人类白细胞抗原G与子痫前期的相关性

人类白细胞抗原G（HLA—G）为非经典的HLA—I类分子,特异性高表达于母胎界面的绒毛外滋养细胞．通过诱导免疫耐受对妊娠和胚胎起到保护作用。子痫前期是产科领域危害母婴健康的主要疾病之一．子痫前期患者血清及胎盘组织HLA—G表达下降,但具体作用机制仍不清楚。随着基础研究的深入,明确了HLA—G基因、蛋白质的结构及遗传方式,在基因多态性方面做了大量研究工作,力求从基因水平阐明其与子痫前期的关系。发现部分子痫前期患者可能存在HLA—G基因缺陷,且HLA—G多态性在子痫前期及正常妊娠者中分布也不同。     

子痫前期可溶性人类白细胞抗原G测定及意义

目的 探讨可溶性人类白细胞抗原G(sHLA-G)在子痫前期发病中的意义.方法 应用酶联免疫吸附试验(EUSA)法测定2007年2月至2008年2月第四军医大学唐都医院33例重度子痫前期患者及33例正常足月妊娠妇女外周静脉以及胎盘附着处子宫静脉血中可溶性HLA-G水平.结果 重度子痫前期组外周静脉血中可溶性HLA-G表达水平为(24.04±16.01)kU/L,明显低于正常妊娠组的(38.38±22.15)kU/L,两组比较差异有统计学意义(P<0.05).重度子痫前期组子宫静脉血中可溶性HLA-G表达水平为(26.93±17.22)kU/L,明显低于正常妊娠组的(40.92±18.27)kU/L,两组比较差异有统计学意义(P<0.05).重度子痫前期组外周血可溶性HLA-G表达水平低于子宫静脉血,差异有统计学意义(P<0.05).结论 HLA-G水平的降低与子痫前期发病有关.胎盘可能为HLA-G来源之一.     

重度子痫前期患者可溶性人类白细胞抗原G在血浆和胎盘组织中的表达

目的:研究可溶性人类白细胞抗原G(sHLA-G)在孕晚期重度子痫前期患者血浆的含量水平及其亚型mRNA在胎盘组织中的表达,探讨sHLA-G的来源及其在子痫前期发病中的意义.方法:选择2008年10月至2009年4月第四军医大学唐都医院重度子痫前期患者20例(重度子痫前期组),20例正常足月妊娠者(正常足月妊娠组)及20例正常未妊娠者(正常未妊娠组).采用酶联免疫吸附法(ELISA)检测血浆sHLA-G的含量;采用实时荧光定量PCR法比较sHLA-G亚型(HLA-G5、G6)mRNA在重度子痫前期组和正常足月妊娠组胎盘组织表达的差异.结果:①重度子痫前期组血浆sHLA-G含量水平明显低于正常足月妊娠组(P<0.05),正常未妊娠组与重度子痫前期组和正常足月妊娠组比较,差异有统计学意义(P<0.05).②重度子痫前期组胎盘HLA-G5、G6 mRNA相对表达量(0.32)明显低于正常足月妊娠组相对表达量(1.0).结论:重度子痫前期患者血浆sHLA-G及其胎盘组织中亚型mRNA含量水平均降低,可能与子痫前期发病有关,胎盘可能是sHLA-G的来源之一.     

人白细胞抗原G与先兆子痫

特异的仅表达于绒毛外滋养细胞表面的人白细胞抗原G(HLA-G)可通过多种途径在局部发挥免疫抑制作用,是母胎免疫耐受的主要机制之一.先兆子痫患者胎盘滋养细胞HLA-G存在表达缺陷,可能因此引发滋养细胞易受母体免疫攻击,并与先兆子痫滋养细胞功能异常及其发病有关.     

人类白细胞抗原G与妊娠期高血压疾病

人类白细胞抗原G(HLA-G)是一种非经典HLA-1分子,特异性高表达于绒毛外滋养细胞,其初级转录产物经过不同的剪接可形成至少7种亚型.组织特异性和低多态性的HLA-G,协同妊娠子宫最主要的免疫细胞子宫自然杀伤(uNK)细胞,诱导母胎界面的免疫耐受,促进滋养细胞和胎盘的生长发育.HLA-G在滋养细胞的正常表达,是维持妊娠的必要条件,其表达异常可能导致病理妊娠如妊娠期高血压疾病等.     

