前白蛋白在孕妇血清及胎盘组织的表达与妊娠期高血压疾病严重程度的关系

Expression of prealbumin in maternal serum and placenta tissue of pregnant women and its relation with severity of hypertensive disorder complicating pregnancy

目的探讨在妊娠期高血压疾病、子痫前期(PE)、PE合并胎儿宫内生长受限(FGR)的孕妇血清及胎盘组织中,前白蛋白(PBA)表达及其临床意义。方法选择2014年1月至2016年1月,在首都医科大学附属北京潞河医院进行常规产前检查,并采取剖宫产术分娩的98例罹患不同程度妊娠期高血压疾病的单胎妊娠孕妇为研究对象。其中,被诊断为妊娠期高血压疾病者为31例、单纯PE者为33例、PE合并FGR者为34例,将其分别纳入妊娠期高血压疾病组、单纯PE组、PE合并FGR组。单纯PE组与PE合并FGR组的67例孕妇中,早发型PE为30例,晚发型PE为37例。选择同期于收集上述病例的同一家医院进行常规产前检查,并采取剖宫产术分娩的36例正常足月单胎妊娠孕妇作为研究对照,纳入对照组。分别采用酶联免疫吸附试验法与免疫组化法,对分娩前4组孕妇的血清及胎盘组织PBA表达进行检测。4组孕妇血清PBA比较,采用单因素方差分析,进一步两两比较,采用最小显著性差异(LSD)法。4组孕妇胎盘组织PBA表达呈阴性、弱阳性、中度阳性、较强阳性、强阳性率比较,采用Kruskal-WallisH秩和检验,进一步两两比较,采用Mann-WhitneyU检验,并采用Bonferroni法调整检验水准(α′=0.05/6=0.008)。本研究遵循的程序符合首都医科大学附属北京潞河医院人体试验委员会制定的标准,经过该伦理委员会批准(批准文号:2018LH-KS-025),并与所有受试者签署临床研究知情同意书。结果①4组孕妇年龄、孕次、产次、孕前人体质量指数(BMI)等一般临床资料比较,差异均无统计学意义(P>0.05)。②4组孕妇平均动脉压、24h尿蛋白定量、分娩孕龄、新生儿出生体重、血清PBA比较,差异均有统计学意义(F=233.773、222.081、113.597、214.420、90.147,P<0.001)。对4组孕妇血清PBA进一步进行两两比较的结果显示,妊娠期高血压疾病组、单纯PE组、PE合并FGR组孕妇血清PBA,均显著低于对照组,单纯PE组、PE合并FGR组孕妇血清PBA,均显著低于妊娠期高血压疾病组,PE合并FGR组孕妇血清PBA,显著低于单纯PE组,并且差异均有统计学意义(P<0.05)。③PBA表达于胎盘绒毛滋养细胞细胞质,为粗大棕褐色颗粒。对照组孕妇胎盘组织中,PBA呈较强阳性和(或)强阳性表达;单纯PE组及PE合并FGR组孕妇胎盘组织中,PBA呈阴性或弱阳性表达;妊娠期高血压疾病组,则呈中度阳性表达。④4组孕妇胎盘组织PBA表达呈阴性、弱阳性、中度阳性、较强阳性、强阳性率总体比较,差异有统计学意义(χ2=39.405,P=0.013)。进一步进行两两比较的结果显示,与对照组相比,单纯PE组、PE合并FGR组孕妇胎盘组织PBA减低,并且差有统计学意义(Z=3.416、4.846,P<0.001);与妊娠期高血压疾病组相比,PE合并FGR组孕妇胎盘组织PBA减低,并且差异有统计学意义(Z=2.829,P=0.004)。⑤早发型PE孕妇血清及胎盘组织PBA,均较晚发型PE低,并且差异均有统计学意义(t=3.160、P=0.002,χ2=8.201、P<0.001)。结论PBA在妊娠期高血压疾病、PE、PE合并FGR孕妇血清及胎盘组织中,均呈低表达,在早发型PE孕妇中尤其明显,并且PBA随着妊娠期高血压疾病严重程度增加,而降低。

