢异位内膜及腹膜异位内膜;无子宫内膜病变的妇女16例,收集子宫内膜组织作为对照组。Taqman real-time PCR检测上述组织中mi R-556-3p的水平,Western Blot法检测组织中VEGF蛋白含量,并分析mi R-556-3p与VEGF表达水平之间的相关性。结果与对照组相比较,内异症患者在位内膜及腹膜异位病灶中mi R-556-3p水平显著降低（P〈0.001）,而VEGF含量在内异症在位内膜、卵巢异位囊肿或腹膜异位内膜中均显著升高（P值分别为〈0.001、0.02、〈0.001）;与内异症组在位内膜相比较,卵巢异位病灶中mi R-556-3p显著升高（P〈0.001）,腹膜异位病灶中mi R-556-3p的表达量则显著降低（P〈0.001）,而VEGF显著升高（P〈0.001）;异位症组在位内膜及腹膜异位病灶中mi R-556-3p与VEGF蛋白的表达量呈显著负相关（r值分别为-1.026、-1.819,P值分别为0.01、0.04）。结论内膜组织中mi R-556-3p表达异常可能导致VEGF蛋白表达失调,参与子宫内膜异位症的发生发展。     

Effect of GnRH analogues on apoptosis and release of interleukin-1beta and vascular endothelial growth factor in endometrial cell cultures from patients with endometriosis

BACKGROUND: The aim of the present study was to evaluate the effect of GnRH analogues on the in-vitro eutopic endometrial cell apoptosis and release of interleukin-1beta (IL-1beta) and vascular endothelial growth factor (VEGF). METHODS: Biopsy specimens of eutopic endometrium obtained from 16 women with untreated endometriosis and 14 controls were studied. Apoptosis, IL-1beta and VEGF release were evaluated in epithelial endometrial cell cultures after incubation with leuprolide acetate (LA) as GnRH agonist, antide as GnRH antagonist, and a combination of both. The percentage of apoptotic cells was evaluated by the acridine orange-ethidium bromide technique, and IL-1beta and VEGF concentrations were assessed by using commercial enzyme-linked immunosorbent assay (ELISA) kits. RESULTS: We found that LA (100 ng/ml) enhanced apoptosis in endometrial cell cultures from endometriosis patients and controls and this effect was reversed by antide at 10(-7) mol/l. IL-1beta and VEGF release was downregulated by LA in cultures from controls and endometriosis patients. The addition of antide 10(-7) mol/l reversed this inhibition. Endometrial cultures treated with antide at 10(-7) mol/l did not show any significant effects compared with basal conditions. CONCLUSIONS: GnRH agonists appear to have a direct effect in endometrial cells cultures, by enhancing the percentage of apoptotic cells and decreasing the release of pro-mitogenic cytokines such as IL-1beta and VEGF.     

Levels of vascular endothelial growth factor (VEGF) in serum of patients with endometriosis

BACKGROUND: Elevated concentrations of vascular endothelial growth factor (VEGF) have been detected in the peritoneal fluid of patients with endometriosis. Furthermore, it was postulated that VEGF is involved in the development of endometriotic lesions. The present study is aimed at determining whether high levels of VEGF could also be found in the serum of patients with endometriosis. METHODS: VEGF levels were measured by enzyme-linked immunosorbent assay (ELISA) in serum from 131 subjects with surgically confirmed endometriosis and 146 controls with no clinical evidence of the disease or detectable endometriotic lesions at the time of surgical examination. Parameters such as demographics, personal habits, menstrual characteristics and clinical profile were collected from each subject included in this study. RESULTS: The mean VEGF levels were not significantly modulated in serum samples of cases compared with controls in a crude general linear model and in a model adjusted for possible confounders. VEGF serum levels did not correlate with the score, stage of endometriosis or the presence of benign gynaecological disorders. However, a correlation was found between circulating concentrations of VEGF and body mass index. CONCLUSION: Although VEGF seems to play a pivotal role locally in the implantation and development of endometriotic lesions, the disease is not associated with a significant modulation in the levels of circulating VEGF.     

