子宫内膜异位症患者NK细胞功能状态的研究

目的：探讨子宫内膜异位症(EMs)患者外周血和异位内膜中NK细胞的组成比例及其功能表型的变化情况。方法：收集25例子宫内膜异位症患者外周血和异位内膜组织,同时取25例子宫肌瘤患者的外周血和子宫内膜组织作为对照,用流式细胞检测术(FACS)检测CD56~ CD3~-、CD56~ CD16~ 、CD56~ CD16~-NK细胞的数量变化,检测NK细胞表面激活性受体(CD56~ NKG2D~ )和抑制性受体(CD56~ NKG2A~ )的表达情况。结果：子宫内膜异位症患者外周血中NK细胞的含量与对照组比较无显著变化(P＞0．05),异位内膜组织中CD56~ CD3~-和CD56~ CD16~- NK细胞减少和CD56~ NKG2D~ 减少(P＜0．05)。结论：子宫内膜异位症患者异位病灶局部的NK细胞功能状态发生改变,局部的免疫抑制状态可能导致异位病灶的发生和发展。     

子宫内膜异位症患者雌激素受体基因的多态性研究

遗传流行病学研究提示 ,子宫内膜异位症 (内异症 )是一种多基因遗传性疾病[1,2 ] 。雌激素与内异症发病、发展有密切的关系 ,我们选择雌激素受体 (ＥＲ)基因为候选基因 ,探讨ＥＲ基因ＰｖｕⅡ、ＸｂａⅠ的多态性与内异症的关系。一、材料和方法1 研究对象 :观察组为 2 0 0 0年 2月～ 2 0 0 1年 8月 ,在复旦大学附属妇产科医院住院治疗 ,经腹腔镜活组织检查 ,并经病理学证实为内异症的患者 ,共 63例 ,年龄为 2 1～ 5 0岁 ,平均为 (3 5± 9)岁。对照组为同期住院患者 ,经腹腔镜或开腹手术证实无内异症 ,且无子宫肌瘤、子宫腺肌病的患者 ,共41…     

Toll样受体与子宫内膜及子宫内膜异位症

子宫内膜异位症(EMs)发病机制尚未完全阐明.大量研究表明,免疫因素在EMs的发病机制中起重要作用.EMs免疫应答异常主要是巨噬细胞数量和活性增加及其分泌产物,如生长因子、细胞因子和血管生成因子的改变.Toll样受体(TLRs)识别特异性的病原体相关分子模式,启动和介导免疫应答,在固有免疫中发挥重要作用,并诱导产生适应性免疫反应.TLRs在正常子宫内膜中的生理作用以及在EMs中的相关研究已逐步开展,对其深人认识和研究将为EMs诊断、治疗和预后判断提供新思路和手段.     

子宫内膜异位症患者内膜细胞中孕激素受体与凋亡因子Bcl-2、Bax表达的研究

目的:通过检测孕激素受体(PR)、凋亡抑制基因Bcl-2、促凋亡基因Bax(bcl-associated x protein)在子宫内膜异位症(EMT)中的表达,研究PR与Bcl-2、Bax的关系,探讨EMT的发病机制及选择更有效的药物治疗方案.方法:用免疫组织化学方法及图像分析技术检测PR、Bcl-2、Bax在EMT患者异位及在位内膜细胞中的表达情况.结果:两种检测方法检测结果一致,异位内膜PR、Bcl-2表达低于在位内膜(P<0.05),异位内膜Bax表达高于在位内膜(P<0.05),在位内膜与异位内膜PR、Bcl-2、Bax增殖期与分泌期表达差异无统计学意义(P>0.05).结论:无论是增殖期还是分泌期,EMT中在位内膜PR表达均高于异位内膜及正常内膜,使在位子宫内膜细胞持续低水平增殖,更易于迁徙和种植.在位内膜及异位内膜中Bcl-2和Bax的表达均与子宫内膜周期性改变无关,不受卵巢激素调节,EMT细胞凋亡持续性减弱,增殖性能持续性增强.     

