| Hypertensive disorder complicating pregnancy (HDCP) is a common obstetric disease,and many researches have confirmed that systemic small vessel spasm is the basic pathological changes of hypertensive disorder complicating pregnancyfor many years.Hypertensive disorder complicating pregnancy seriously affected the health of mother and infant.It is one of the common causes of adverse pregnancy outcomes.The incidence rate of HDCP of6.4%-7.0%reported abroad, and the average incidence of HDCP was9.4%in our country.Preeclampsia is a severe stages of hypertensive disorder complicating pregnancy,the main clinical manifestations is hypertension, proteinuria, edema, and multi-organ systemic damage after20weeks of pregnancy pregnant.It may occured convulsion, heart failure, placental abruption and disseminated intravascular coagulation and other complications in severe patients, and it can raise the risk of cardiovascular disease in those women after the postpartum. The effects on the fetus are that this disease can cause placental function decline, fetal growth restriction, fetal distress and iatrogenic premature delivery and so on. Preeclampsia is a major cause of mortality of maternal and perinatal, especially in the developing countries, the incidence of Preeclampsia is about2%-8%[2],and it has a trend of gradually increasing in recent years.The risk of preeclampsia for mothers and infants has already been fully affirmed, but if the pregnant women with preeclampsia, especially with the early onset severe preeclampsia, there is no effective clinical treatment in addition to terminate the pregnancy.Earlier already researcheshave reported that if the high-risk pregnant women used a small prophylactic dose of aspirin before16weeks of gestation, the incidence of the pregnant women with subsequent preeclampsia and intrauterine growth restriction will decreased by about5O%.The scholars and experts of our country orabroad have devoted to the exploration of the etiology and pathogenesis of preeclampsia for many years, but so far the etiology and pathogenesis of preeclampsia is still not very clear.In rencent years, a lot of scholars of our country orabroad are engaged in the study of early prediction of preeclampsia. Expected that it may also helpful to discover the clues to the etiology and pathogenesis. It appears a series of early biomarkers associated with preeclampsia,but so far, there is no preeclampsia screening marker or method is economic, effective and dependablewhich can be widely applied to clinical.Therefore, the exploration of higher sensitvity and specificity biomarkers and screening methods associated with preeclampsia which can be widely applied in clinical may very helpful for early screening of high-risk population of preeclampsia. Given reasonable treatment before the clinical symptoms occurs, it would effectively reduce the morbidity and mortality of pregnant women and perinatal infant, and it may also very useful to discover the clues to the etiology and pathogenesis of preeclampsia. The early realization of early prediction, prevention, diagnosis and treatment with preeclampsia has also been the focus and hotspot of pathological obstetrics.The theory has been generally accepted that shallow placental implantation, immune maladaptation, oxidative stress, vascular endothelial injury and genetic susceptibility are the main cause of preeclampsia etiology. The recognized process of preeclampsia can be divided into two stages. The first phase began with the placenta of defect formation:abnormal formation was caused by uneven placental perfusion, hypoxia, oxidative stress of the placenta and so on, thisrisk factors mayalso can aggravatethedamage of placental function; The second stage is the clinical symptoms: the consequence of damaged vascular endothelial and the relevant organs of the body of pregnant woman with preeclampsia would cause the clinical symptoms which are hypertension, protein urine and edema. In recent years, many researches indicated that the damaged vascular endothelial is the key to the pathological changes of preeclampsia [4], and oxidative stress is an important link of the first phase and the second phase of preeclampsia[5]. However, the pathogenesis of those two stages is still not very clear.Many domestic and foreign scholars have done a lot of researchesin order to realize the early prediction, prevention, diagnosis and treatment of preeclampsia. More and more evidences indicated that the imbalance of angiogenesis factors in maternal blood circulation (such as placenta growth factor) and anti-angiogenesis factors (such as soluble vascular endothelial growth factor receptor-1) was very relate to the pathogenesis of preeclampsia[6]. With the development of gene expression microarray technology, some scholars