妊娠高血压综合征患者蜕膜组织中免疫相关细胞变化的 …

研究妊高征的免疫学发病机制。方法 通过对妊高征患者及正常孕妇胎盘蜕膜组织中免疫相关细胞进行光镜观察，测定淋巴细胞转化率，探讨蜕膜免疫相关细胞的变化与妊高征之间的关系。结果 蜕膜中大颗粒淋巴细胞及凋亡细胞显著增多，ＣＤ５７＾＋细胞数量及ＣＤ４＾＋与ＣＤ８＾＋比例上升，淋巴细胞转化率明显升高。结论 蜕膜中免疫细胞参与了妊高片的免疫学发病机制。     

妊高征患者蜕膜组织中淋巴细胞转化率及细胞因子活性的变化

目的:研究妊娠高血压综合征(简称妊高征)的免疫学发病机制。方法:通过测定妊高征患者及正常孕妇蜕膜组织中淋巴细胞转化率,检测细胞培养液上清中白细胞介素-1(IL-1)、白细胞介素-2(IL-2)及肿瘤坏死因子α的活性,探讨妊高征的免疫学发病机制。结果:实验组淋巴细胞转化率、IL-1、IL-2、TNF-α活性均比对照组高,有显著统计学意义。且IL-2活性升高与淋巴细胞转化率存在明显的直线正相关。结论:蜕膜组织中的细胞因子异常升高及T细胞可能处于高免疫激活状态参与了妊高征的免疫学发病机制。     

妊娠高血压综合征免疫学发病机制的研究

目的：研究妊娠高血压综合征（妊高征）的免疫学发病机制。方法：通过检测妊高征患者及正常孕妇蜕膜组织细胞培养上清液中白细胞介素－１（ＩＬ－１）、白细胞介素－２（ＩＬ－２）和肿瘤坏死因子－α（ＴＮＦ－α）的活性，分析蜕膜免疫细胞因子的变化与妊高征之间的关系。结果：与正常孕妇相比，妊高征患者蜕膜组织中ＩＬ－１、ＩＬ－２和ＴＮＦ－α的分泌显著升高。结论：蜕膜组织免疫微环境中细胞因子的改变可能是妊高征发病的机制之一     

Fas/FasL系统表达异常与妊娠高血压综合征的关系

近年来，免疫因素在妊娠高血压综合征(妊高征)发病机制中的作用越来越受到人们的重视。国外研究发现，Fas/FasL系统在正常母．胎免疫耐受中起重要作用。本研究旨在对妊高征及正常孕妇的血清可溶性Fas(sFas)及胎盘绒毛滋养细胞和蜕膜组织细胞中的Fas／FasL表达进行研究，进一步从分子免疫学角度探讨妊高征发病机制。     

妊高征患者胎盘组织中FasL的表达及其意义

目的　探讨FasL在妊高征患者胎盘组织中的表达是否异常 ,进一步从免疫学角度分析妊高征的发病机制。方法　 2 0 0 1年 11月至 2 0 0 2年 7月 ,采用免疫组织化学SP法检测 2 0例正常孕妇 (对照组 ) ,6 5例妊高征患者 (妊高征组 ,其中轻度 2 2例、中度 2 0例、重度 2 3例 )胎盘组织中FasL表达强度。结果　FasL主要表达于胎盘绒毛滋养细胞 ,妊高征组胎盘绒毛滋养细胞及蜕膜组织细胞FasL表达强度明显低于对照组 (P <0 0 1,P <0 0 5 )。结论　妊高征患者胎盘组织FasL表达减少 ,母胎免疫耐受机制遭到破坏 ,引发胎盘绒毛发育不全、功能下降等一系列免疫病理改变 ,最终可能导致妊高征及其并发症的发生。     

妊高征的免疫学研究

妊高征的免疫学研究关铮，翁霞云有关妊高征的发病原因国内外提出了各种学说，如子宫－胎盘缺血学说，神经内分泌学说，微量元素学说等等，虽然各种学说各有一定的理论基础及实验支持，但均未能全面透彻地解释其发病机制。随着生殖免疫学研究的不断深入，人们对免疫与妊高...     