人类白细胞抗原G与妊娠期高血压疾病

人类白细胞抗原G(HLA-G)是一种非经典HLA-Ⅰ分子,特异性高表达于绒毛外滋养细胞,其初级转录产物经过不同的剪接可形成至少7种亚型。组织特异性和低多态性的HLA-G,协同妊娠子宫最主要的免疫细胞子宫自然杀伤(uNK)细胞,诱导母胎界面的免疫耐受,促进滋养细胞和胎盘的生长发育。HLA-G在滋养细胞的正常表达,是维持妊娠的必要条件,其表达异常可能导致病理妊娠如妊娠期高血压疾病等。     

青海地区子痫前期患者HLA-GmRNA及蛋白表达研究

目的:探讨青海高原地区子痫前期患者人类白细胞相关抗原G(HLA-G)mRNA、蛋白表达情况及临床意义。方法:收集2011年9月至2011年12月在青海大学附属医院产科分娩的30例子痫前期患者和30例正常妊娠妇女的胎盘组织和血清样品,采用实时荧光定量PCR及West-ernblot分析检测HLA-GmRNA和蛋白在正常妊娠与子痫前期患者胎盘中的表达差异,并应用双抗体夹心酶联免疫吸附法(ELISA)检测血清中可溶性HLA-G的表达。结果:①青海高原地区子痫前期患者胎盘组织中HLA-GmRNA、蛋白表达水平明显低于正常妊娠组,差异有统计学意义(P<0.05)。②子痫前期患者血清中可溶型HLA-G(sHLA-G)浓度明显低于正常妊娠组,差异有统计学意义(P<0.05)。结论:HLA-G基因转录的下调及其蛋白质表达下降,在青海高原地区子痫前期的发生发展过程中可能发挥重要作用。     

载脂蛋白E基因多态性与子痫前期的相关性

目的 探讨载脂蛋白E(apolipoprotein E,ApoE)基因多态性与子痫前期发生的关系.方法 应用聚合酶链反应-限制性片段长度多态性分析(PCR-RFLP)技术对2007年1月至12月广东省妇幼保健院96例子痫前期患者和98例正常孕妇进行不同ApoE基因型分析,并观察两组血脂情况.结果 (1)子痫前期患者血清总胆固醇(TC)、甘油三脂(TG)、低密度脂蛋白胆固醇(LDL-C)显著升高,高密度脂蛋白胆固醇(HDL-C)显著下降(P<0.05).(2)在研究总人群中,ApoE等位基因频率分布分别为ε2(5.7%),ε3(85.8%),ε4(8.5%).在不同的ApoE基因型组,血脂水平不同,并且差异有统计学意义(P<0.01).TC、TG和LDL-C水平均按E3/4+E4/4组>E3/3组>E2/2+E2/3组的顺序降低,HDL-C水平按上述顺序升高.(3)子痫前期组ε3等位基因频率79.7%,明显低于对照组91.8%(P<0.05),ε4等位基因频率13.O%,明显高于对照组的4.1%,差异有统计学意义(P<0.01).结论 ApoE ε4等位基因可能是子痫前期的遗传危险因子.ApoE ε4等位基因与高脂血症相关.     

子痫前期患者血清及胎盘组织中人类白细胞抗原G的表达研究

目的:检测正常晚期妊娠妇女及子痫前期患者胎盘组织HLA-G的表达及血清中sHLA-G的浓度,探讨HLA-G在子痫前期发病中的临床意义。方法:用半定量逆转录-聚合酶链技术(RT-PCR)检测37例正常晚期妊娠妇女(正常妊娠组)及41例子痫前期患者(轻度20例,重度21例)胎盘组织中HLA-G mRNA的表达;并用ELISA检测血清sHLA-G浓度。结果:(1)子痫前期胎盘组织中HLA-G mRNA表达水平分别为:轻度0.402±0.104、重度0.329±0.09,明显低于正常妊娠组的0.628±0.117(P<0.01),轻、重度差异亦有统计学意义(P<0.05)。(2)子痫前期血清sHLA-G浓度:轻度45.5±11.9u/ml,重度31.2±10.3u/ml,均明显低于正常妊娠组的105.7±12.5u/ml(P<0.01),轻重度差异亦有统计学意义(P<0.01)。(3)子痫前期患者血清sHLA-G浓度与胎盘组织HLA-G mRNA表达水平呈正相关(r=0.702,P<0.01)。结论:子痫前期血清sHLA-G浓度及胎盘组织中HLA-G表达水平均明显降低,可能与子痫前期发病及病情轻重程度相关。     