discover that the oxidative stress which induced by free hemoglobin is closely related to the development of preeclampsia.At present,the relationship between placental growth factor and soluble vascular endothelial growth factor receptor-1and the pathogenesis of preeclampsia has become the hotspot of research. But the correlation study and report on fetal hemoglobin, a1-macroglobulin and preeclampsia is rare.Objective:To investigate the expression differences of fetalhemoglobin(HbF),al-microglobulin(al-MG),soluble vascular endothelial growth factor receptor-1(sFlt-1) and placental growth factor(PlGF) in maternal serum of normal pregnancy groupand preeclampsiagroup,and also the expression differences of al-microglobulin in maternal urine between those two groups. To discuss the effects of this biomarks of fetal hemoglobin,al-microglobulin, sFlt-1and PlGF in the pathogenesis of preeclampsia. To evaluate the diagnostic value with these indicators alone or together through using logistic regression and Receiver Operating Characteristic.To provide a reliable theoretical basis of early predict, prevent and treatment of preeclampsia.Materials and methods:1. Material source:Select50pregnant woman with preeclampsia (mild=20, severe=30) from Shenzhen Maternity and Child Healthcare Hospital, From2012April to October. The age ranged from21to35years old, the average age was (29.45±4.5) and (28.7±3.7) years old, the average gestational weeks were (38.76±1.24) and (38.41±0.98) weeks. There are23normal pregnant women without complications as control group. The age ranged from22to43years old, mean age (29.1±4.4) years old, the average gestational age (39±0.73) weeks, the difference of mean age, mean gestational age and parity were compared between the three pregnant groups which is no significant difference(p>0.05). The selected cases were singleton pregnancy, except for heart disease, diabetes, chronic hypertension, renal disease, connective tissue disease, infection, hyperthyroidism during pregnancy history, and no special drug history. Immediate extraction of elbow venous blood5ml into anticoagulation glass tube before the person accept the treatment, static30min,let it to self-curing, then2000g/min centrifuge10min, separate the serum in-80℃refrigerator and tested.10ml Urine was collected in sterile centrifugal tube of15ml,then to centrifuge2000g/min forlOmin, sent the supernatant was separated into-80℃refrigerator and tested.2.Methods:Thawing at room temperature, then centrifuged at3000rpm for2minutes in4℃high-speed refrigerated centrifuge, the supernatant was used for experimental analysis. Using enzyme-linked immune sorbent assay (ELISA) to detect the peripheral serum fetal hemoglobin, al-microglobulin, soluble vascular endothelial growth factor receptor-1,placental growth factor and urinary α1-microglobulin concentration in normal pregnancy group and preeclampsia group. Get the OD value of the samples from the Enzyme mark instrument.3. Statistical method:Using excel software and SPSS13.0statistical software for data processing. Using the mean±standard deviation(x±s) to express the measurement data, Using two independent samples t test to compare the two samples, using single factor analysis of variance (One-way ANOVA) to many groups compares.using Logistic regression and ROC curve characteristics to evaluate the value of diagnosis preeclampsia for index alone or in combination. The inspection level is0.05,theistically significant differences in P<0.05.Result:1.1The levels of Serum fetal hemoglobin in normal group(n=23) and preeclampsia group(n=50) are(74.83±23.57)μg/ml,(108.78±36.77)μg/ml, the differences between the two groups was statistically significant (P<0.05).1.2Levels of Serum fetal hemoglobin in normal group, mild group and severe preeclampsia group are:(74.83±23.57)μg/ml,(99.05±31.13)μg/ml,(115.27±39.24)μg/ml, the integral comparison of differences between three groups was statistically significant (P<0.05).2.1The levels of Serum α1-microglobulin in normal group(n=23) and preeclampsia group(n=50) are (1.73±0.50)μg/ml,(2.49±0.85)μg/ml, the differences between the two groups was statistically significant (P<0.05).2.2The levels of serum α1-macroglobulin of normal group, mild group and severe group of preeclampsia were:(1.73±0.50)μg/ml,(2.27±0.80)μg/ml,(2.64±0.86)μg/ml, the differences between three groups was statistically significant (P<0.05). 