妊娠高血压综合征合并胎儿生长受限胎盘组织血管细胞粘附分子1的表达

目的：探讨血管细胞粘附分子1（vascular cell adhesion molecule-1,VCAM-1)在妊娠高血压综合征（简称妊高征）合并胎儿生长受限（fetal growth restriction,FGR)发病过程中的作用。方法：采用免疫组化法测定30例妊高征合并FGR患者、28例非妊高征合并FGR及30例正常妊娠者胎盘组织中血管内皮及滋养细胞的VCAM－1表达。结果：妊高征合并FGR组胎盘底蜕膜内血管内皮VCAM－1的表达阳性率（80％）及表达强度（＋＋＋）14例，与正常妊娠组25％（＋＋＋）0例及非妊高征合并FGR组155％（＋＋＋）0例相比明显增高（P＜0．005），而前两者间无显著差异，随妊高征病情加重，其表达强度逐渐增强；胎盘绒毛毛细血管VCAM－1阳性表达强度妊高征合并FGR组（73．3％）和非妊高征FGR组（67．8％）明显增强，与正常组（10％）相比差异有显性（P＜0．005）；所有GFR患者胎盘滋养细胞VCAM－1表达强度明显降低（妊高征FGR为0％，非妊高征FGR组3．6％，正常组40％），并且在妊高征组随妊高征病情加重其表达强度急剧减低。结论：胎盘血管内皮及绒毛滋养细胞异常表达的VCAM－1参与了妊高征引起FGR的病理生理过程，可以作为判定妊高征对胎盘损伤程度的一个指标。     

妊高征患者纤溶酶原激活物抑制剂1型,凝血酶抗凝血酶Ⅲ复合物及D双聚体的变化

目的 测定妊高征患者中的凝固-纤溶因子的变化,探讨胎盘局部凝固-纤溶系统的调节及其在妊高征发病机制中的作用.方法 用放射免疫法测定重度妊高征及正常孕妇的羊水、母体血浆及胎盘组织中纤溶酶原激活物抑制剂1型(PAI-1)、凝血酶抗凝血酶Ⅲ复合物(TAT)及D双聚体(D-dimer)的含量,用人胎盘蜕膜细胞培养系统进行凝血酶负荷试验.结果 在正常妊娠的PAI-1、TAT在羊水中含量分别为(809.2±79.8),(872±214) ng/ml,明显高于母体血浆的(140.9±38.3),(6.1±0.4)ng/ml,胎盘组织中PAI-1含量,蜕膜组织(415.7±39)ng/mg明显高于绒毛组织(93.9±10)ng/mg.在妊高征患者,羊水及胎盘蜕膜组织PAI-1分别为(1 474.5±254.7) ng/ml及(1 164±132) ng/mg蛋白、TAT(132±253.1) ng/ml,D-dimer(132±27.8)ng/ml显著高于正常妊娠.凝血酶可刺激胎盘蜕膜细胞增加PAI-1的产生和分泌,两者存在着量效关系.结论 妊高征中胎盘蜕膜细胞产生和分泌PAI-1水平的增加,使胎盘凝固-纤溶系统发生改变,即凝固亢进,纤溶活性降低.这些改变可能与妊高征发病机制有关.     

内皮素在妊高征发病中的地位

内皮素是迄今所知最强的缩血管物质。妊高征中内皮素继内皮细胞损伤后过量释放，一方面参与妊高征者心血管损伤后修复与重建的保护性机制；另一方面导致全身小血管痉挛，水钠潴留和Ｃａ＾＋＋代谢异常等病理改变，给机体造成不利影响，内皮素是在妊高征发病机制中起主要作用的物质之一，测定血浆内皮素水平有助于妊高征的诊断和鉴别诊断。     

