孕妇血浆中sCD40及其配体与子痫前期发病及肾功能损害的关系

目的 探讨孕妇血浆中可溶性白细胞分化抗原(sCD40)和sCD40配体(sCD40L)水平变化与子痫前期发病及肾功能损害的关系.方法 选择2008年8月-2010年6月在青岛大学医学院附属医院产科分娩的轻度子痫前期孕妇28例(轻度子痫前期组),重度子痫前期孕妇35例(重度子痫前期组);另选同期妊娠结局良好的健康孕妇30例为对照组.比较3组孕妇分娩孕周及血压变化、血小板计数并检测其血常规、C反应蛋白(CRP)、尿常规、24h尿蛋白定量,以及血清尿酸(UA)、肌酐(Cr)、尿素氮(BUN)等生化指标.采用ELISA法检测3组孕妇血浆中sCD40和sCD40L的水平,并对血浆sCD40和sCD40L的水平与各临床指标的相关性进行分析.结果 (1)血常规及l临床指标:重度子痫前期组和轻度子痫前期组孕妇血浆CRP水平(分别为10.8及7.1 mg/L)均明显高于对照组(3.3 mg/L),前后两者分别比较,差异均有统计学意义(P＜0.05);重度子痫前期组高于轻度子痫前期组,两组比较,差异也有统计学意义(P＜0.05).重度子痫前期组孕妇分娩孕周(32.5周)明显低于轻度子痫前期组(37.2周)和对照组(38.6周),分别与对照组比较,差异均有统计学意义(P＜0.01);轻度子痫前期组与对照组比较,差异无统计学意义(P＞0.05).重度子痫前期组孕妇血小板计数(132×109/L)明显低于轻度子痫前期组(212×109/L)和对照组(216×109/L),分别比较,差异有统计学意义(P＜0.01);轻度子痫前期组与对照组比较,差异无统计学意义(P＞0.05).3组孕妇之间血红蛋白水平及白细胞数分别比较,差异均无统计学意义(P＞0.05).(2)血浆sCD40及sCD40L水平:重度子痫前期组、轻度子痫前期组和对照组孕妇血浆sCD40水平分别为133.6、126.5和90.7 ng/L,sCD40L水平分别为12.5、10.4和4.4 ng/L,24h尿蛋白定量分别为4.5、0.8 g和0,UA水平分别为486、289和162 μmol/L,重度子痫前期组以上各指标均明显高于轻度子痫前期组和对照组,差异均有统计学意义(P＜0.01);轻度子痫前期组也明显高于对照组,差异也有统计学意义(P＜0.01).重度子痫前期组孕妇血浆Cr(89 μmol/L)、BUN(5.32 mmol/L)水平高于轻度子痫前期组(分别为66μmol/L及4.49mmol/L)和对照组(分别为57 μmol/L及3.32 mmol/L),分别比较,差异均有统计学意义(P＜0.05);轻度子痫前期组与对照组比较,差异无统计学意义(P＞0.05).(3)相关性分析:轻、重度子痫前期组孕妇血浆sCD40水平与24 h尿蛋白定量呈正相关(r=0.434,P＜0.05),与UA、CRP呈明显正相关(r=0.536、0.528,P＜0.01),与收缩压、舒张压、分娩孕周、Cr、BUN、血小板计数无明显相关(r分别为0.135、0.183、-0.133、0.190、0.167、-0.221,P均＞0.05).轻、重度子痫前期组孕妇血浆sCD40L水平与24 h尿蛋白定量、UA、CRP均呈明显正相关(r分别为0.591、0.445、0.539,P均＜0.01),与收缩压、舒张压、分娩孕周、Cr、BUN、血小板计数无明显相关(r分别为0.178、0.212、-0.292、0.144、0.135、-0.273,P均＞0.05).轻、重度子痫前期组孕妇血浆sCD40L水平与sCD40呈明显正相关(r均为0.707,P＜0.01).对照组孕妇血浆sCD40、sCD40L水平与各项临床指标均无相关性(P＞0.05).结论 子痫前期孕妇血浆中sCD40和sCD40L水平明显升高,可能参与了子痫前期的发病,并导致肾功能损害.sCD40和sCD40L水平变化也与子痫前期的严重程度相关.