Objective To investigate the expressions of prealbumin (PBA) in maternal serum and placenta tissue of pregnant women with hypertensive disorder complicating pregnancy, preeclampsia (PE) and PE with fetal growth restriction (FGR) and its clinical significance. Methods A total of 98 cases of singleton pregnancy women with different degrees of hypertensive disorder complicating pregnancy who had routine prenatal examination and delivered by cesarean section in Beijing Luhe Hospital, Capital Medical University from January 2014 to January 2016 were selected as research subjects. Among them, 31 pregnant women with hypertensive disorder complicating pregnancy, 33 cases with PE, and 34 cases with PE and FGR were divided into hypertensive disorder complicating pregnancy group, simple PE group and PE with FGR group, respectively. There were 30 cases of early-onset PE and 37 cases of late-onset PE among 67 pregnant women in simple PE group and PE with FGR group. Another 36 cases of normal full-term singleton pregnancy women who had routine prenatal examination and delivered by cesarean section in the same hospital during the same period were included into control group. Enzyme linked immunosorbent assay and immunohistochemical method were applied to detect the serum PBA levels and the expressions of PBA in placenta tissues of pregnant women before delivery. The serum PBA levels of 4 groups were compared by one-way ANOVA method, and further pairwise comparison was conducted by least-significant difference (LSD) method. Rates of negative, weakly positive, moderately positive, less strongly positive and strongly positive PBA expressions in placenta tissues of pregnant women in 4 groups were compared by Kruskal-Wallis H rank sum test, and Mann-Whitney U test was used for further pairwise comparison by adjusting size of test with Bonferroni method (α′=0.05/6=0.008). The procedures followed in this study were in accordance with the standards established by the Committee of Investigation in Human Beings Beijing Luhe Hospital, Capital Medical University, and this study was approved by the committee (Approval No. 2018LH-KS-025). All the subjects signed the informed consents for clinical trials. Results ①There were no statistical differences among 4 groups in the general clinical data, such as age, gravidity, parity, and body mass index (BMI) before pregnancy and so on ( P >0.05).② There were statistical differences among 4 groups in the mean arterial pressure, 24 h urine protein quantitation, gestational age, neonatal birth weight and serum PBA level ( F =233.773, 222.081, 113.597, 214.420, 90.147;P <0.001). The results of further pairwise comparison of serum PBA levels among 4 groups showed that the serum PBA levels in hypertensive disorder complicating pregnancy group, simple PE group and PE with FGR group were significantly lower than that in the control group, serum PBA levels in simple PE group and PE with FGR group were significantly lower than that in hypertensive disorder complicating pregnancy group, serum PBA level in PE with FGR group was significantly lower than that in simple PE group, and all the differences were statistically significant ( P <0.05).③PBA was expressed in cytoplasm of placental villus trophoblast cells and represented as coarse brown particles. In maternal placental tissues of pregnant women in control group, PBA was less strongly positively and/ or strongly positively expressed in maternal placental tissues of pregnant women in simple PE group and PE with FGR group, PBA was negatively or weakly positively expressed;and PBA was moderately positively expressed in maternal placental tissues of pregnant women in hypertensive disorder complicating pregnancy group.④There were statistical differences among 4 groups in the rates of negative, weakly positive, moderately positive, less strongly positive and strongly positive expression of PBA in maternal placental tissues (χ 2 =39.405, P =0.013). The results of further pairwise comparison showed that PBA expression in maternal placental tissues of pregnant women in simple PE group and PE with FGR group both were lower than that in the control group, and both the differences were statistically significant ( Z =3.416, 4.846;P <0.001). Compared with hypertensive disorder complicating pregnancy group, PBA expression in maternal placental tissues of pregnant women in PE with FGR group decreased, and the difference was statistically significant ( Z =2.829, P = 0.004).⑤Serum PBA level and PBA expression in maternal placental tissues of pregnant women with early-onset PE were lower than those with late-onset PE, and the differences were statistically significant ( t = 3.160, P =0.002;χ 2 =8.201, P <0.001). Conclusions PBA is lowly expressed in serum and placental tissues of pregnant women with hypertensive disorder complicating pregnancy, PE, and PE combined with FGR, especially in pregnant women with early-onset PE. And the expression level of PBA decreases as the severity of hypertensive disorder complicating pregnancy increases.