Plasma Nogo-A and placental growth factor levels are associated with portal hypertension in patients with liver cirrhosis

BACKGROUND Clinically significant portal hypertension(CSPH) and severe portal hypertension(SPH) increase the risk for decompensation and life-threatening complications in liver cirrhosis. Pathologic angiogenesis might contribute to the formation of these conditions. Placental growth factor(PlGF) and Nogo-A protein are biomarkers of pathological angiogenesis, but data on their role in liver cirrhosis and portal hypertension is scarce.AIM To determine plasma levels of PlGF and Nogo-A in patients with liver cirrhosis,CSPH, SPH and potential to predict portal hypertension.METHODS A cohort of 122 patients with hepatitis C virus and/or alcohol-induced liver cirrhosis with characterized hepatic venous pressure gradient(HVPG) were included in the study. Demographic data, medical history, Child-Turcotte-Pugh and Model of End Stage liver disease score, clinical chemistry, liver stiffnessvalues were recorded on the day of the procedure prior HVPG measurement. The degree of portal hypertension was determined by the invasive HVPG measurement. Nogo-A and PlGF plasma levels were evaluated using enzyme linked immunosorbent assay. The control group consisted of 30 healthy age-and sex-matched individuals.RESULTS Peripheral PlGF levels were higher and Nogo-A levels were lower in patients with liver cirrhosis(23.20 vs 9.85;P < 0.0001 and 2.19 vs 3.12;P = 0.004 respectively). There was a positive linear correlation between peripheral levels of PlGF and HVPG(r = 0.338, P = 0.001) and negative linear correlation between the peripheral Nogo-A levels and HVPG(r =-0.267, P = 0.007). PlGF levels were higher in CSPH and SPH(P = 0.006;P < 0.0001) whereas Nogo-A levels were lower(P = 0.01;P < 0.033). Area under the curve for the diagnosis of CSPH for PlGF was 0.68(P = 0.003) and for Nogo-A-0.67(P = 0.01);for SPH 0.714(P <0.0001) and 0.65(P = 0.014) respectively. PlGF levels were higher and Nogo-A levels were lower in patients with esophageal varices(P < 0.05). PlGF cut-off value of 25 pg/mL distinguished patients with CSPH at 55.7% sensitivity and76.7% specificity;whereas Nogo-A cut-off value of 1.12 ng/mL was highly specific(93.1%) for the diagnosis of CSPH.CONCLUSION Plasma PlGF levels were higher while Nogo-A levels were lower in patients with liver cirrhosis and portal hypertension. Biomarkers showed moderate predictive value in determining CSPH and SPH.

Inhibitory effect on subretinal fibrosis by anti-placental growth factor treatment in a laser-induced choroidal neovascularization model in mice

AIM:To investigate whether anti-placental growth factor(PGF) can inhibit subretinal fibrosis and whether this effect is mediated by the inhibitory effect of PGF on epithelial-mesenchymal transition(EMT) of retinal pigment epithelial(RPE) cells.METHODS:Subretinal fibrosis model was established in laser induced choroidal neovascularization(CNV) mice on day 21 after laser photocoagulation.Immunofluorescence staining(IFS) of cryosections and enzyme-linked immunosorbent assay(ELISA) were used to detect the expression of PGF.IFS of whole choroidal flat-mounts was used to detect the degree of subretinal fibrosis.IFS of cryosections and ELISA were used to detect the expression of EMT related indicators in subretinal fibrosis lesions.RESULTS:The expression of PGF protein in subretinal fibrosis lesions was significantly up-regulated(P<0.05),and mainly co-stained with pan-cytokeratin labeled RPE cells.Intravitreal injection of anti-PGF neutralizing antibody reduced the area of subretinal fibrosis and the ratio of fibrotic/angiogenic area significantly at the concentrations of 0.25,0.5,1.0,and 2.0 μg/μL(all P<0.05).The expression of E-cadherin in the local RPE cells decreased,while α-SMA increased significantly in subretinal fibrosis lesions,and the application of anti-PGF neutralizing antibody could reverse these changes(P<0.05).CONCLUSION:The expression of PGF is up-regulated in the lesion site of subretinal fibrosis and mainly expressed in RPE cells.Intravitreal injection of anti-PGF neutralizing antibody can significantly inhibit the degree of subretinal fibrosis in CNV mice,and this effect may be mediated by the inhibition of PGF on EMT of RPE cells.

