孕激素受体亚型在卵巢子宫内膜异位囊肿组织的表达

目的:探讨内异症治疗中“孕激素耐受”影响疗效的可能机制。方法:选取30例卵巢子宫内膜异位囊肿患者的巧克力囊肿组织,其中6例同时行子宫切除术患者的在位内膜组织和13例正常内膜组织,采用RT-PCR技术半定量检测子宫内膜异位症(EMs)组织中孕激素受体亚型hPR-A+B和hPR-B的基因表达。结果:巧克力囊肿组织中总PR和PR-BmRNA表达明显低于正常内膜组织和EMs患者在位内膜组织,差异有统计学意义;巧克力囊肿组织中PR-B/PR-A+BmRNA的比值低于正常子宫内膜组织,差异有统计学意义。结论:PR和PR-B/PR-A+BmRNA的比值降低可能与EM治疗中“孕激素耐受”相关。     

子宫内膜异位症大鼠模型妊娠期孕激素受体及BKCa α表达

目的:探讨子宫内膜异位症(EM)大鼠妊娠模型子宫平滑肌子宫收缩相关因子的表达。方法:皮下种植法建立大鼠EM模型,雌雄合笼观察其受孕情况。留取妊娠期子宫平滑肌组织,qRT-PCR法检测BKCaα(大电导钙依赖的钾通道)、PR(孕激素受体)和PR-B(孕激素受体B亚型)表达情况。结果:造模成功率为16/20(80.00%),EM实验组和对照组的妊娠率分别为12/16(75.00%)和9/10(90.00%),两组比较差异无统计学意义(P=0.63)。内异症孕鼠模型中BKCaα、PR和PR-B mRNA表达分别为3.56±0.62、4.31±2.21和3.41±1.75,对照组分别为3.13±1.47、1.32±0.28和1.54±0.39,两组比较差异均无统计学意义。内异症孕鼠组的PR-B/PR比值显著高于对照组[(32.07±8.13)%vs (14.46±2.87)%,P0.05]。结论:内异症大鼠妊娠期孕激素受体亚型的异常分布可能与子宫异常收缩相关。     

MMP-2、TIMP-2在子宫内膜异位症组织中的表达及其意义

目的研究基质金属蛋白酶-2(MMP-2)及其抑制因子-2(TIMP-2)mRNA在子宫内膜异位症异位和在位内膜组织中的表达及临床意义。方法分别选取子宫内膜异位症异位内膜组织50例、在位内膜组织26例和对照组正常子宫内膜组织22例为研究对象,应用半定量逆转录聚合酶链反应技术(RT-PCR)检测MMP-2、TIMP-2mRNA的表达。结果(1)MMP-2mRNA在异位症异位内膜组织中相对表达量明显高于正常子宫内膜组织和在位内膜,差异均有显著性(P<0.01,P<0.01);TIMP-2mRNA在子宫内膜异位症异位内膜和在位内膜组织中均低表达,其相对表达量分别明显低于正常子宫内膜,差异均有显著性(P<0.01;P<0.01);(2)异位症异位内膜组织中MMP-2mRNA、TIMP-2的表达与r-AFS临床分期无关,差异无显著性(P>0.05)。结论异位和在位内膜组织中MMP-2高表达,TIMP-2低表达,使MMP-2与TIMP-2平衡失调,异位内膜组织侵袭降解ECM的能力增强,从而在子宫内膜异位症中的发生发展中起了重要作用。     

内质网应激介导的细胞凋亡在子宫内膜异位症发病中的作用研究

目的探讨内质网应激介导的细胞凋亡在子宫内膜异位症(endometriosis,EM)发病中的作用。方法选取2009年1月至2010年12月沈阳市第五人民医院妇产科32例EM患者的异位和在位子宫内膜组织,选取同期28例因浆膜下子宫肌瘤手术并经病理证实为正常子宫内膜组织为对照组。采用流式细胞仪检测子宫内膜细胞凋亡率,采用RT-PCR法检测子宫内膜内质网分子伴侣葡萄糖调节蛋白-78(glucose-regulated protein78,GRP-78)、葡萄糖调节蛋白-94(glucose-regulated protein94,GRP-94)和凋亡因子Caspase-12、Caspase-3mRNA的表达,采用Western blot法检测子宫内膜GRP78、GRP94和Caspase-12、Caspase-3蛋白的表达。结果 EM患者异位和在位子宫内膜细胞凋亡率均显著低于正常子宫内膜,且异位子宫内膜细胞凋亡率显著低于在位子宫内膜;EM患者异位和在位子宫内膜GRP78、GRP94和Caspase-12、Caspase-3mRNA及蛋白表达水平均显著低于正常子宫内膜,且异位子宫内膜GRP78、GRP94和Caspase-12、Caspase-3mRNA及蛋白表达水平显著低于在位子宫内膜。结论 EM患者子宫内膜细胞凋亡减少,内质网应激介导的细胞凋亡途径下调可能是EM发病的机制之一。     