胎盘生长因子与妊娠高血压综合征发病的相关性研究

目的　探讨胎盘生长因子(PLGF)与妊娠高血压综合征（妊高征）发病的关系。方法用酶联免疫吸附法(ELISA)、免疫组织化学染色法和逆转录-聚合酶链反应法(RT-PCR)检测23例妊高征患者(妊高征组)、20例正常妊娠妇女(正常妊娠组)的外周血及其新生儿脐静脉血PLGF水平、胎盘蜕膜PLGF蛋白及其mRNA表达。结果　(1)妊高征组外周血PLGF水平［(112.7±63.8)μg/L］低于正常妊娠组［(200.3±140.9)μg/L］,两组比较,差异有显著性(P<0.05),且与新生儿体重和胎盘重量呈正相关,相关系数分别为0.4、0.6。(2)妊高征组合体滋养细胞、绒毛间质和蜕膜PLGF表达均显著低于正常妊娠组(P<0.01,P<0.01,P<0.05),其合体滋养细胞PLGF表达水平与妊高征病情的轻、重有关。(3)妊高征组胎盘和蜕膜组织总PLGFmRNA表达均显著低于正常妊娠组(P<0.05,P<0.05),尤其胎盘组织主要表现为PLGF-2mRNA表达明显下降(P<0.01)。结论　PLGF的表达异常在妊高征发病中起着重要作用。     

Expression of intercellular adhesion molecule-1 on the surface of peripheral blood and decidual lymphocytes of women with pregnancy-induced hypertension

OBJECTIVE: If overexpression of intercellular adhesion molecule-1 (CD54) on lymphocytes exists it could have important implications for the pathophysiology of pregnancy-induced hypertension (PIH). STUDY DESIGN: CD54 "in vitro" expression (described as (%) of CD54+cells and CD54 mean fluorescence intensity, MFI) on the peripheral blood and decidual lymphocytes of pregnant with pre-eclampsia (PE) (n=16), transient hypertension (TH) (n=12), and controls (n=9). RESULTS: The percent (%) of CD54+peripheral blood lymphocytes, CD54 MFI on them and CD54 MFI on decidual lymphocytes were increased especially in PE. During PE the (%) of CD54 decidual lymphocytes correlated negatively with platelet count. In TH the positive correlation between the blood pressure and the (%) of CD54 peripheral blood lymphocytes as well as CD54 MFI on decidual lymphocytes were found. CONCLUSIONS: (1) PIH, especially PE, is accompanied by overexpression of intercellular adhesion molecule-1 (ICAM-1) on peripheral blood and decidual lymphocytes studied "in vitro", (2) Some of the parameters studied seem to correlate with clinical markers of PIH intensity but this fact needs further investigations using larger subject groups.     

Decidual lymphocyte subsets in pregnant women

OBJECTIVES: Materno-foetal immunological reactions in decidua are probably one of the most important elements in pathogenesis of preeclampsia. DESIGN: To compare lymphocyte subsets isolated from decidua of preeclamptic pregnant women with lymphocyte subsets isolated from healthy pregnant women. MATERIALS AND METHODS: Preeclampsia (PE) was defined according to USA National Health Institute criteria. The study group consisted of 21 women with PE and 11 women with physiological pregnancy. All pregnancies were finished with elective cesarean sections. Exclusion criteria were: uterine contractions, infection, chorinamnionitis, diabetes mellitus and therapy with steroids less than 7 days before blood sampling. Decidual tissue was obtained by curettage of the uterine cavity. The fragments of decidua were separated from clotted blood and placed in sterile tubes with 5 ml of isotonic solution (PBS). Then the decidual tissue was mechanically fragmented, homogenized and rinsed in PBS. Routine immunofluorescent marking techniques with monoclonal antibodies were performed. Analysis was done with FACSCalibur flow-cytometer with 488 nm argon laser using CellQuest programme. The following lymphocyte subsets were estimated: CD3, CD19, CD4, CD8, CD4/CD29, CD8/CD28, CD4/CD45RA, CD4/CD45RO, CD56/CD16, CD69. The results were described as percentage of lymphocytes positive for above surface molecules. Statistical analysis was performed using t-Student and U-Mann-Whitney tests. The work was sponsored by KBN 4 P05E 118 15 grant. RESULTS: Decidua of pregnant PE women contains significantly increased percentage of CD3-/ CD56 + 16+, CD8+/CD28+ cells and decreased percentage of CD3+, CD19+, CD4+/CD29+ and CD4+/CD45RA+ compared to decidua of healthy pregnant controls. CONCLUSIONS: These changes suggest that deficiency of suppressor activity as well as aberrant immunoregulation exists in decidual tissue of PE women.     

