新生儿血清皮质醇、前列腺素合成酶、前列腺素表达水平与早产的关系及其意义

发布时间：2018-09-08 09:47

【摘要】：目的：近年来，早产儿出生率仍然在不断的升高。随着新生儿重症监护病房(NICU)的发展，早产儿的存活率有了明显提高。但早产儿各器官发育尚不成熟，其并发症及后遗症的发生严重影响早产儿远期生活质量。有效地防治早产是降低早产发生率、改善预后的关键。因此如何预防早产的发生已成为亟待解决的问题。首先必需明确早产的原因。目前已知的早产原因包括：感染、母亲年龄、子宫因素、孕期合并症及并发症、社会生活环境、经济状态等。其次，明确相应疾病状态下导致的早产分娩发动机制。虽然目前公认前列腺素是导致分娩发动的最后的共同通路[1]，但是具体调节机制至今仍未完全清楚。而且研究认为分娩发动是一个复杂的综合作用的结果，必须综合各种因素考虑[2]。近些年以来，Challis.et al等学者通过对绵羊以及哺乳动物模型的研究发现，胎儿的下丘脑-垂体-肾上腺轴（hypothalamic-pituitary-adrenal，HPA轴）的激活是分娩发动的中心机制[3]。HPA轴激活的直接结果是胎儿体内皮质醇增多。皮质醇可以直接影响胎盘前列腺素合成酶的表达，导致前列腺素的合成增多[3]。前列腺素作用于宫颈，使宫颈软化；作用于子宫平滑肌，使子宫收缩，最终促使分娩发动。由此推测皮质醇作为前列腺素合成酶的诱导因子，间接地促进前列腺素的合成而启动分娩。胎儿体内皮质醇的合成受多种因素的影响，不同病因状态胎儿体内皮质醇表达水平亦不同。尤其在胎儿应激状态下，皮质醇作为应激激素将会大量分泌。而皮质醇作为诱导因子，由其所形成的皮质醇-前列腺素合成酶-前列腺素的级联反应，在妊娠分娩中起重要作用。因此通过测定新生儿血中皮质醇及其相关因子水平，可以了解胎儿内分泌活动在妊娠分娩中的作用，为有效地预防早产的发生提供新思路。另外，虽然有效地预防是降低早产发生率的根本，然而合理的评价及干预是改善其远期预后的重要手段。有学者曾提出产前及产后皮质醇的水平影响新生儿大脑关键区域神经纤维的表达。这些区域包括海马以及与记忆相关的区域[4]。此外，前列腺素有维持胎儿动脉导管不闭的作用，从血流动力学上保证了胎儿重要器官得到含氧丰富的血供[5]。前列腺素还可调节胎儿下丘脑-垂体-肾上腺轴（HPA）的功能[6、7]，促进胎儿发育成熟。因此通过检测新生儿皮质醇、前列腺素水平，还可以指导新生儿疾病的防治，为改善其远期预后提供理论依据。方法：选择邢台市人民医院新生儿科收治的新生儿55例，首先根据胎龄分为足月新生儿对照组；早产儿组。其中足月新生儿对照组15例，其胎龄平均为37.6±0.50周、体重平均为3000g±430.43g、男8例，女7例；其次早产儿组根据分娩原因分为：特发性早产组、妊高症分娩组。其中特发性早产组20例，其胎龄平均为33.58±1.28周，体重平均为1990.59±408.68g，男13例，女7例；妊高症分娩组20例，其胎龄平均为33.83±3.10周，体重平均为1794.41±414.80g，男12例，女8例。各组内新生儿胎龄、出生体重、性别均无统计学差异，P0.05。所选新生儿母亲均为适龄产妇、无不良生活习惯、未使用抗生素、产前无感染病史、无胎膜早破、产前未使用促肺成熟药物；新生儿无宫内窘迫、窒息史、Apgar评分正常。 55例新生儿均在出生30min内采集外周静脉血并离心留取上清液，采用酶联免疫吸附法检测新生儿血清中皮质醇、前列腺素合成酶、前列腺素三者的含量。结合相关临床资料对比分析，并进行统计学处理。结果： 13组新生儿血清皮质醇水平变化（Fig1，Table1）足月新生儿对照组血清皮质醇水平高于特发性早产组，差异有统计学意义（P0.05）；足月新生儿对照组及特发性早产组血清皮质醇水平显著低于妊高症早产组，差异有统计学意义（P0.05）。 23组新生儿血清前列腺素合成酶水平变化（Fig2，Table2）足月新生儿对照组血清前列腺素合成酶水平高于特发性早产组，差异有统计学意义（P0.05）；足月新生儿对照组及特发性早产组血清前列腺素合成酶水平显著低于妊高症早产组，差异有统计学意义（P0.05）。 33组新生儿血清前列腺素的水平变化（Fig3，Table3）足月新生儿对照组血清前列腺素水平高于特发性早产组，差异有统计学意义（P0.05）；足月新生儿对照组及特发性早产组血清前列腺素水平显著低于妊高症早产组，差异有统计学意义（P0.05）。 4相关性分析 4.1新生儿血清皮质醇、前列腺素合成酶相关性分析（见Fig4、7、10,Table4）足月新生儿对照组血清皮质醇、前列腺素合成酶呈正相关，差异有统计学意义（r=0.895，P0.01）；特发性早产组新生儿血清皮质醇、前列腺素合成酶无相关性，差异无统计学意义（r=-0.349，P0.05）；妊高症早产组新生儿血清皮质醇、前列腺素合成酶呈正相关，差异有统计学意义（r=0.876，P0.01）。 4.2新生儿血清前列腺素合成酶、前列腺素相关性分析（见Fig5、8、11,Table5）足月新生儿对照组血清前列腺素合成酶、前列腺素呈正相关，差异有统计学意义（r=0.818，P0.01）；特发性早产组新生儿血清前列腺素合成酶、前列腺素无相关性，差异无统计学意义（r=-0.354，P0.05）；妊高症早产组新生儿血清前列腺素合成酶、前列腺素呈正相关，差异有统计学意义（r=0.770，P0.01）。 4.3新生儿血清皮质醇、前列腺素相关性分析（见Fig6、9、12, Table6）足月新生儿对照组血清皮质醇、前列腺素呈正相关，差异有统计学意义（r=0.761，P0.01）；特发性早产组血清皮质醇、前列腺素无相关性，差异无统计学意义（r=-0.139，P0.05）；妊高症早产组新生儿血清皮质醇、前列腺素呈正相关，差异有统计学意义（r=0.863，P0.01）。结论： 1足月新生儿对照组与特发性早产组相比，新生儿血清皮质醇水平足月新生儿对照组高于特发性早产组（P0.05），提示随着孕周的增加胎儿分泌皮质醇的能力增强。表明其水平变化反应胎儿肾上腺功能。 2足月新生儿对照组与妊高症早产组相比，新生儿血清皮质醇水平足月新生儿对照组小于妊高症早产组（P0.05），提示早产儿肾上腺具有良好的调节功能。妊高症时胎儿处于应激状态，皮质醇大量分泌。 3足月新生儿对照组血清皮质醇、前列腺素合成酶、前列腺素三者水平呈正相关关系。表明在正常妊娠过程中，胎儿内分泌活动参与妊娠分娩的过程。随着孕周的增加，胎儿肾上腺分泌的皮质醇逐渐增高。当皮质醇增高到一定程度时，其作为前列腺素的上游因子，，通过诱导前列腺素合成酶的表达，促进前列腺素的合成，从而启动分娩。三者之间的相互作用在维持妊娠及分娩发动中起重要作用。 4妊高症早产组新生儿血清皮质醇、前列腺素合成酶、前列腺素三者水平均同时升高，呈正相关性。表明胎儿在应激状态下，分泌较多皮质醇，并通过上述级联反应，使分娩提前启动，导致早产。 5特发性早产组新生儿血清皮质醇与足月新生儿对照组相比，其水平并未升高；在特发性早产组皮质醇、前列腺素合成酶、前列腺素三者之间无相关性。故推测皮质醇及其相关因子所形成的级联反应并未参与特发性早产的分娩发动。 6监测新生儿血清皮质醇水平，有利于评价新生儿肾上腺功能。 7深入研究皮质醇、前列腺素合成酶和前列腺素，应用分子生物学技术研究三者之间精密的调控机制，找到促发级联反应的扳机点，为妊高症早产的早期防治开拓新的途径。