人类白细胞抗原G的表达与子痫前期发病的关系

目的 通过检测子痫前期孕妇相关组织中人类白细胞抗原G (HLA-G)的表达,探讨其与子痫前期发病的关系.方法 选择2009年3月至12月在陕西省妇幼保健院产科住院分娩的子痫前期孕妇30例,根据病情分为轻度子痫前期组8例,重度子痫前期组22例.选择同期健康孕妇30例为对照组.3组孕妇均以剖宫产方式分娩.采用ELISA法检测孕妇外周血、脐血及羊水中的可溶性HLA-G(sHLA-G)水平;采用蛋白印迹法检测胎盘、胎膜及脐带组织中HLA-G蛋白的表达.结果 (1)各组孕妇外周血、脐血、羊水中sHLA-G水平:轻、重度子痫前期组孕妇外周血sHLA-G水平分别为(50±14)、(30±6) μg/L,新生儿脐血中sHLA-G水平分别为(34±10)、( 26±8)μg/L,均明显低于对照组的(100±16)、(70±9) μg/L,分别与对照组比较,差异均有统计学意义(P＜0.01);重度子痫前期组与轻度子痫前期组比较,差异也有统计学意义(P＜0.01).重度子痫前期组新生儿脐血中sHLA-G水平虽低于轻度子痫前期组,但差异无统计学意义(P＞0.05).轻、重度子痫前期组孕妇羊水中sHLA-G水平分别为(26±7)、( 25±5) μg/L,均低于对照组的(27±6)μg/L,但分别与对照组比较,差异无统计学意义(P＞0.05);轻度子痫前期组与重度子痫前期组比较,差异也无统计学意义(P＞0.05).(2)各组孕妇胎盘、胎膜及脐带组织中的HLA-G蛋白表达:对照组胎盘组织中HLA-G蛋白表达水平为1.59±0.36,胎膜组织中表达水平为0.42±0.09,胎盘组织中的HLA-G蛋白表达水平明显高于胎膜组织,两者比较,差异有统计学意义(P＜0.05);对照组脐带组织中HLA-G蛋白表达水平为0.24±0.17,分别与胎盘及胎膜组织中的HLA-G蛋白表达水平比较,差异均有统计学意义(P＜0.01).轻度子痫前期组胎盘组织中HLA-G蛋白表达水平为0.78±0.21,重度子痫前期组为0.29±0.17,分别与对照组比较,差异均有统计学意义(P＜0.01).轻、重度子痫前期组孕妇胎膜及脐带组织中均未检测出HLA-G蛋白的表达.结论 与健康孕妇相比,HLA-G在子痫前期孕妇外周血、脐血及胎盘组织中呈明显低表达,HLA-G表达水平的异常可能与子痫前期的发病有关.     

人类白细胞相关抗原-G及其各亚型mRNA在正常妊娠及重度子痫前期患者胎盘组织中的表达

目的 研究人类白细胞相关抗原-G（HLA-G）及其各个亚型mRNA在正常妊娠及重度子痫前期患者胎盘组织中的表达.方法 选取2005-01-2005-06第四军医大学唐都医院10例重度子痫前期患者（研究组）及10例正常妊娠胎盘组织（对照组）,应用荧光定量RT-PCR比较两组间HLA-G及其各个亚型mRNA（HLA-G1、G2、G3、G4、G5、G6）的表达.结果 与对照组相比,重度子痫前期患者胎盘组织中总HLA-G mRNA显著降低,以HLA-G1、HLA-G3降低为主,差异有统计学意义（P＜0.05）.结论 HLA-G1与HLA-G3 在胎盘组织中的低表达可能与妊娠期高血压疾病的发病和病理生理过程有关.     