Analysis of Placental Growth Factor in Placentas of Normal Pregnant Women and Women with Hypertensive Disorders of Pregnancy

To investigate the expressions of placental growth factor （PLGF） in placenta with hypertensive disorders of pregnancy （ HDP）, 45 women with HDP and 20 normally pregnant women were studied. Among 45 women with HDP, there were 23 cases of severe preeclampsia and one case of eclampsia. The location and level of PLGF proteins was determined by immunohistochemistry and Western blot. The expression of PLGF mRNA in placenta was assessed by reverse transcriptionalpolymerase chain reaction （RT-PCR）. The results showed that： （1） The distribution of PLGF in placenta with HDP was similar to normal one, which was mainly in the cytoplasm of villous syncytiotrophoblast and villous stroma; （2） The expression of PLGF protein was significantly decreased in placentas with mild and severe preeclampsia compared to the normal ones （0.3±0.4 vs 0.6± 0.4, 0.2±0.5 vs 0. 6±0. 4, P〈0.01）. There were no differences between the gestational hypertension placenta and normal one （0.5±0.6 vs 0. 6±0. 4, P〉0.05） ; （3） The transcription levels of the PLGF mRNA in placentas with preeclampsia were significantly lower than in normal groups （3.33±0.39 vs 4.87±0. 60, 1.97±0.29 vs 4.87±0.60, P〈0.01）, and no differences were found between the gestational hypertension placenta and normal groups. These findings suggest that the abnormal expression of PLGF in placentas is related to the pathogenesis of HDP.

Effect of Compound Danshen Injection Combined with Labetalol on Liver Function and Placental Growth Factor in Patients with Eclampsia

Objective: To explore the effect of Compound Danshen Injection combined with Labetalol on liver function and placental growth factor in patients with eclampsia. Methods: Seventy patients with eclampsia who were treated in the Hospital from February 2017 to February 2019 were enrolled. The patients were divided into two groups according to the random number table, with 35 cases in each group. The Observation group was treated with Labetalol, and the combined therapy group was treated with Compound Danshen Injection combined with Labetalol. The liver function [alanine aminotransferase, aspartate aminotransferase, total protein, and albumin], hemorheology indicators, placental growth factor and serum insulin-like growth factor-1 and clinical indicators in the two groups were analyzed. Results: After treatment, the levels of alanine aminotransferase and aspartate aminotransferase in the combined therapy group were significantly lower than those in the Observation group. The levels of total protein and albumin in the combined therapy group were significantly higher than those in the Observation group (P<0.05). After treatment, the high-cut and low-cut whole blood viscosity, plasma viscosity and erythrocyte rigidity index in the combined therapy group were significantly lower than the Observation group, and the difference was statistically significant (P<0.05). After treatment, the levels of PLGF and IGF-1 in the combined therapy group were significantly higher than those in the Observation group, and the difference was statistically significant (P<0.05). After treatment, the gestational age, neonatal weight index, placental weight and neonatal 1 min Apgar score in the combined therapy group were significantly higher than the Observation group, and the difference was statistically significant (P<0.05). Conclusion: For patients with eclampsia, Compound Danshen Injection combined with Labetalol is with great safety, which can help stabilize their condition, and improve their liver function and placental growth factor status.