[Abstract]:OBJECTIVE: In recent years, the birth rate of premature infants is still rising. With the development of neonatal intensive care unit (NICU), the survival rate of premature infants has been significantly improved. However, the organ development of premature infants is still immature. The complications and sequelae of premature infants seriously affect the long-term quality of life. So how to prevent the occurrence of preterm labor has become an urgent problem to be solved. First of all, it is necessary to clarify the causes of preterm labor. Although prostaglandins are currently recognized as the last common pathway leading to the onset of labor, the specific regulatory mechanism is still unclear. Moreover, studies have shown that the onset of labor is the result of a complex and comprehensive effect, and various factors must be taken into account. The activation of hypothalamic-pituitary-adrenal axis (HPA axis) is the central mechanism of labor initiation [3]. The direct result of HPA axis activation is the increase of fetal cortisol. Cortisol can directly affect the placental prostaglandin synthase surface. Prostaglandin acts on the cervix, softening the cervix; acts on the smooth muscle of the uterus, causing contraction of the uterus, and ultimately promoting the initiation of labor. The levels of cortisol expression in fetuses with different etiological factors are also different. Especially in fetal stress, cortisol, as a stress hormone, will be secreted in large quantities. As an inducer, cortisol, the cascade of cortisol-prostaglandin synthase-prostaglandin, plays an important role in pregnancy and childbirth. Therefore, by measuring the levels of cortisol and its related factors in the blood of newborns, we can understand the role of fetal endocrine activities in pregnancy and childbirth, and provide new ideas for effectively preventing the occurrence of premature delivery. Prenatal and postnatal cortisol levels have been suggested to affect the expression of nerve fibers in key brain regions of newborns. These regions include the hippocampus and memory-related areas [4]. Prostaglandin can also regulate the function of fetal hypothalamus-pituitary-adrenal axis (HPA) and promote fetal development and maturation.Therefore, the detection of neonatal cortisol and prostaglandin levels can also guide the prevention and treatment of neonatal diseases and provide theoretical basis for improving long-term prognosis.