子(癎)前期患者血清TPA、HCG测定的对比意义

目的:探讨子癎前期患者及正常妊娠晚期妇女血清TPA、HCG的变化特点及临床意义。方法:将51例子癎前期患者设为实验组,分为轻度(A组)、重度(B组),33例正常晚孕者设为对照组,测定实验组、对照组TPA及HCG变化,并进行比较。结果:实验组TPA的浓度与对照组比较差异有显著性(P<0.05),实验B组与对照组比较差异有非常显著性(P<0.01),且与病情严重程度呈正相关;实验组HCG浓度与对照组比较差异有显著性(P<0.05)。实验A组与对照组比较差异非常显著(P<0.01)。结论:子癎前期患者外周血TPA增高与滋养细胞凋亡增加有关,而HCG分泌增加与缺氧状态下滋养细胞反应性增生有关,提示子癎前期患者有明显的滋养细胞增生与分化异常存在。TPA作为外周血滋养细胞凋亡的标志物,可间接反映胎盘功能的变化。     

人类白细胞抗原基因多肽性与不明原因反复流产免疫治疗妊娠结局的初步探讨

目的:探讨人类白细胞抗原(HLA)基因多态性对不明原因反复流产(URSA)免疫治疗疗效的预测价值。方法:①采用酶联免疫法(ELISA)测定URSA患者免疫治疗前、免疫治疗一疗程后封闭抗体(BA),并随访阳性者与阴性者的妊娠率。②采用52例封闭抗体阴性的URSA患者进行主动免疫治疗,随机抽取32例于免疫治疗前用SSP-PCR方法测定患者免疫治疗前及妊娠后血浆内的HLA-A、B、DR及G的表达率。结果:①免疫治疗后BA阳性者及阴性者的妊娠成功率差异无统计学意义,P>0.05。②HLA-G*010401及HLA*1502的表达频率在再次流产者中明显高于成功妊娠者,组间比较差异均有统计学意义(分别为P<0.01,P<0.05)。结论:HLA基因的多态性与免疫治疗妊娠结局似乎有更好的相关性,其中HLA-G*010401、HlA-DRB1*1502与免疫治疗后妊娠结局关系密切,有可能成为有价值的预测指标。     

Ca-ATPase Activity of Human Red Cell Ghosts: Preeclampsia,Lipid Peroxidation and MgSO4

The increased level of lipid peroxidation of red blood cells during preclampsia is considered to be responsible for the diminished Ca-ATPase activity in these cells. The level of lipid peroxidation and the Ca-ATPase activity of red blood cells from preeclamptic women, return to their normal values after in vivo and in vitro treatment with MgSO₄ for 24 h. In order to evaluate whether or not cell intactness is essential for these changes, we used either intact red blood cells or red cell ghosts from normotensive pregnant women. The intact red blood cells were treated with Fenton's reagent and then incubated with 4 mM MgSO₄. The red cells ghosts were irradiated with UV light and afterwards incubated with MgSO₄ at 4°C. Lipid peroxidation and Ca-ATPase activity were determined for all the preparations. Both, Fenton's reagent and UV irradiation increased the level of lipid peroxidation and diminished the Ca-ATPase activity of the red cell membranes. Incubation of the cells treated with Fenton's reagent, or the ghosts irradiated with UV, with 4 mM MgSO₄, returned Ca-ATPase activity and lipid peroxidation levels to normal values. The presence of MgSO4 blocked the effects in the ghosts of UV irradiation. MgSO₄ seems to better protect the red cell membrane against lipid peroxidation than other SO₄⁼ and Cl^? salts. These results indicate that the changes in the lipid peroxidation of the red cell ghosts and their Ca-ATPase activity are a result of changes to the cell membranes.     

Preeclampsia associates with RECK-dependent decrease in human trophoblasts migration and invasion

IntroductionPreeclampsia is characterized by reduced invasion capacity of trophoblasts involving lower matrix metalloproteinase (MMP) activity. Cell invasion is reduced by reversion-inducing-cysteine-rich protein with Kazal motifs (RECK), a plasma membrane protein that inhibits MMP in several cell types. However, it is unknown whether this mechanism happens in the human placenta from preeclampsia. The hypothesis of this study sustains that RECK expression is increased leading to reduced trophoblasts invasion in preeclampsia.MethodsRECK expression in the human first trimester trophoblast cell line HTR8/SvNeo and in placentas from normal (n = 4) and preeclampsia (n = 4) pregnancies was evaluated by Western blot and immunofluorescence. MMP-dependent gelatin hydrolyzation was measured by in situ zymography and gelatinase assay in placental and cell extracts. RECK was overexpressed (plasmidial vector transfection) or partially reduced (shRNA) to evaluate its role in HTR8/SVneo cell migration and invasion.ResultsRECK was expressed in trophoblasts layer in human placentas. Preeclampsia resulted in higher placental RECK protein abundance, reduced MMP function, and higher level of fibronectin (a MMP substrate) compared with placentas from normal pregnancies. RECK is also expressed in HTR-8/SVneo cells. Reduced RECK expression resulted in higher MMP-dependent gelatin hydrolyzation, associated to higher migration and invasion of HTR8/SVneo cells. However, RECK overexpression associated with reduced hydrolyzation, cell migration and invasion.DiscussionRECK is overexpressed in human trophoblasts from preeclampsia and may be responsible of this disease-associated lower migration and invasion of this cell type.     