孕激素受体、17β羟类固醇脱氢酶与子宫内膜异位症的关系

目的 探讨孕激素受体(PR)、17β羟类固醇脱氢酶(17βHSD)在子宫内膜异位症(内异症)在位与异位内膜的表达与发病的关系.方法 2005年6月至2006年10月在中国医科大学盛京医院和解放军463医院采集内异症(内异症组)38例和宫颈上皮内瘤样病变(对照组)25例行子宫切除的分泌期子宫内膜,内异症患者配对卵巢巧克力囊肿组织作为研究标本.Western印迹杂交检测PRA与PRB蛋白表达,RT-PCR检测17βHSD2mRNA表达.结果 内异症组在位内膜PRA蛋白相对表达量70.79±10.82,对照组78.99±16.02(P＞0.05);内异症组在位内膜PRB蛋白相对表达量64.87±10.10,对照组156.13±21.46,内异症组PRB蛋白表达显著低于对照组(P＜0.01);内异症组卵巢异位内膜PRA蛋白相对表达量67.04±6.90,配对在位内膜70.79±10.82(P＞0.05);卵巢异位内膜PRB蛋白相对表达量60.75±6.73,配对在位内膜64.87±10.10(P＞0.05).内异症组在位内膜17βHSD2mRNA表达量1.04±0.11,对照组1.10±0.16(P＞0.05);卵巢异位内膜17βHSD2mRNA表达量0.17±0.02,配对在位内膜1.04±0.11,异位内膜低于配对在位内膜(P＜0.05).结论 内异症患者在位内膜和异位内膜PRB阴性表达与内异症发病有关;内异症患者异位内膜缺乏17βHSD2与内异症发病有关.     

子宫内膜异位症裸鼠模型子宫内膜的雌、孕激素受体表达

目的:建立子宫内膜异位症裸鼠模型,观察子宫内膜的雌激素受体(ERs)、孕激素受体(PRs)及其亚型的表达情况,为进一步探讨内异症子宫内膜孕激素抵抗的发生机制提供研究模型。方法:建立子宫内膜异位症裸鼠模型,分别于造模后1月、2月、3月取裸鼠子宫内膜,利用RT-qPCR和Western blot法检测其孕激素受体(PRA、PRB)和雌激素受体(ERα、ERβ)表达情况。结果:与对照组相比,内异症组裸鼠内膜的PRB和ERα表达降低,在造模后3月最明显;PR和ERβ表达升高,PRB/PRA和ERα/ERβ比值降低,均在造模后3月最明显。结论:子宫内膜异位症裸鼠模型是研究内异症的理想模型之一,造模后的裸鼠内膜存在孕激素抵抗。     