Toll样受体与子宫内膜及子宫内膜异位症

子宫内膜异位症（EMs）发病机制尚未完全阐明。大量研究表明,免疫因素在EMs的发病机制中起重要作用。EMs免疫应答异常主要是巨噬细胞数量和活性增加及其分泌产物,如生长因子、细胞因子和血管生成因子的改变。Toll样受体（TLRs）识别特异性的病原体相关分子模式,启动和介导免疫应答,在固有免疫中发挥重要作用,并诱导产生适应性免疫反应。TLRs在正常子宫内膜中的生理作用以及在EMs中的相关研究已逐步开展,对其深入认识和研究将为EMs诊断、治疗和预后判断提供新思路和手段。     

子宫内膜异位症患者雌,孕激素受体及生长因子的研究

子宫内膜异位症患者雌、孕激素受体及生长因子的研究卢美松沈铿郎景和子宫内膜异位症（内异症）的发病率逐年增高，已成为生育期妇女的常见病和多发病。由于患者年龄较轻，而且影响生育、容易复发，临床处理十分棘手。为了探讨内异症的发生、复发机理及相关因素，不少学者...     

孕激素受体与子宫内膜异位症的研究进展

子宫内膜异位症是妇女盆腔痛常见原因。孕激素可抑制异位内膜生长和炎症反应，但部分患者对孕激素治疗不敏感．这种孕酮抵抗的分子学基础可能与孕激素同源受体B（PRB）有关。孕激素作用于正常子宫内膜间质细胞诱导产生旁分泌因子，后者作用于相邻的上皮细胞，诱导产生17β羟类固醇脱氢酶（17βHSD2），该酶则将雌二醇（E2）灭活为雌酮。异位内膜间质细胞缺陷，缺乏PRB孕激素不能诱导产生旁分泌因子进而产生17βHSD2，最终使异位内膜E2增加。介绍子宫内膜异位症孕酮抵抗和异位内膜E2代谢异常分子生物学机制。     

子宫内膜异位症患者外周血及腹腔液中自然杀伤细胞活性的测定

目的：探讨自然杀伤（ＮＫ）细胞活怀在子宫内膜异位症（内异症）发病中的作用。 杉４－甲基偶氮唑盐（ＭＴＴ）法检测７２例内异症患者（内异症组）外周血及腹腔液中ＮＫ细胞活性。并在内异症不孕妇女（不孕组）和正常妇女（对照组）进行比较。结果：内异症组外周血及腹腔液与低于对照组（Ｐ〈０．００１）和不孕组（Ｐ〈０．００１），且均随期别的增加而递减，与临床分期呈显著负相关（Ｐ〈０．０１）。对８例Ⅲ、Ⅳ人异症患者随     

子宫内膜异位症患者子宫内膜IL-18表达的研究

目的 :研究子宫内膜异位症患者子宫在位内膜和异位内膜IL 18的表达 ,探讨IL 18在内异症发病机制中的意义。方法 :用免疫组化和半定量逆转录聚合酶链反应法检测对照组子宫内膜、子宫腺肌症患者子宫内膜和内异症患者的子宫在位内膜与异位内膜IL 18蛋白的表达位置及其mRNA表达水平。结果 :各组标本IL 18蛋白和mRNA的表达均阳性 ,内异症患者子宫在位内膜与异位内膜的IL 18mRNA表达水平分别为 1.0 5±0 .4 0、0 .77± 0 .39,均低于对照组子宫内膜 (1.6 5± 0 .6 4) ,差异有显著性 (P <0 .0 5 ) ;子宫腺肌症组IL 18mRNA表达水平为 1.6 3± 0 .6 0 ,与对照组子宫内膜IL 18mRNA表达水平差异无显著性。结论 :IL 18可能参与了子宫内膜异位症的发病 ,IL 18mRNA在内异症患者在位和异位内膜的低水平表达 ,可能是影响内异症形成和发展的重要因素之一。     

盆腔外子宫内膜异位症的诊治进展

子宫内膜异位症（endometriosis，EMs）是育龄期妇女常见的良性疾病之一，发病率正逐年上升。EMs是指子宫内膜组织出现在正常子宫内膜以外的部位，大多累及盆腔脏器和壁腹膜，如卵巢、骶韧带等。EMs的发病机制尚未完全明确，目前普遍接受的理论有经血逆流假说、体腔上皮化生假说、医源性种植、淋巴转移和血行播散假说等。诊断可依靠临床表现、影像学检查和病理学结果。治疗方式主要有药物治疗和手术治疗。盆腔外子宫内膜异位症（extra-pelvic endometriosis）是一种少见的EMs，发生在盆腔以外的部位，如腹壁、胸腔及会阴等。由于其发病较少，临床症状不典型，因此往往诊断较为困难，常会误诊。为提高盆腔外EMs的诊疗水平，要力求做到早期发现、及时诊断和规范化治疗，以改善患者预后。     

Increased killer inhibitory receptor KIR2DL1 expression among natural killer cells in women with pelvic endometriosis