Associations between Placental Insulin-Like Growth Factor-1 Gene Expression, DNA Methylation and Intrauterine Growth Restriction

Intrauterine growth restriction (IUGR) is a common fetal development disorder which has great impact on neonatal health. Insulin-like growth factor-1 (IGF1) has an important role in regulating fetal growth. Whether IGF1 DNA methylation was associated with IUGR has not been studied. Placenta samples from IUGR (n = 27) and normal delivery (n = 29) were collected whereas basic information of mothers and infants were also collected. RT-PCR was performed to examine IGF1 transcriptions and bisulfite sequencing PCR was used for DNA methylation analysis. Gene expression analysis found IUGR had significantly lower IGF1 transcription compared to control group (IUGR: 0.330 ± 0.351;control group: 1.001 ± 0.800, t = 3.995, P IGF1 were all highly methylated and there is no difference on DNA methylation rate between IUGR and control group (IUGR: 75%;control group: 81%;P = 0.09). Interestingly, in both IUGR and control groups, male fetus had significantly higher methylation rate than female fetus (IUGR: male: 87%;female: 74%, P = 0.016;control: male: 82%;female: 69%, P = 0.012). There was no correlation between IGF1gene expression and DNA methylation rate (r = 0.095, P = 0.063). Intrauterine fetal growth restriction placenta had significantly lower IGF1gene expression;however, IGF1 DNA methylation level was similar. A potential fetus gender difference was also found in IGF1 DNA methylation rate.

Effect of Bushen Yiqi Huoxue Recipe on Placental Vasculature in Pregnant Rats with Fetal Growth Restriction Induced by Passive Smoking

Interactions of vascular endothelial growth factor （VEGF） with receptors VEGFR1/Fltl and VEGFR2/Flk1, and those of angiopoietins （Ang-1, Ang-2） with receptor Tie2 play important roles in placental angiogenesis. This study investigated vascular morphology and expression of these angiogenic factors in rat placenta on the day 15, 18, 21 of gestation （D 15, D 18 and D21）. The rats were randomly assigned into 3 groups： normal group, model group [fetal growth restriction （FGR） model], and Bushen Tqi Huoxue （BYHR） recipe treatment group （BYHR group, the pregnant rats with FGR were treated with BYHR recipe）. Morphological analysis indicated that during initial villous formation, fetal nucle- ated erythrocytes （FNEs） appeared in maternal blood sinus （MBS）. Subsequently, FNEs were sur- rounded by endothelial cells to form fetal capillary （FC） and then by trophoblast cells to form villi. As pregnancy proceeded, FC density increased progressively with increasing endothelial identification staining （EIS） in normal and BYHR groups. Whereas, villous formation was suppressed, normal in- crease in FC density was impaired and EIS was weakened in model group. Quantitative PCR analysis showed that VEGF and Flkl mRNA increased over gestation in all groups, indicating that VEGF might play a pivotal role in FC growth during late gestation. VEGF mRNA was increased on D15, while de- creased on D21 in model group as compared with normal group and BYHR group. Immunohistochemi- cally, Ang-2 protein was highly expressed in FNEs, gradually disappeared as villi matured, and decreased over gestation in all groups, indicating that Ang-2 might play a pivotal role in villous formation, which was further supported by decreased Ang-2 mRNA and protein expression in model group on D 15. Ang-1 mRNA, Tie2 mRNA and Ang-1/Ang-2 ratio increased from D15 to D18 in all groups as placenta matured. Ang-1 mRNA, Tie2 mRNA and Ang-1/Ang-2 ratio were decreased on D18 in model group as compared with normal and BYHR groups, indicating delayed maturity of FGR placenta. Alterations in angiogenic factors may result in altered placental vasculature and cause placental insufficiency. BYHR recipe could balance the angiogenic factors to promote the formation and maturation of FGR placental vasculature.

IMMUNOHISTOCHEMICAL LOCALIZATION OF EPIDERMAL GROWTH FACTOR RECEPTOR AND C-erbB-2 ONCOGENE PRODUCT IN DEVELOPING HUMAN PLACENTA

Cytologic locailzation of epidermai growth factor receptor (EGF-R) and C-erbB2oncogene product in normal developing placenta ovas studied by avidin/biotin immunoperoxidase techniques.Both proteins were predominantly expressed in the villous syncytiotrophoblasts but not in the cytotrophoblasts.The immunoreactive intensity for EGF-R decreased with the development of pregnancy.Concerning the intermediate trophoblasts in cell islands and cell columns,both proteins were more easily detected in the cells distal to the villous stroma than in the juxtastromal cells.These findings suggest that EGF-R and C-erbB-2 may play a significant role in the induction and regulation of differentiated trophoblast function