Abstract：

Objective To investigate the variance levels of plasma soluble leukocyte differentiation antigens CD40 (sCD40) and soluble CD40 ligand (sCD40L) in preeclamptic patients with renal damage and its relationship. Methods A total of 63 pregnant women attended the Department of Obstetrics, Affiliated Hospital of Qingdao University Medical College between August 2008 and June 2010. In the present study included 28 pregnant women with mild preeclampsia and 35 patients with severe preeclampsia. Thirty matched normotensive pregnant women were enrolled in the study as the control group. Expression of sCD40 and sCD40L were determined by ELISA. At the same time, the blood routine, C reaction protein ( CRP),urine routine, 24 hours urine protein excretion, and serum uric acid (UA), creatinine (Cr), blood urea nitrogen (BUN) were measured. The correlation analysis was performed between the sCD40/sCD40L and the blood biochemical indexes in 3 groups. Results ( 1 ) The median levels of CRP in severe preeclampsia (10. 8 mg/L)and mild preeclampsia group(7. I mg/L)are significantly higher than that of control group (3. 3 mg/L,P ＜ 0. 05 ); The level of CRP in severe preeclampsia group was also higher than that of mild preeclampsia group ( P ＜ 0. 05 ). The median gestational age at delivery in severe preeclampsia ( 32. 5 weeks)was significantly less than that of mild preeclampsia group ( 37. 2 weeks) and normal group ( 38. 6 weeks,P ＜ 0. 05). However no significant differences were observed between mild preeclampsia group and normal group ( P ＞0. 05 ). The platelet count in severe preeclampsia ( 132 × 109/L) was significantly less than those of mild preeclampsia group (212 × 109/L) and normal group ( 216 × 109/L, P ＜ 0. 01 ), but no significant differences were observed in blood platelet amount between mild preeclampsia group and normal group ( P ＞0. 05 ). There was no significant difference in hemoglobin level and white blood cell in three groups ( P ＞0. 05). (2) The sCD40 plasma concentration in severe, mild preeclampsia and normal group was 133.6,126. 5 and 90. 7 ng/L, respectively. The sCD40 L plasma concentrations were 12. 5, 10. 4 and 4. 4 ng/L respectively in the 3 groups. 24 hours urinary protein quantitative was 4. 5 g/d,0. 8 g/d and 0 in the 3 groups respectively. And the UA level was 486 μ mol/L,289 μmol/L and 162 μmol/L. In the above three groups,the monitoring indicators were significantly higher in women with severe preeclampsia group compared with mild preeclampsia and control groups (P ＜ 0. 01 ), and there were also higher in mild preeclampsia group than that in control groups ( P ＜ 0. 01 ). The level of plasma Cr ( 89 μmol/L) and BUN ( 5. 32 mmol/L) in severe preeclampsia group were higher than those of mild preeclampsia group (66 μmol/L and 4. 49mmol/L) and control group ( 57 μmol/L and 3.32 mmol/L, P ＜ 0. 05 ). There was no significant difference between mild preeclampsia group and normal group (P ＞ 0. 05 ). (3) The correlation analysis indicated that the level of sCD40 has a positive correlation with 24 hours urinary protein quantitative( r = 0. 434, P ＜ 0. 05 ),also significant positive correlation( r =0. 536,0. 528 ,P ＜ 0. 01 ) between the level of sCD40 and UA or CRP in women with preeclampsia. There was no significant correlation between the level of sCD40 and systolic blood pressure, diastolic blood pressure, delivery gestational age, Cr, BUN, and platelet count(r =0. 135,0. 183, -0. 133,0. 190,0. 167, -0. 221 ,all P ＞0. 05 ). There were positive correlation between the level of sCD40L and 24 hours urine protein excretion, either UA or CRP( r =0. 591,0. 445,0. 539 ,all P ＜0. 01 ). No significant correlation was found between sCD40 L and systolic blood pressure, diastolic blood pressure,delivery gestational age, Cr, BUN, and platelet count( r =0. 178,0. 212, -0. 292,0. 144,0. 135, -0. 273,all P ＞0. 05). There was significant positive correlation between plasma sCD40 and sCD40L ( r =0. 707 ,P ＜0. 01 ). There was no relationship between the level of sCD40, sCD40L and the blood biochemical indexes in normotensive pregnant women ( P ＞ 0. 05 ). Conclusions The plasma concentrations of sCD40 and sCD40 L are significantly higher in pregnant women with preeclampsia compared with the control, which may be involved in the development of preeclampsia and contribute to the kidney damage. The variance levels of sCD40 and sCD40L may be also related to the severity of preeclampsia.     