3.1The levels of Serum sFlt-1in normal group(n=23) and preeclampsia group(n=50) are(2453.62±742.33)ng/l,(3589.89±2139.31)ng/l,the differences between the two groups was statistically significant (P<0.05).3.2The levels of serum sFlt-1of the normal group, mild preeclampsia group and severe group are (2453.62±742.33) ng/L,(3122.68±1526.41)ng/L,(3901.36±2440.40) ng/L, the difference between the three groups (P<0.05) is statistical significance (P<0.05).4.1The levels of serum PIGF of normal group(n=23) and preeclampsia group(n=50) are (150.50±63.72)ng/l,(103.48±56.03) ng/1, the difference between the three groups (P<0.05) is statistical significance (P<0.05).4.2The serum PIGF levels of normal group, mild preeclampsia group and severe group were:(150.50±63.72) ng/L,(118.42±74.14) ng/L,(93.52±38.04) ng/L, difference was statistically significant between the overall comparison group (P<0.05).5.1The levels of serum sFlt-1/PIGF ratio of normal group(n=23) and preeclampsia group(n=50) are (17.80±6.19),(44.44±31.76).the difference between the three groups (P<0.05) is statistical significance (P<0.05).5.2The serum sFlt-1/PlGF ratio of normal group, mild preeclampsia group and severe group were:17.80±6.19,36.61±27.58,49.66±33.71,the difference is statistically significant between the overall comparison group (P<0.05).6.1The levels of urine alpha1-microglobulin of normal group(n=23) and preeclampsia group(n=50) are (1.00±0.64)μg/ml,(1.63±1.25)μg/ml.the difference between the three groups (P<0.05) is statistical significance (P<0.05).6.2The urine alpha1-microglobulin levels of normal group, mild preeclampsia group and severe group were(1±0.64)μg/ml,(1.48±1.20)μg/ml,(1.72±1.29)μ g/ml, was difference between the overall comparison group is statistically significant (P<0.05)7.The research object of serum α1-microglobulin level and urine alpha1-microglobulin levels were (2.25±0.83)μ g/ml,(1.53±1.91)μg/ml, the difference between the two groups was statistically significant (P<0.05).8.ROC curve (AUC) of fetal hemoglobin, serum1-α protein, sFlt-1, PlGF microspheres, the ratio of sFlt-1/PlGF and urine alpha microglobulin were:0.794(95%CI,0.680±0.908, P0.05),0.805(95%CI,0.697±0.913, P<0.05),0.690(95%CI,0.562～0.817, P<0.05),0.754(95%CI,0.645～0.864,P<0.05),0.801(95%CI,0.703～0.899, P<0.05),0.648(95%CI,0.517～0.779. P<0.05).9. The Logistic regression analysis showed that the characteristics of the ROC curve of several indicators combined together:①Combining fetal hemoglobin and serum a1-macroglobulin using logistic regression analysis yieled an area under the curve of0.876(95%CI,0.791～0.960, P<0.05), and a sensitivity of82%at a specificity of78.3%.②Combining fetal hemoglobin, serum α1-microglobulin and urine alpha1-microglobulin using logistic regression analysis yieled an area under the curve of0.907(95%CI,0.837～0.977, P<0.05), and a sensitivity of76%at a specificity of95.7%.③Combining fetal hemoglobin,α1-microglobulin and sFlt-1using logistic regression analysis yieled an area under the curve of0.906(95%CI,0.834～0.978, P<0.05), and a sensitivity of78%at a specificity of95.7%.④Combining fetal hemoglobin,α1-microglobulin and PIGFusing logistic regression analysis yieled an area under the curve of0.924(95%CI,0.862～0.986, P<0.05), and a sensitivity of76%at a specificity of91.3%.⑤Combining fetal hemoglobin,α1-microglobulin and sFlt-1/PlGF using logistic regression analysis yieled an area under the curve of0.941(95%CI,0.888～0.994, P<0.05), and a sensitivity of82%at a specificity of95.7%.⑥Combining fetal hemoglobin,α1-macroglobulin, sFlt-1and urine alphal- microglobulin using logistic regression analysis yieled an area under the curve of0.915(95%CI,0.848±0.981, P<0.05), and a sensitivity of80%at a specificity of95.7%.⑦Combining fetal hemoglobin,al-microglobulin,PlGF and urine alpha1-microglobulin using logistic regression analysis yieled an area under the curve of0.933(95%CI,0.877～0.989, P<0.05), and a sensitivity of80%at a specificity of95.7%.⑧Combining fetal hemoglobin,al-microglobulin,sFlt-1/PlGF and urine alpha1-microglobulin using logistic regression analysis yieled an area under the curve of0.943(95%CI,0.891～0.996,P<0.05), and a sensitivity of90%at a specificity of91.3%.Conclusion1.Fetal hemoglobin, a1-microglobulin, sFlt-1, PlGF maybe involved in the pathogenesis of preeclampsia. but the level of them are all have nothing to do with the patient’s condition, therefore, this biological marks can’t be well used as to monitor the changes of the patient’s condition..2.0xidativestress induced by fetal hemoglobin maybe involved in the pathogenesis of preeclampsia during the bridge of the first stage to the second stage.3. The ratio of sFlt-1/PlGF in preeclampsia group is significant higher than the control groups, the imbalance of sFlt-1and PlGF may participate in the pathogenesis ofpreeclampsia.4. Combining the different biological indicators could increase the diagnostic value ofpreeclampsia.5. The diagnosis value of preeclampsia through serum a1-MG maybe more superior to urine a1-MG. But urine a1-MG can be used as an indexes to improve the accuracy of forecasting or screening and diagnose for PE. |
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