Placenta Growth Factor and Soluble Fms-Like Tyrosine Kinase 1 in Preeclampsia and Normotensive Pregnant Nigerian Women

Background: Preeclampsia (PE) is still one of the leading causes of maternal/perinatal morbidity/mortality in Nigeria. Imbalance between placenta growth factor (PLGF) and soluble fms-like tyrosine kinase 1 (sFlt1) has been reportedly present both before and after the manifestation of PE;however, Nigerian data regarding these angiogenesis-related substances are lacking. We here attempted to determine the maternal serum level of PLGF and sFlt1 and sFlt1/PLGF ratio in PE vs. non-PE women in Lagos State University Teaching Hospital, Nigeria. Methods: An observational cross-sectional study was made on 75 women with PE and 75 age-gestational-age matched women without PE, as case and control, respectively. Levels of sFlt-1, PIGF and the sFlt-1: PIGF ratio was compared between the two. Results: Serum levels of Flt-1 and sFlt1/PIGF ratio were significantly higher in PE patients (6581.86 ± 865.75, and 146.42 ± 92.43) than in the normotensive control (4584.52 ± 1479.6 and 11.60 ± 6.42). PIGF was significantly lower in PE patients (70.14 ± 51.03) than the normotensives (494.06 ± 475.8). There were positive and negative correlations between the sFlt-1 and PLGF respectively and mean arterial blood pressure. Conclusion: Serum sFlt-1, sFlt1/PIGF ratio was significantly higher and PIGF levels were significantly lower in PE than normotensive control in Nigerian population.

血清sFT-1、PIGF对子痫前期患者妊娠结局的预测价值

目的 探讨血清可溶性血管内皮生长因子受体1(sFlt-1)、胎盘生长因子(PIGF)水平对子痫前期(PE)患者妊娠结局的预测价值。方法 选取PE孕妇136例(其中轻度PE 94例,重度PE 42例)和健康孕妇100例(对照组),均行血清sFlt-1、PIGF检测,比较两组血清sFlt-1、PIGF水平差异。按是否发生不良妊娠结局,将PE产妇分为结局不良组(n=54)与结局良好组(n=82),比较不同妊娠结局组血清sFlt-1、PIGF水平差异,使用受试者工作特征(ROC)曲线评价sFlt-1、PIGF对不良妊娠结局的预测能力。结果 PE组与对照组比较,血清PIGF水平显著下降(P<0.05),sFlt-1增高(P<0.05);且重度PE组血清PIGF水平低于轻度PE组(P<0.05),sFlt-1高于轻度PE组(P<0.05)。与结局良好组比较,结局不良组收缩压、24 h尿蛋白定量及血清sFlt-1水平更高(P<0.05),PIGF水平更低(P<0.05)。Logistic回归模型分析得出,血清sFlt-1(OR=1.861)及PIGF(OR=0.654)均为PE产妇不良妊娠结局的独立影响因素(P<0.05)。ROC曲线分析显示,血清sFlt-1、PIGF预测不良妊娠结局的AUC分别为0.857、0.855。结论 血清sFlt-1、PIGF与PE的发生发展相关,且对PE孕妇不良妊娠结局有一定的预测价值。