类风湿关节炎患者抗血管内皮细胞抗体、血管内皮生长因子和白细胞介素-17的检测及意义

目的 通过对类风湿关节炎(RA)患者血清抗血管内皮细胞抗体(AECA)、血浆血管内皮生长因子(VEGF)和白细胞介素-17(IL-17)的检测,旨在探讨AECA、VEGF、IL-17在RA患者发病、病情进展中的相关性及其内在联系.方法 采用间接免疫荧光法(IIF)和双抗体夹心酶联免疫吸附试验(ELISA)法检测86例RA、45例骨关节炎(OA)、30例健康对照AECA的阳性率和VEGF、IL-17水平,VEGF、IL-17水平与红细胞沉降率(ESR)、超敏C反应蛋白(hs-CRP)、类风湿因子(RF)等指标进行相关性分析.结果 RA患者AECA阳性率为8.1%,高于OA患者的阳性率2.2%(t:2.133,P<0.05)和健康对照的阳性率0(t=2.562,P<0.05);RA活动期AECA阳性率为16.7%,高于RA缓解期的阳性率3.6%(t=2.105,P<0.05);RA患者血浆IL-17和VEGF水平显著高于OA组(t=2.02、t=2.106,P<0.05)和健康对照组(t=2.413、t=2.469,P<0.05);RA患者活动期血浆IL-17和VEGF水平明显高于RA缓解组(t=2.315、t=2.232,P<0.05)及健康对照组(t:2.985、t=2.753,P<0.01);RA缓解组与健康对照组无明显差异(t=1.475、t=1.326,P>0.05);RA患者AECA滴度、血浆IL-17、VEGF水平与ESR、hs-CRP、RF的指标呈正相关.结论 AECA、VEGF、IL-17三者与RA的发病、病情活动存在一定的关系,IL-17、VEGF水平变化及AECA的滴度可作为临床观察RA病情活动、判断疗效及预后等方面的参考指标.     

类风湿关节炎患者抗血管内皮细胞抗体、血管内皮生长因子和白细胞介素-17的检测及意义

目的通过对类风湿关节炎（RA）患者血清抗血管内皮细胞抗体（AECA）、血浆血管内皮生长因子（VEGF）和白细胞介素-17（IL-17）的检测,旨在探讨AECA、VEGF、IL-17在RA患者发病、病情进展中的相关性及其内在联系。方法采用间接免疫荧光法（IIF）和双抗体夹心酶联免疫吸附试验（ELISA）法检测86例RA、45例骨关节炎（OA）、30例健康对照AECA的阳性率和VEGF、IL-17水平,VEGF、IL-17水平与红细胞沉降率（ESR）、超敏C反应蛋白（hs．CRP）、类风湿因子（RF）等指标进行相关性分析。结果RA患者AECA阳性率为8．1％,高于OA患者的阳性率2．2％（t=2．133,P〈0．05）和健康对照的阳性率0（t=2．562,P〈0．05）;RA活动期AECA阳性率为16．7％,高于RA缓解期的阳性率3．6％（f=2．105,P〈0．05）;RA患者血浆IL-17和VEGF水平显著高于OA组（t=2．02、t=2．106,P〈0．05）和健康对照组（t=2．413、t=2．469,P〈n05）;RA患者活动期血浆IL—17和VEGF水平明显高于RA缓解组（t=2．315、t=2．232,P〈0．05）及健康对照组（仁2．985、t=2．753,P〈0．01）;RA缓解组与健康对照组无明显差异（t=1．475、t=1．326,P〉0．05）;RA患者AECA滴度、血浆IL-17、VEGF水平与ESR、hs—CRP、RF的指标呈正相关。结论AECA、VEGF、IL-17三者与RA的发病、病情活动存在-定的关系,IL-17、VEGF水平变化及AECA的滴度可作为临床观察RA病情活动、判断疗效及预后等方面的参考指标。     