人类白细胞相关抗原-G及其各亚型mRNA在正常妊娠及重度子前期患者胎盘组织中的表达

目的研究人类白细胞相关抗原-G(HLA-G)及其各个亚型mRNA在正常妊娠及重度子前期患者胎盘组织中的表达。方法选取2005-01-2005-06第四军医大学唐都医院10例重度子前期患者(研究组)及10例正常妊娠胎盘组织(对照组),应用荧光定量RT-PCR比较两组间HLA-G及其各个亚型mRNA(HLA-G1、G2、G3、G4、G5、G6)的表达。结果与对照组相比,重度子前期患者胎盘组织中总HLA-GmRNA显著降低,以HLA-G1、HLA-G3降低为主,差异有统计学意义(P<0.05)。结论HLA-G1与HLA-G3在胎盘组织中的低表达可能与妊娠期高血压疾病的发病和病理生理过程有关。     

The C825T Polymorphism in the G-protein Beta 3 Subunit Gene in Chinese Patients with Preeclampsia

Objectives:?The objective of the study was to investigate the relationship of a C825T polymorphism of the gene encoding the G protein β3 subunit with preeclampsia in a South-West Chinese population.?Results:?In the case-control study which included 221 preeclamptic case subjects and 277 normal control subjects the allele frequency of 825C→T in the GNB3 gene was 47.29% in patients with preeclampsia and 49.28% in the control group. Furthermore, there was no significant association between the polymorphism and blood pressure levels in the case or control group. However, it showed that the TT homozygotes (n = 39) in obese patients had higher diastolic blood pressure levels than CC homozygotes (n = 47) or CT heterozygotes (n = 84) during pregnancy (p < 0.05).?Conclusion:?Our work does not provide evidence in favor of GNB3 C825T being a candidate gene for conferring genetic susceptibility to preeclampsia in a South West Chinese population.     

Angiotensin-Converting Enzyme Insertion/Deletion (ACE I/D) and Angiotensin II Type 1 Receptor (AT1R) Gene Polymorphism and Its Association with Preeclampsia in Chinese Women

Objective: To investigate whether polymorphisms of angiotensin converting enzyme gene (ACE) and angiotensin II receptor type 1 gene (AT1R) are associated with etiology of preeclampsia and renal impact in women with preeclampsia. Methods: DNA was extracted from peripheral blood of 133 patients with preeclampsia and 105 healthy pregnant women. The I/D polymorphism of the ACE gene was assessed by polymerase chain reaction, and the A1166C polymorphism of the AT₁R gene was additionally assessed by DdeI digestion. The level of proteinuria, fasting serum urea, creatinine and uric acid were investigated according to different genotypes of ACE and AT1R genes. Results: The frequency of genotypes of the ACE gene and the AT1R gene was similar in preeclampsia and normal pregnancy. DD and ID genotype predominated in patients with severe proteinuria, as well as increased serum urea and uric acid. Serum creatinine was also increased, but no significant difference was found among three genotypes. The level of proteinuria, serum uric acid, urea, and creatinine did not vary between different AT1R genotypes. Compared with patients without renal dysfunction, the frequency of DD and ID genotypes of ACE gene was much higher in those with renal dysfunction, but AC and CC genotypes of AT1R gene were not. Conclusion: We found no association of the two gene polymorphisms with preeclampsia. However, ACE gene I/D polymorphisms were associated with the severe proteinuria and renal dysfunction seen in preeclampsia. Preeclampsia patients carrying the D allele may be susceptible to renal dysfunction.