PIGF、sVEGFR-1、NO联合PI对高危孕妇发生子痫前期的预测

【目的】探讨血清胎盘生长因子（PIGF）、可溶性血管内皮生长因子受体-1（s VEGFR-1）、一氧化氮（NO）浓度联合子宫动脉搏动指数（PI）在高危孕妇中预测子痫前期发生的价值。【方法】收集162例具有子痫前期高危因素孕妇妊娠22~26周时的血清标本,应用酶联免疫吸附试验（ELISA）检测PIGF及s VEGFR-1浓度,比色法检测NO浓度,同期行子宫动脉多普勒超声检查测定PI值。【结果】134例孕妇发生子痫前期（子痫前期组）,128例孕妇血压始终维持正常（血压正常组）。2子痫前期组孕妇血清中PIGF、s VEGFR-1、NO水平及PI分别为（264±116）pg/m L、（4823±1562）pg/m L、（57±28）μmol/L、2.7±0.1;血压正常组分别为（418±130）pg/m L、（1102±158）pg/m L、（107±28）μmol/L、2.2±0.2。两组比较,差异均有统计学意义（P〈0.001）。3单一参数预测子痫前期的敏感度和特异度Pl GF为78.0%和80.7%（切割值为286.3 pg/m L时）,s VEGFR-1为81.2%和83.5%（切割值为2 005.0 pg/m L时）,NO为75.2%和80.0%（切割值为50.9μmol/L时）,PI为79.6%和86.2%（切割值为2.31时）。联合4项参数阳性值预测子痫前期的敏感度和特异度为92.7%和95.6%,均高于单一参数（P〈0.001）。血清PIGF、s VEGFR-1、NO的浓度与母亲的妊娠结局显著关联（P〈0.001）。【结论】血清PIGF、s VEGFR-1、NO浓度联合PI在孕22~26周的高危孕妇中预测子痫前期的发生有较好的临床价值。

肺癌患者血清bFGF和PIGF检测的临床意义

目的探讨胎盘生长因子(PIGF)和碱性成纤维细胞生长因子(bFGF)在肺癌患者血清中的表达及其与临床病理特征的关系。方法通过酶联免疫吸附法(ELISA)分别检测136例肺癌患者和68例正常对照者血清中PIGF、bFGF的表达水平,分析两者表达的相关性及其与临床病理特征的关系。结果肺癌组患者血清中PIGF和bFGF的表达水平分别为(528.26±27.54)pg/ml和(835.45±7.83)pg/ml,明显高于正常对照者的(482.45±13.23)pg/ml和(192.18±7.65)pg/ml(P<0.05)。肺癌患者血清PIGF和bFGF的表达水平与年龄、性别、病理分型无明显的相关性(P>0.05),而与肿瘤的分化程度、TNM分期、远处转移均相关(P<0.05)。经Pearson相关性检验,肺癌患者血清中bFGF和PIGF的表达水平呈正相关(r=0.517,P<0.05)。结论 PIGF和bFGF可能参与肺癌的发生、发展、侵袭和转移过程,能够反映疾病进展的情况。

妊娠期糖尿病并发子痫前期患者血清Lipocalin-2、sFlt-1、PIGF水平及临床意义

目的检测妊娠期糖尿病并发子痫前期患者血清Lipocalin-2、可溶性血管内皮生长因子受体1(s Flt-1)、胎盘生长因子(PIGF)水平,并探讨其临床意义。方法选取2013年3月至2015年6月定期孕前检查并住院分娩的单胎妊娠的孕妇212例作为研究对象。并将其分为妊娠期糖尿病并发子痫前期组(GDM-PE组)45例,妊娠期糖尿病组(GDM组)55例,子痫前期组(PE组)52例,正常孕妇60例(对照组)。然后用酶联免疫吸附法(ELISA)检测各组Lipocalin-2及s Flt-1、PIGF水平。结果四组研究对象的年龄、孕周及孕前BMI比较,差异均无统计学意义(P>0.05)。GDM-PE组孕期BMI、收缩压、舒张压等各项指标均大于GDM组和对照组(P<0.05)。PE组和GDM-PE组孕期BMI、收缩压、舒张压等各项指标均大于GDM组和对照组(P<0.05)。ELISA检测结果显示:和对照组相比,Lipocalin-2在GDM、PE及GDM-PE组表达水平均升高(P<0.05),GDM-PE组Lipocalin-2表达高于GDM组和PE组(P<0.05);s Flt-1表达在GDM、PE及GDM-PE组均高于对照组(P<0.05),在PE及GDM-PE组均高于GDM组(P<0.05);PIGF表达在GDM、PE及GDM-PE组均低于对照组(P<0.05)。结论血清Lipocalin-2和s Flt-1水平在GDM-PE患者中会明显升高,而PIGF水平则会明显降低,其原因可能与胰岛素抵抗和内皮细胞损伤有关。三个指标联合应用于早期预测GDM-PE疾病具有一定的临床意义。