不明原因习惯性流产患者蜕膜自然杀伤细胞活性及表型的研究

目的 :探讨原因不明习惯性流产 (UHA)患者蜕膜自然杀伤 (NK)细胞的数量、表型特征及杀伤活性 ,探讨其在UHA发病中的作用。方法 :选取确定妊娠并难免流产的UHA 32例 ,选取 2 0例正常妊娠行人工流产者作为对照组 ,用流式细胞仪检测两组蜕膜组织中NK细胞数量及表型 ,用改进的乳酸脱氢酶释放法测定NK细胞杀伤活性。结果 :正常早孕蜕膜中CD5 6+CD3- NK细胞占蜕膜单个核细胞的 60 .73± 13.2 4 % ,为蜕膜组织的优势细胞群 ,UHA患者蜕膜中CD5 6+CD3- NK细胞总量与正常妊娠蜕膜组织中相同 ,而其CD5 6+CD16- 亚群却明显低于正常妊娠组 (P <0 .0 5 ) ,CD5 6+CD16+亚群含量及CD5 6+CD16+/CD5 6+CD16- 比值均异常增高 (P均 <0 .0 5 )。UHA组蜕膜组织中NK细胞杀伤活性及其异常增高率均高于正常妊娠组 ,差异均有显著性 (P均 <0 .0 5 )。结论 :NK细胞是孕早期蜕膜组织中的优势细胞群 ,其亚群失衡及功能异常可导致自然流产     

Study on the activity and phenotype of decidual natural killer cells in patients with unexplained habitual abortions

Habitualabortionsoccurin 1to 2 %ofthechild bearingpopulation .Chromosomalaberrationistheprincipalcauseoffetallossduringtheearlystageofgestation .Oth eretiologies ,whichincludeanatomicanomalies ,endocrinedisorders,andinfections ,havealsobeendocumemtedinpatientswithhabitualabortions .Nevertheless ,in 4 0to6 0 %ofcouples ,habitualabortionsremainunexplained ,whicharecalledUHA .Recently ,theimportanceofim munologyinUHAisrecognized .Immunecellsareabun dantinhumandeciduaandarecapableofrespondingto…     

早孕妇女血清及蜕膜组织液对自然杀伤细胞活性及淋巴细胞增殖的影响

目的　探讨早孕妇女血清及蜕膜组织液对自然杀伤 (NK)细胞及淋巴细胞功能的影响。方法　采用同位素掺入法 ,检测 3 2例正常早孕妇女血清 (早孕血清组 )及蜕膜组织液 (蜕膜组织液组 )对正常妇女外周血中NK细胞活性 (% )及淋巴细胞增殖功能的影响 ,并采用 2 5例正常未孕妇女的血清作对照 (对照组 )。结果　早孕血清组、蜕膜组织液组及对照组的NK细胞活性分别为 (3 5 .8±3 .0 ) %、(19.1± 2 .9) %及 (46.1± 3 .2 ) % ,淋巴细胞增殖功能 [每分钟同位素放射次数 (CPM) ]分别为(3 689± 4 5 6)CPM、(2 0 5 9± 2 88)CPM及 (4883± 64 3 )CPM ,3者间差异均有极显著性 (P <0 .0 1) ,且蜕膜组织液组均显著低于早孕血清组 (P <0 .0 0 5 )。结论　正常早孕妇女血清及蜕膜组织液具有免疫抑制作用 ,而蜕膜组织液可能是调节早期妊娠子宫局部免疫功能的重要因素之一。     

Immunological modulation of lymphocyte subpopulation in cervical cancer tissue by sizofiran and OK-432.