乙酰肝素酶基因在子宫内膜异位症患者在位与异位子宫内膜组织中的表达

目的　研究乙酰肝素酶基因在子宫内膜异位症发病中的作用。方法　应用原位杂交技术 ,检测腹腔镜手术中证实为子宫内膜异位症患者 (EM组 ,2 3例 )的在位和异位子宫内膜组织乙酰肝素酶mRNA的表达 ,并与正常妇女 (对照组 ,2 5例 )子宫内膜组织比较。结果　 ( 1)EM组在位与异位子宫内膜乙酰肝素酶mRNA阳性表达率一致 ,但异位子宫内膜组织中 ,阳性细胞着色较深。在位子宫内膜腺上皮细胞较间质细胞胞浆染色深 ,异位子宫内膜腺上皮细胞与间质细胞胞浆着色基本一致 ;EM组增生期与分泌期子宫内膜均有乙酰肝素酶mRNA的表达 ,增生期阳性表达率为 83 3%( 10 / 12 ) ;分泌期为 72 7% ( 8/ 11) ,两者比较 ,差异也无显著性 (P >0 0 5 ) ;( 2 )对照组增生期子宫内膜乙酰肝素酶mRNA的阳性表达率为 4 1 7% ( 5 / 12 ) ,分泌期子宫内膜阳性表达率为 7 7% ( 1/ 13) ,两者比较 ,差异有显著性 (P <0 0 5 )。 ( 3)EM组子宫内膜乙酰肝素酶mRNA阳性表达率为 78 3% ( 18/2 3) ;对照组为 2 4 0 % ( 6 / 2 5 ) ,两者比较 ,差异也有显著性 (P <0 0 5 )。结论　乙酰肝素酶基因的表达与子宫内膜异位症的发病相关 ,其可能成为子宫内膜异位症治疗的一个有价值的靶点。     

子宫腺肌病中孕激素受体B表达及甲基化的研究

目的:探讨子宫腺肌病中孕激素受体B(progesterone receptor B,PR-B)表达及其甲基化在疾病发生中的作用。方法:用免疫组化法测定PR-B的表达,甲基化特异性基因扩增(methylation-specific PCR,MSP)方法检测50例子宫腺肌病患者在位与异位内膜和18例输卵管不孕或良性卵巢囊肿患者子宫内膜中PR-B的甲基化状态,并分析甲基化与PR-B表达的相关性。结果:子宫腺肌病患者在位和异位内膜PR-B表达明显低于对照内膜(P0.01);子宫腺肌病异位内膜中PR-B甲基化比率显著高于对照内膜(P0.05);且子宫腺肌病在位和异位内膜中PR-B甲基化状态与PR-B表达相关(P0.05)。结论:PR-B低表达及其甲基化可能与子宫腺肌病的发生有关。     

血管内皮生长因子受体KDRmRNA和flt-1mRNA与子宫内膜异位症相关性研究

目的探讨血管内皮生长因子受体(VEGFR)中的fms样酪氨酸激酶受体(flt-1)和胎肝激酶受体(KDR)在子宫内膜异位症(内异症)患者异位及在位子宫内膜组织中的表达及其意义.方法采用RT-PCR技术,从核酸水平检测53例内异症患者(44例卵巢子宫内膜异位囊肿,30例内异症在位子宫内膜组织)中的VEGF受体KDRmRNA、flt-1mRNA的阳性表达率及相对表达强度,以40例正常子宫内膜组织作为对照.结果与对照组比较,研究组KDRmRNA和flt-1mRNA的阳性表达率高于对照组,差异有显著性(P＜0.05);研究组在位内膜增殖期与分泌期的阳性表达率、相对表达强度高于对照组子宫内膜组织,差异有显著性(P＜0.05);不同月经周期在位内膜组织KDRmRNA和flt-1mRNA的表达、两组增殖期KDRmRNA相对表达强度高于分泌期flt-1mRNA,而flt-1mRNA分泌期相对表达强度高于KDRmRNA.结论VEGF受体KDRmRNA和flt-1mRNA在内异症中有明显表达并呈周期依赖性.VEGF受体在内异症血管生成中的作用,可能与内异症远处转移、侵袭、种植相关.     