外周血miR-152、PIGF、sFlt-1和sEng水平对子痫前期患者不良孕产结局的预测分析

目的探讨子痫前期(PE)患者血清中微小RNA152(miR-152)、胎盘生长因子(PIGF)、可溶性血管内皮生长因子(sFlt-1)及可溶性内皮抑素(sEng)表达水平对不良孕产结局的诊断预测价值。方法选取西安医学院第一附属医院2019年1月至2020年12月收治的145例PE患者为研究对象,其中发生不良孕产结局者为研究组(n=60),未发生不良孕产结局者为对照组(n=85),绘制受试者工作特征(ROC)曲线、计算曲线下面积(AUC)分析预测价值。结果本研究145例PE患者中发生不良孕产结局的患者为60例(41.38%),其中早产40例(66.67%)、胎盘早剥5例(8.33%)、胎儿窘迫12例(20.00%)、低出生体重儿44例(73.33%)、胎死宫内1例(1.67%)、新生儿肺炎13例(21.67%);研究组患者孕周和胎儿出生体重小于对照组,差异有统计学意义(t/H值分别为7.58、11.29,P<0.05),两组间年龄和住院天数差异无统计学意义(P>0.05);与对照组相比,研究组患者miR-152、sFlt-1、sEng的表达水平上升,PIGF水平下降,差异均具有统计学意义(t/H值分别为-7.73、-3.62、-5.18、4.06,P<0.05);单独指标诊断PE患者发生不良孕产结局时,miR-152诊断AUC最大,为0.80;联合指标诊断时,AUC为0.89,特异性为86.23%,敏感性为77.47%。结论PE患者血清中PIGF、sFlt-1和sEng水平联合miR-152检测,对于PE患者发生不良孕产结局的预测诊断具有一定临床价值。

子痫前期患者孕早期PAPP-A、PIGF及25(OH)D3水平与疾病相关性研究

目的研究妊娠相关血浆蛋白A(PAPP-A)、胎盘生长因子(PIGF)及25-羟维生素D3[25-(OH)D3]对子痫前期(PE)的预测价值。方法分析2018年3月至2020年3月在本院分娩的1 200例单胎妊娠孕妇的临床资料。其中正常者1 122例(正常组),PE者78例(PE组,重度PE者29例,轻度PE者49例),比较两组及不同病情PE患者PAPP-A、PIGF及25(OH)D3水平,分析上述因子与PE病情相关性。结果 PE组PAPP-A、PIGF、25(OH)D3均显著低于正常组,差异有统计学意义(P<0.05)。随着PE患者病情进展,PAPP-A、PIGF及25(OH)D3水平逐渐降低(P<0.05)。相关性分析结果显示,血清PAPP-A、PIGF及25(OH)D3与PE病情严重程度均呈负相关(P<0.05)。结论妊娠早期孕妇PAPP-A、PIGF及25(OH)D3水平下降可能与PE发生、发展有关,通过检测上述因子可有效评估PE病情。