褪黑素抑制氧化应激和铁死亡缓解妊娠糖尿病大鼠病理损伤

目的:探讨褪黑素对妊娠糖尿病(GDM)大鼠的治疗作用及可能作用机制。方法:将24只雌性大鼠分成4组正常妊娠组、GDM模型组、低剂量褪黑素5mg/(kg·d)治疗组及高剂量褪黑素10mg/(kg·d)治疗组,每组6只。不同剂量褪黑素治疗14天后,检测大鼠胰腺组织形态病理变化及细胞凋亡水平,检测血清生化指标、细胞氧化应激指标及铁含量。检测胰腺组织中褪黑素受体基因及铁死亡通路相关基因的mRNA和蛋白表达水平。结果:褪黑素治疗明显减轻了大鼠胰腺组织病理损伤和细胞凋亡水平,降低了血清中葡萄糖、糖化血红蛋白及胰岛素水平,显著升高了胰腺组织中CAT、GSH-PX、SOD等抗氧化酶活性及抗氧化剂GSH水平,降低了H2O2、MDA及铁含量。褪黑素治疗显著增加了大鼠胰腺中褪黑素受体基因MTNR1B表达,同时调控铁死亡通路相关基因表达,包括增加GPX4及FTH1基因表达水平,降低ACSL4基因表达水平。结论:褪黑素可能通过褪黑素受体介导,抑制组织氧化还原水平失衡,降低组织细胞凋亡和铁死亡,进而缓解GDM所致的病理损伤。     

MMIF—rs755622位点单核苷酸基因多态性与子痫前期发病关系

目的研究巨噬细胞移动抑制因子（MMIF）-rs755622位点单核苷酸基因多态性与子痫前期发病的关系。方法选取子痫前期孕妇165例,分为轻度（72例）和重度子痫前期组（93例）。另选同期正常孕妇120例为对照组。采用聚合酶链限制性片段长度多态性（PCR—RFLP）方法对该位点进行基因分型,比较各组基因型频率和等位基因频率的差异。测定各组空腹血糖（FBG）、空腹胰岛素（FIN）水平,计算稳态模型胰岛素抵抗指数（HOMA—IR）;比较不同基因型在各组内FBG、FIN以及HOMA-IR的差异。结果MMIF-rs755622位点共检出GG、GC和CC等3种基因型。子痫前期组与对照组比较,基因型频率与等位基因频率差异无显著性（P〉0．05）。轻度、重度子痫前期组间基因型频率与等位基因频率比较差异也无显著性（P〉0．05）。轻度子痫前期组与重度子痫前期组内GC和CC基因型孕妇FIN及HOMA—IR均高于GG基因型孕妇,差异均有显著性（t=3．17～9．74,P〈0．05）。结论MMIF—rs755622位点单核苷酸基因多态性与子痫前期IR密切相关,CG和CC基因型加重了子痫前期IR的程度,但该位点可能不是中国汉族子痫前期孕妇发病的易感位点     

妊娠高血压综合征病人治疗前后脐动脉血流变化的超声检测

①目的　探讨彩色多普勒超声对妊娠高血压综合征病人治疗前后脐动脉血流变化的检测价值。②方法　采用动脉脐血流检测仪对 6 0例正常妊娠妇女及 6 0例妊娠高血压综合征孕妇治疗前后的脐动脉血流收缩期与舒张期峰值比值 (S/D)、阻力指数 (RI)进行检测。③结果　妊娠高血压综合征病人治疗前S/D、RI明显高于正常妊娠妇女 (t=4 .97、19.78,P <0 .0 1) ,治疗后S/D、RI值较治疗前明显降低 ,差异有极显著性 (t=2 .34、18.34,P <0 .0 1) ,与正常对照组比较差异无显著性 (t=1.0 6、1.6 1,P >0 .0 5 )。④结论　彩色多普勒超声对妊娠高血压综合征病人治疗前后脐动脉血流变化具有一定的检测价值 ,对评估胎儿宫内状况、预测围产儿预后有重要临床参考价值     