OBJECTIVE: To investigate the host immunologic response to endometriosis in terms of killer inhibitory receptor (KIR) expression by natural killer (NK) cells. DESIGN: Case-control study of immunologic markers. SETTING: University hospital. PATIENT(S): We compared cells from Japanese women with laparoscopically diagnosed endometriosis to cells from 40 women with other laparoscopic diagnoses. INTERVENTION(S): Peripheral venous blood sampling and laparoscopic peritoneal fluid collection. MAIN OUTCOME MEASURE(S): Flow cytometry was used to assess expression of KIR by NK cells in the cell samples. RESULT(S): The percentage of cells that expressed KIR2DL1 among NK (KIR2DL1(+)NK) cells in peritoneal fluid and peripheral blood was significantly higher in women with endometriosis than in controls. The proportion of KIR2DL1(+)NK cells in peripheral blood NK cells before and 1 month after laparoscopic surgery did not differ significantly. CONCLUSION(S): The proportion of KIR2DL1(+)NK cells was increased in peritoneal fluid and peripheral blood in women with endometriosis; this difference is probably related to NK cell suppression in endometriosis. This increase in KIR2DL1 expression by NK cells may represent a risk factor in the pathogenesis of endometriosis.     

In vitro effect of gonadotropin-releasing hormone agonist on natural killer cell cytolysis in women with and without endometriosis

OBJECTIVE: The purpose of this study was to assess the in vitro effect of gonadotropin-releasing hormone agonist on natural killer cell activity in women with and without endometriosis and to ascertain whether gonadotropin-releasing hormone agonist effects on natural killer cell activity are direct or mediated solely through the hypoestrogenic state that they produce in vivo. STUDY DESIGN: With use of a chromium 51 release microcytotoxicity assay with K562 target cells, natural killer cell activity was measured after the incubation of mononuclear cells with leuprolide acetate that was obtained from 16 patients with endometriosis and 11 control subjects. RESULTS: The cytotoxicity of natural killer cells that were obtained from patients with endometriosis was reduced significantly (P<.001) with leuprolide. Natural killer cell cytotoxicity from control patients was also significantly decreased (P=.005) with gonadotropin-releasing hormone agonist. Natural killer cell cytotoxicity was significantly lower in patients with endometriosis than in control patients (P=.029). CONCLUSION: These findings suggest a direct immunomodulatory role of gonadotropin-releasing hormone agonist on natural killer cell activity and confirm previous findings that patients with endometriosis have reduced natural killer cell cytotoxicity.     

复发性自然流产患者外周血淋巴细胞Fas表达及其与NK细胞毒性的相关性研究

目的:探讨复发性自然流产(RSA)患者的外周血淋巴细胞Fas表达并分析NK细胞毒性与其Fas表达的相关性。方法:应用流式细胞仪技术检测25例RSA患者外周血淋巴细胞Fas表达及NK细胞毒性,对NK细胞Fas表达与其毒性进行相关性分析。结果:正常组表达Fas的CD4+T淋巴细胞为21.06%±4.36%,RSA组为18.27%±4.81%,两组比较无统计学差异(P>0.05)。RSA组表达Fas的CD8+T淋巴细胞为12.32%±2.78%,较正常组(7.78%±2.17%)高,差异有统计学意义(P<0.01)。RSA组表达Fas的NK细胞为14.23%±3.67%,较正常组(8.87%±2.95%)高,差异有统计学意义(P<0.01)。表达Fas的NK细胞含量与NK细胞毒性呈显著正相关。效应细胞:靶细胞为25:1时,相关系数r=0.693,(P<0.01)。效应细胞:靶细胞为50:1时,r=0.672(P<0.01)。结论:RSA患者存在CD8+T淋巴细胞和NK细胞的异常激活,外周血NK细胞毒性增高与表达Fas的NK细胞增多有关。     

子宫内膜异位症患者细胞免疫功能的测定

通过测定子宫内膜异位症患者细胞免疫功能以探讨其发病因素。采用单克隆抗体（ＣＤ３、ＣＤ４、ＣＤ８、ＣＤ５６）对２０例子宫内膜异位症患者，２０例子宫肌瘤患者，２０例正常妇女外周血Ｔ淋巴细胞亚群进行检测。结果：与正常妇女比较，内异症组Ｔ３、Ｔ４、Ｔ４／Ｔ８明显下降，有显著差异（ｐ〈０．０１）；Ｔ８稍高（ｐ〉０．０５）。与肌瘤组比较，内异症组Ｔ４、Ｔ８稍低，Ｔ３相近，Ｔ４／Ｔ８稍高，无显著差异（ｐ〈０．０     

Killer immunoglobulin-like receptor repertoire on uterine natural killer cell subsets in women with recurrent spontaneous abortions

Objective

The objective of this study is to investigate the distribution of inhibitory and activating killer immunoglobulin-like receptors (KIRs) on uterine natural killer (uNK) cells and the compatibility of KIR/HLA-C at the maternal–fetal interface in women with unexplained recurrent spontaneous abortion (RSA) in the Chinese population.