The intimate correlation between marked lymphocyte infiltration in the cancer tissue and the superior clinical prognosis has been reported in human cancers. Sizofiran (SPG), a polysaccharide consisting of beta-1,3-D-glucopyranosyl linkage with beta-1,6-D-glucopyranosyl branches, or OK-432, a heat- and penicillin-treated, lyophilized preparation of the Su strain of Streptococcus pyogenes of human origin, was administered intratumorally to nine patients with advanced uterine cervical carcinoma before radical hysterectomy to assess their immunological modulating properties to tumor-infiltrating lymphocyte subpopulations immunohistochemically. The degree of infiltration of CD3- and CD5-positive cells increased moderately or markedly in the stroma surrounding the lesion in both SPG group and OK-432 group, as well as that of CD4- and CD8-positive cells, from that before administration. The density of infiltration of CD3-positive, CD4-positive, and CD8-positive cells in the lesion increased slightly or moderately in both groups after administration. As for CD16-positive cell infiltration, both SPG and OK-432 increased its degree in the stroma lining the lesion while SPG alone augmented its degree in the lesion. This augmentation of lymphocyte infiltration in situ induced by intratumoral administration of SPG and OK-432 is expected to lead to a favorable prognosis of patients with cervical cancer.     

Tumor-associated glycoprotein (TAG-72) is a natural ligand for the C-type lectin-like domain that induces anti-inflammatory orientation of early pregnancy decidual CD1a+ dendritic cells

Tumor-associated glycoprotein-72 (TAG-72) is physiologically present in secretory phase endometrium, but its presence and possible immunological role in early normal human pregnancy decidua has not received attention. The double labeling of paraffin-embedded early pregnancy decidua sections using B-72.4 anti-TAG-72 mAb and MNF 116 anti-cytokeratin mAb revealed the absence of TAG-72 in uterine decidua of normal and pathological pregnancies (non-embryonic pregnancy and missed abortion) at the implantation sites, although it was present in epithelial cells at and away from the tubal implantation site of an ectopic pregnancy. TAG-72 binds and internalizes by reacting with the mannose receptor (MR-CD206) or with DC-specific ICAM reacting non-integrin (DC-SIGN-CD209) on decidual CD1a+ cells. Decidual CD1a+ cells stimulated with TAG-72 decreased CD83 expression and diminished IL-15 and IFN-γ intracellular production. TAG-72-treated CD1a+ cells decreased IFN-γ production in syngenic decidual and allogenic cord blood T cells even in the presence of lipopolysaccharide. TAG-72- and lipopolysaccharide-pre-treated CD1a+ cells significantly increased IL-4 expression in allogenic cord blood T cells. TAG-72 increased allogenic cord blood T cell proliferation, mediated by decidual CD1a+ cells, compared with its effect on the proliferation of syngenic decidual T cells. All these data emphasize the anti-inflammatory properties of TAG-72-treated decidual CD1a+ cells in terms of their interaction with T cells. Thus, the absence of TAG-72 at the maternal-fetal interface during early pregnancy could lead to a mild pro-inflammatory response that may be beneficial for pregnancy success and trophoblast growth control.     

卵巢癌患者自体细胞因子诱导杀伤细胞治疗前后免疫功能的检测与分析

目的观察卵巢癌患者自体细胞因子诱导杀伤细胞治疗前后患者外周血淋巴细胞亚群的变化,为综合评价临床应用CIK细胞疗法治疗卵巢癌的效果提供依据。方法2004-2005采集中国医科大学附属第一医院5例卵巢癌患者的外周血单个核细胞,经多种细胞因子诱导制成CIK细胞,回输前及回输后取患者外周血,流式细胞仪测定外周血淋巴细胞亚群的变化。结果诱导培养后,CD3+/CD56+效应细胞的比例明显升高;CIK细胞回输后患者外周血CD3+、CD3+/CD8+、CD3+/CD56+阳性淋巴细胞亚群的比例明显升高。结论CIK细胞疗法可以提高卵巢癌患者的细胞免疫功能,提高对肿瘤细胞的杀伤作用。