血清sFlt-1、PIGF和补体系统激活因子水平预测孕中期孕妇子痫前期发病的价值

目的探讨血清可溶性胎盘血管内皮生长因子受体-1(sFlt-1)、胎盘生长因子(PIGF)和补体系统激活因子水平预测孕中期(20~26周)孕妇子痫前期(PE)发病的价值。方法选取2018年6月至2020年6月嘉兴市妇幼保健院产科就诊的至少有1项PE危险因素的孕中期孕妇300例,将发展为PE的46例设为发病组,剩下254例设为未发病组。比较两组孕妇sFlt-1、PIGF、sFlt-1/PIGF、补体3(C3)和B因子水平,并采用ROC曲线评估各项血清指标预测PE的效能。结果发病组孕妇血清s Flt-1、sFlt-1/PIGF、C3和B因子水平均高于未发病组,PIGF水平低于未发病组,差异均有统计学意义(均P<0.01)。ROC曲线显示,sFlt-1、PIGF、sFlt-1/PIGF、C3和B因子预测PE的AUC分别为0.662、0.771、0.789、0.643和0.691,在对PE的预测中sFlt-1/PIGF效能最佳,其截断值为3.4,灵敏度和特异度分别为0.859、0.771。结论PE孕妇机体内sFlt-1、PIGF、sFlt-1/PIGF、C3和B预测PE因子存在异常,对PE的预测具有一定价值。

Mir-125b和PIGF在早期流产孕妇绒毛组织及血清中的表达及意义

目的:研究微小RNA-125b(mir-125b)与胎盘生长因子(PIGF)在早期流产女性绒毛组织中及血清中的表达及意义。方法:选择2017年7月至2019年10月本院收治的孕早期自然流产妇女105例为研究对象,另选择同期105例人工流产孕妇为对照组,采集受试者外周静脉血血清,分离所有患者流产组织中绒毛膜组织,采用实时定量PCR检测血清及绒毛膜组织mir-125b、PIGF mRNA表达水平,采用免疫印迹法(WB)检测绒毛组织中PIGF蛋白表达水平,采用酶联免疫吸附试验(ELISA)检测血清PIGF水平,采用Pearson法分析血清及绒毛膜组织中mir-125b、PIGF蛋白水平相关性。绘制受试者工作特性曲线(ROC)分析血清mir-125b、PIGF水平对孕早期自然流产患者的预测价值。结果:与对照组比较,自然流产组女性绒毛膜组织mir-125b水平显著升高、PIGF mRNA和蛋白水平显著降低,血清mir-125b水平显著升高、PIGF水平显著降低,差异均有统计学意义(P<0.05)。Pearson法分析结果显示,自然流产孕妇绒毛膜组织、血清mir-125b水平与PIGF蛋白水平均呈负相关性(r=-0.643,P<0.05)。血清mir-125b、PIGF水平预测孕早期自然流产发生的曲下面积(AUC)分别为0.896(95%CI:0.850-0.943)、0.884(95%CI:0.838-0.929),mir-125b≥1.630预测自然流产发生的灵敏度为95.30%,特异度为84.60%,PIGF≤42.553 pg/mL预测自然流产发生的灵敏度为90.60%,特异度为77.90%;二者联合检测预测孕早期自然流产发生的AUC为0.954,灵敏度为89.60%,特异度为92.30%。结论:早期自然流产孕妇绒毛膜组织中mir-125b水平上调,PIGF水平下调,且二者呈负相关,可能对自然流产发生有一定预测价值。

依诺肝素钠联合硫酸镁对早发型重度子痫前期患者PIGF、sFlt-1、vWF、p-选择素水平的影响

目的探讨依诺肝素钠联合硫酸镁对早发型重度子痫前期患者胎盘生长因子(PIGF)、可溶性血管内皮生长因子受体1(sFlt-1)、血管性血友病因子(vWF)、p-选择素水平的影响。方法选取2017年1月至2020年1月本院收治的早发型重度子痫前期患者72例,采用随机数字表法分为观察组和对照组,各36例。对照组采用硫酸镁联合硝苯地平治疗,观察组采用依诺肝素钠联合硫酸镁治疗。比较两组PIGF、sFlt-1、vWF、p-选择素水平及妊娠结局。结果观察组PIGF水平高于对照组,sFlt-1、vWF、p-选择素水平低于对照组,差异有统计学意义(P<0.05);观察组胎儿窘迫、早产、剖宫产发生率均低于对照组,但差异无统计学意义。结论早发型重度子痫前期患者采用依诺肝素钠联合硫酸镁治疗,能有效改善PIGF、sFlt-1、vWF、p-选择素水平,改善妊娠结局。