Study design

Sixteen patients with unexplained recurrent spontaneous abortion were enrolled in this study. The PCR sequence-specific primers (SSP) method was used to detect the inhibitory/activating KIRs in uterine NK cells and the HLA-C gene polymorphism expressed on the trophoblast.

Results

The frequencies of inhibitory KIR2DL2 in the RSA group were increased significantly compared with those of the controls. The other inhibitory KIR2DL families did not show significantly different frequencies in the RSA group. No difference in numbers of inhibitory KIR genes with statistical significance was observed between the RSA group and the controls. When analyzing activating KIRs, none of the KIR2DS1–5 family showed statistically different frequencies in the RSA group compared with the controls. Similarly, there was no statistically significant difference between the numbers of activating KIR genes in the RSA group and the controls. Finally, the matching of the inhibitory or activating KIRs/HLA combination at the maternal–fetal interface did not play a dominant role in the pathogenesis of pregnancy loss.

Conclusions

This study suggests that the imbalance of inhibitory and activating KIRs in uterine NKs might confer susceptibility to the occurrence of pregnancy loss. The maternal inhibitory/activating KIRs-HLA-C polymorphism expressed on trophoblast cells from decidual tissues seems to play a limited role in abortion.     

Uterine natural killer cells dysregulation in idiopathic human preterm birth: a pilot study

Objective: To compare between uterine natural killer (uNK) cells in the placental samples of preterm birth and term labor.

Study design: Two-arm case–control study. This study included 60 participants divided into two groups. The first group included 30 cases of idiopathic spontaneous preterm labor and the other group included 30 women who delivered by a spontaneous term vaginal delivery and with no history of previous preterm labor.

Result(s): There were no CD16^? CD56^bright uNK cells in either groups; CD16⁺ CD56^dim uNK cells were present in only 1 case out of 30 term delivery placentae (3.3%), whereas they were found in 21 cases out of 30 (70%) preterm placental samples with a significant statistical difference (p?+CD56^dim uNK cells were found to be invading both the villi and the decidua in 11 cases (70%), whereas those cells were found invading only the villi in 10 cases (33.3%).

Conclusion: CD16⁺CD56^dim cells are expressed in both the decidua and the villi of patients with idiopathic preterm labor suggesting an association between uNK cells dysregulation and idiopathic human preterm labor.     

Expression patterns of lectin-like natural killer receptors, inhibitory CD94/NKG2A, and activating CD94/NKG2C on decidual CD56bright natural killer cells differ from those on peripheral CD56dim natural killer cells

The balance of inhibitory and activating natural killer (NK) receptors on maternal decidual NK cells, most of which are CD56^bright, is thought to be crucial for the proper growth of trophoblasts in placenta. A lectin-like NK receptor, CD94/NKG2, is the receptor for human leukocyte antigen (HLA)-E, which is expressed on trophoblasts. To clarify the mechanism regulating the activity of decidual NK cells during pregnancy, we investigated the expression patterns of inhibitory NK receptor, CD94/NKG2A, and activating receptor, CD94/NKG2C, on decidual NK cells in an early stage of normal pregnancy and compared them with those on peripheral NK cells, most of which are CD56^dim. The rate of NKG2A-positive cells was significantly higher for decidual CD56^bright NK cells than for peripheral CD56^dim NK cells, but the rates of NKG2C-positive cells were comparable between the two cell types. Interestingly, peripheral CD56^dim NK cells reciprocally expressed inhibitory NKG2A and activating NKG2C, but decidual CD56^bright NK cells that expressed activating NKG2C simultaneously expressed inhibitory NKG2A. The co-expression of inhibitory and activating NKG2 receptors may fine-tune the immunoregulatory functions of the decidual NK cells to control the trophoblast invasion in constructing placenta.     

Expression of oct-4 and c-kit antigens in endometriosis

The objective of this study was to test the expression of the oct-4 and c-kit, both markers of stem cells, in the ectopic endometrial tissue of endometriotic lesions of women with severe endometriosis. Our findings show that ectopic epithelial cells express oct-4 and c-kit and this suggests that the ectopic endometrium in endometriosis has a stem cell origin and could explain the possible progression to ovarian cancer.