类风湿关节炎患者抗血管内皮细胞抗体、血管内皮生长因子和白细胞介素-17的检测及意义

目的 通过对类风湿关节炎(RA)患者血清抗血管内皮细胞抗体(AECA)、血浆血管内皮生长因子(VEGF)和白细胞介素-17(IL-17)的检测,旨在探讨AECA、VEGF、IL-17在RA患者发病、病情进展中的相关性及其内在联系.方法 采用间接免疫荧光法(IIF)和双抗体夹心酶联免疫吸附试验(ELISA)法检测86例RA、45例骨关节炎(OA)、30例健康对照AECA的阳性率和VEGF、IL-17水平,VEGF、IL-17水平与红细胞沉降率(ESR)、超敏C反应蛋白(hs-CRP)、类风湿因子(RF)等指标进行相关性分析.结果 RA患者AECA阳性率为8.1%,高于OA患者的阳性率2.2%(t:2.133,P<0.05)和健康对照的阳性率0(t=2.562,P<0.05);RA活动期AECA阳性率为16.7%,高于RA缓解期的阳性率3.6%(t=2.105,P<0.05);RA患者血浆IL-17和VEGF水平显著高于OA组(t=2.02、t=2.106,P<0.05)和健康对照组(t=2.413、t=2.469,P<0.05);RA患者活动期血浆IL-17和VEGF水平明显高于RA缓解组(t=2.315、t=2.232,P<0.05)及健康对照组(t:2.985、t=2.753,P<0.01);RA缓解组与健康对照组无明显差异(t=1.475、t=1.326,P>0.05);RA患者AECA滴度、血浆IL-17、VEGF水平与ESR、hs-CRP、RF的指标呈正相关.结论 AECA、VEGF、IL-17三者与RA的发病、病情活动存在一定的关系,IL-17、VEGF水平变化及AECA的滴度可作为临床观察RA病情活动、判断疗效及预后等方面的参考指标.     

Circulating levels of interleukin-8 and vascular endothelial growth factor in patients with carotid stenosis

Interleukin (IL)-8 and vascular endothelial growth factor (VEGF) are important factors that induce the migration and proliferation of endothelial cells, increase the vascular permeability, and the modulate chemotaxis of monocytes. These molecules have been found in human atherosclerotic plaques. However, it is not clear whether the circulating levels of IL-8 and VEGF correlate with the extents of carotid stenosis. In this study, we investigated the relationship between circulating levels of IL-8 as well as VEGF and the extents of carotid stenosis. Sera from 41 patients with carotid stenosis were assessed for concentrations of IL-8 and VEGF by enzyme-linked immunosorbent assay. The degree of stenosis of extracranial carotid artery was calibrated by carotid B- mode ultrasonography. The serum concentration of IL-8 (r = -0.04733, p > 0.05) was not correlated with the degree of stenosis. However, the serum concentration of VEGF (r = 0.4974, p < 0.01) was significantly correlated with the degree of carotid stenosis. These findings suggest that increased serum level of VEGF might be a marker for higher degree of stenosis of extracranial carotid artery.     

Expression of vascular endothelial growth factor C and anti-angiogenesis therapy in endometriosis

Angiogenesis is an important pathogenesis of Endometriosis. Vascular endothelial growth factor C (VEGF-C) is one of the most important factor in the regulation of both normal and abnormal angiogenesis. Anti-angiogenic treatment of endometriosis is still in the exploratory stage. In this study, we investigate the relationship between VEGF-C and endometriosis, the therapeutic effects of Endostar in the rat endometriosis model. We then demonstrated that Immunohistochemical expression of VEGF-C was higher in endometriotic tissues than in control normal ovary tissues (P < 0.01) and higher in the endomertriosis grade III-IV than in endomertriosis grade I-II (P=0.013). In rat endometriosis model, we observed a significant reduction in the mean volume and weight of the endometriotic implants per rat in the treatment group as compared with the control group. By immunohistochemical evaluation, there was a significant reduction in VEGF-C expression after treatment in all areas examined. VEGF-C may be involved in the pathogenesis of endomertriosis by regulating the angiogenesis. Endostar has therapeutic effects of endometriosis lesions in the rat endometriosis model.