Kyn/Trp、PIGF、sFlt-1及ACR值与妊娠期高血压疾病的关系

目的探讨妊娠期高血压疾病患者血清犬尿氨酸(Kyn)/色氨酸(Trp)、可溶性血管内皮生长因子受体-1(sFlt-1)、胎盘生长因子(PIGF)、随机尿白蛋白/肌酐比值(ACR)的变化及其与疾病严重程度的关系。方法选取2015年1月至2017年5月在丽水市人民医院就诊的妊娠期高血压疾病患者144例(病例组),选取同期正常妊娠妇女60例(对照组),检测两组的Kyn/Trp、PIGF、ACR和sFlt-1的水平,并根据患者的病情进行比较分析。结果病例组的ACR、sFlt-1值显著高于对照组(t值分别为21.668、5.193,均P<0.05);病例组的Kyn/Trp、PIGF值显著低于对照组(t值分别为6.819、9.878,均P<0.05)。病例组妊娠期高血压疾病、子痫前期轻度、子痫前期重度患者的ACR、sFlt-1值组间逐渐升高(F值分别为32.648、28.554,均P<0.05);妊娠期高血压疾病、子痫前期轻度、子痫前期重度患者的Kyn/Trp、PIGF值组间逐渐降低(F值分别为18.094、24.187,均P<0.05)。妊娠期高血压疾病患者24h尿蛋白值与ACR、sFlt-1值呈显著正相关(r值分别为0.671、0.624,均P<0.05),与Kyn/Trp、PIGF值呈显著负相关(r值分别为-0.668、-0.521,均P<0.05)。结论妊娠期高血压疾病患者的Kyn/Trp、PIGF水平较正常妊娠妇女降低,ACR、sFlt-1较正常妊娠妇女升高,并且与妊娠期高血压疾病患者病情程度具有一定的相关性。

血清HMGB1、sCD40L、PIGF、sFlt-1预测子痫前期价值

目的:探讨血清高迁移率族蛋白(HMGB1)、可溶性CD40L(sCD40L)、胎盘生长因子(PIGF)、可溶性血管生长因子受体-1(sFlt-1)预测子痫前期(PE)价值。方法:选择2019年1月-2020年12月本院产科收治的PE患者92例(PE组),分为轻度PE组(50例)和重度PE组(42例),同期产前检查正常孕妇50例为对照组,采用酶联免疫法检测各组血清HMGB1、sCD40L、PIGF、sFlt-1,采用受试者特异性曲线(ROC)分析血清各指标诊断及预测PE价值。结果:与对照组相比,PE组24 h尿蛋白、收缩压(SBP)、舒张压(DBP)、平均动脉压(MAP)、血清HMGB1、sCD40L、sFlt-1水平均较高,血清PIGF水平较低,且重度PE组各指标变化幅度高于轻度PE组(均P<0.05)。经Pearson相关因素分析,PE组SBP、DBP、MAP、24 h尿蛋白与血清HMGB1、sCD40L、sFlt-1呈正相关,与PIGF呈负相关(均P<0.05)。经ROC曲线分析,血清HMGB1、sCD40L、PIGF、sFlt-1联合诊断PE可获得最佳曲线下面积(0.810),敏感度、特异度分别为81.0%、82.1%。结论:血清HMGB1、sCD40L、PIGF、sFlt-1与PE发生及其血压升高有密切关系,联合检测可预测PE患者病情发生及转归情况,为PE临床诊断提供参考依据。

PIGF在湿性黄斑变性中的作用探讨

脉络膜新生血管是湿性黄斑变性(neovascularage-related macular degeneration,n AMD)的主要发病机制,而血管内皮生长因子(vascular endothelial growth factor,VEGF)促进新生血管的作用已受到广泛认可,目前针对VEGF不同靶点的药物已广泛运用于治疗n AMD。胎盘生长因子(placental growth factor,PIGF)是抗VEGF的一个新靶点,与VEGF-A有协同作用,可促进新生血管,刺激内皮细胞迁移增殖,介导免疫炎症反应,且在已成熟血管上无表达,特异性较高。本文就PIGF在n AMD中的作用进行探讨。