白细胞介素-1β及C-反应蛋白与子宫内膜异位症的相关性

目的 探讨参与子宫内膜异位症发生、发展有关的细胞因子白细胞介素-1β(IL-1β)和C-反应蛋白(CRP)在其内膜组织和血清中的表达变化及在子宫内膜异位症发生过程中的作用.方法 选取2005年11月至2006年8月在解放军昆明总医院妇产科就诊的Ⅲ～Ⅳ期卵巢子宫内膜异位症囊肿患者(子宫内膜异位症组)20例及对照组17例(同龄、因其它原因需行子宫内膜诊刮或子宫切除的患者),获取异位和在位子宫内膜组织及患者空腹血,用RT-PCR检测IL-1β mRNA在内膜组织中的表达,用ELISA法检测血清中CRP值.结果 子宫内膜异位症组和对照组子宫内膜IL-1βmRNA表达比较差异具有显著性意义(增生期1.21±0.33和分泌期1.43±0.34对0.54±0.12,P＜0.05);子宫内膜异位症组分泌期内膜组织IL-1β mRNA表达与增生期相比,差异有显著性意义(1.43±0.34对1.21±0.33,P＜0.05);子宫内膜异位症组CRP高于对照组,差异有显著性意义[增生期(5.23±1.72)mg/L和分泌期(6.76±2.23)mg/L对(1.58±0.74)mg/L,P＜0.05].结论 IL-1作为前炎性因子可能参与了内膜组织的局部免疫调控,减低腹膜清除异位内膜细胞的能力,促进子宫内膜细胞的黏附和转移;IL-1β和雌二醇有协同上调作用,促使形成异位内膜的趋化因子增加,参与子宫内膜异位症的发生、发展;CRP的检测对子宫内膜异位症患者的辅助诊断可能有意义.     

Changes in beta-endorphin in fetal membranes and placenta in normal and pathological pregnancies

Several studies indicated that trophoblast tissue synthesizes pro-opiomelanocortin-related peptides. These peptides are also present in amniotic fluid, but their origin remains unknown. The present study evaluated the presence of and the possible changes in beta-endorphin (beta-EP) in amnion and chorion during pregnancy, at parturition and in spontaneous abortion. Amnion, chorion and placental tissues were isolated and homogenized from a total of 46 pregnant women between 4th and 42 th week of pregnancy. Beta-EP was separated on a Sephadex G-75 column and measured by RIA with specific antiserum. The identity of the endogenous opioid with its corresponding reference molecule was confirmed by high performance liquid chromatography. In all tissues, the concentration of beta-EP in the first trimester was significantly higher than in the second trimester. A negative correlation between opioid levels and gestational age was observed in the first two trimesters. At delivery, the beta-EP content of all tissues was greater than in the second trimester. In tissues collected at term, in the absence of labor, beta-EP levels were very low in comparison with those collected after vaginal delivery. Low beta-EP contents were found in membranes collected from spontaneous abortion in 1st trimester. From these data one can surmise the existence of a local endogenous opioid system in fetal adnexes. This system seems sensitive to the stress of vaginal delivery and could be involved in the mechanisms leading to spontaneous abortion.     

Differences in preterm delivery rates and outcomes in Jews and Bedouins in Southern Israel

OBJECTIVE: (1) To compare the preterm delivery rates in the Bedouin versus the Jewish population. (2) To compare risk factors for preterm delivery in the two populations. (3) To compare outcomes of preterm delivery between the two groups. STUDY DESIGN: 41669 Jewish singletons births of whom 2816 delivered preterm (23-36 weeks) and 26495 Bedouin singletons in whom 2064 preterm deliveries occurred, were compared. All births took place in Soroka University Medical Center. Data were obtained from the computerized database of birth discharge records. RESULTS: The incidence of preterm delivery in Bedouin women was significantly higher than the rate in Jewish women (7.8 vs. 6.8%, P<0.01). The grand multiparity rate was higher among Bedouin women (P<0.001), as was the rate of teenage (<19 years) mothers (P<0.001). Gestational diabetes, PIH, and PROM rates were higher in the Jewish population (P<0.001, P=0.017, P<0.001, respectively). A bad obstetric history and previous perinatal mortality is more common in the Bedouin population (P<0.001 for both). In a logistic regression model including all these factors, the ethnic difference in the incidence of preterm delivery remained significant. The neonatal mortality rate was higher in the Bedouin population (P<0.001), as was the rate of congenital malformations (P<0.001). The perinatal mortality of Bedouins was nearly twice that of Jewish neonates with congenital malformations. However, no difference was found when neonates without congenital malformations were compared. Congenital malformations were found to be the strongest predictor of mortality. Ethnicity per se was no longer a predictor of mortality once congenital malformations were included in a logistic regression model, but the interaction of Bedouin ethnicity and congenital malformation was a significant predictor of mortality. CONCLUSION: The incidence of preterm delivery was significantly higher in Bedouin women than in Jewish women. A full explanation for this difference was not found. However, there were significantly higher rates of congenital malformations in the Bedouin preterm delivered infants. There was a much higher rate of neonatal mortality in the Bedouin population and this ethnic difference was fully explained by the presence of congenital anomalies.