IL-10、IL-8在习惯性流产患者外周血及母胎界面中的表达

目的：研究IL-10、IL-8的免疫调节机制在习惯性流产患者中的作用。方法：用酶联免疫方法测定30例正常早孕妇女、30例习惯性流产患者血清及绒毛、蜕膜组织中IL-10、IL-8的表达水平。所有研究对象均排除全身或感染性疾病。结果：同正常早孕妇女相比，习惯性流产患者血清及绒毛、蜕膜组织中IL-8水平明显增岛（P〈0．01），IL-10水平明显降低（P〈0．01）；母胎界面中IL-10、IL-8因子的表达与外周血中的表达呈正相关。结论：正常妊娠分泌IL-10升高，当孕妇分泌IL-8升高而IL-10降低时，可能导致习惯性流产的发生。     

氧化低密度脂蛋白及其受体对滋养细胞凋亡的影响

目的:探讨氧化低密度脂蛋白(oxLDL)及血凝集素样氧化低密度脂蛋白受体1(LOX-1)对滋养细胞凋亡的影响。方法:采用蛋白印迹法检测滋养细胞LOX-1蛋白的表达;RT-PCR技术检测LOX-1mRNA及caspase-3mRNA的表达;流式细胞仪检测滋养细胞凋亡指数。结果:不同浓度oxLDL(0.01,0.05,0.10mg/ml)培养下细胞滋养细胞中LOX-1蛋白、mRNA及caspase-3mRNA表达水平均明显高于对照组(P<0.01),各组间比较差异均有统计学意义(P<0.01)。拮抗剂组LOX-1蛋白、mRNA及caspase-3mRNA表达水平均显著低于同浓度oxLDL刺激组,差异亦有统计学意义(P<0.01)。结论:oxLDL可通过上调滋养细胞中LOX-1表达引起滋养细胞的过度凋亡。     

远程胎儿监护用于妊娠期糖尿病的产前监测

目的探讨远程胎儿监护网络在妊娠期糖尿病(GDM)产前监测的临床价值。方法采用远程胎儿监护网络,对50例GDM孕妇进行产前无负荷试验(NST)监测(试验组),同期随机选择常规胎动计数和定期到医院进行NST检查的GDM孕妇50例作为对照(对照组),分析两组胎儿监护结果和妊娠结局。结果试验组NST异常率(34.6%)较对照组(25.5%)显著增加(P<0.05)。试验组(9.58±0.77)新生儿Apgar评分高于对照组(8.70±1.23)(P<0.05)。试验组新生儿窒息和早产儿的发生率分别为12.0%和8.0%,低于对照组的24.0%和22.0%(P<0.05)。两组剖宫产率的差异无显著性(P>0.05)。结论利用远程胎儿监护进行GDM产前监测,可改善围产儿预后,是GDM孕妇自我监护的新选择。     

妊娠期缺乏维生素D可能会引起的损害

有证据显示,维生素D缺乏促成大量常见慢性疾病的发病风险增加,作用机制不同于经典的作用于体内骨钙平衡.通过维生素D受体,维生素D可以产生一系列有利的生物作用,保持人类身体健康.我们假设有些作用在妊娠期间是至关重要的.该文章的中心是叙述关于维生素D在妊娠期的经典的和非经典的作用.它提及妊娠期缺乏维生素D与子痫前期、抗胰岛素性及妊娠期糖尿病发病风险的增加有潜在的联系.     

BACs-on-Beads技术联合染色体核型分析在高龄孕妇产前诊断中的应用

目的 探讨染色体核型分析和BACs-on-Beads(BoBs)技术在高龄孕妇产前诊断中的临床应用价值。方法 选取2017年1月至2021年4月在新长安妇产医院进行产前诊断的1033例高龄孕妇羊水细胞行染色体核型分析和BoBs检测，结果进行分析比较。若遇微缺失/微重复病例，染色体微阵列技术（CMA）提供进一步验证。结果 1033例高龄孕妇中，共检出染色体异常103例，异常检出率为9.97%，其中染色体核型分析检出101例，BoBs检出100例，高龄合并无创产前检测高风险的检出率最高，为70.41%。103例异常核型中，21三体73例，18三体12例，13三体1例，47,XXX 4例，47,XYY 3例，45,X 1例，47,XXY 3例，性染色体嵌合1例，BoBs检测结果与染色体核型分析结果一致；BoBs检出22q11.2微重复综合征1例，Smith-Magenis综合征1例，与CMA检测结果一致，染色体核型分析未检出；染色体核型分析检出结构异常3例，BoBs未检出。结论 “染色体核型分析+BoBs”的产前诊断模式可广泛应用于高龄孕妇，在提高检测效率的同时减少染色体异常胎儿的出生风险。