Methods: Fifty-five neonates were selected from the Department of Neonatology, Xingtai People's Hospital, and divided into two groups according to gestational age: full-term neonate control group and preterm neonate group. Idiopathic premature delivery group, pregnancy-induced hypertension delivery group, including 20 cases of idiopathic premature delivery group, the average gestational age was 33.58 + 1.28 weeks, the average weight was 1990.59 + 408.68 g, 13 males, 7 females; pregnancy-induced hypertension delivery group, 20 cases, the average gestational age was 33.83 + 3.10 weeks, the average weight was 1794.41 + 414.80 g, 12 males, 8 females. There was no significant difference between the two groups, P 0.05. The mothers of the newborns were all puerperas of the right age, without unhealthy living habits, antibiotics, prenatal infection, premature rupture of membranes, and pulmonary maturation drugs. The newborns had no history of intrauterine distress, asphyxia and normal Apgar score.
The serum cortisol, prostaglandin synthase and prostaglandin were detected by enzyme-linked immunosorbent assay (ELISA). The clinical data were compared and analyzed.
Result:
Changes of serum cortisol levels in 13 groups of neonates (Fig1, Table1)
The level of serum cortisol in full-term neonate control group was higher than that in idiopathic preterm delivery group (P 0.05). The level of serum cortisol in full-term neonate control group and idiopathic preterm delivery group was significantly lower than that in PIH preterm delivery group (P 0.05).
Changes of serum prostaglandin synthetase levels in 23 groups of neonates (Fig2, Table2)
The level of serum prostaglandin synthase in term neonate control group was higher than that in idiopathic preterm delivery group (P 0.05). The level of serum prostaglandin synthase in term neonate control group and idiopathic preterm delivery group was significantly lower than that in pregnancy induced hypertension preterm delivery group (P 0.05).
Changes of serum prostaglandin levels in 33 groups of neonates (Fig3, Table3)
The level of serum prostaglandin in term neonate control group was higher than that in idiopathic preterm delivery group, the difference was statistically significant (P 0.05); the level of serum prostaglandin in term neonate control group and idiopathic preterm delivery group was significantly lower than that in pregnancy induced hypertension preterm delivery group, the difference was statistically significant (P 0.05).
4 Correlation Analysis
Correlation analysis of serum cortisol and prostaglandin synthetase in 4.1 neonates (see Fig4,7,10, Table4)
Serum cortisol and prostaglandin synthase were positively correlated in term neonate control group (r = 0.895, P 0.01); serum cortisol and prostaglandin synthase were not correlated in idiopathic premature infant group (r = - 0.349, P 0.05); serum cortisol and prostaglandin synthase were not correlated in idiopathic premature infant group (r = - 0.349, P 0.05); serum cortisol and The enzyme was positively correlated, and the difference was statistically significant (r=0.876, P0.01).
4.2 neonatal serum prostaglandin synthase, prostaglandin correlation analysis (see Fig5,8,11, Table5)
Serum prostaglandin synthase and prostaglandin were positively correlated in term neonate control group (r = 0.818, P 0.01); serum prostaglandin synthase and prostaglandin were not correlated in idiopathic premature infant group (r = - 0.354, P 0.05); serum prostaglandin synthase was not correlated in pregnancy induced hypertension premature infant group (P 0.354, P 0.05). Prostaglandin was positively correlated, and the difference was statistically significant (r=0.770, P0.01).
Correlation analysis of serum cortisol and prostaglandin in 4.3 neonates (see Fig6,9,12, Table6)
Serum cortisol and prostaglandin were positively correlated in full-term neonate control group (r = 0.761, P 0.01); serum cortisol and prostaglandin were not correlated in idiopathic preterm delivery group, and there was no significant difference (r = - 0.139, P 0.05); serum cortisol and prostaglandin were positively correlated in preterm pregnancy induced hypertension group, and the difference was statistically significant. Meaning (r=0.863, P0.01).
Conclusion:
1. Compared with the idiopathic preterm birth group, the serum cortisol level of the full-term neonate control group was higher than that of the idiopathic preterm birth group (P 0.05), suggesting that the ability of the fetus to secrete cortisol increased with the increase of gestational age.
Compared with the preterm group of PIH, the serum cortisol level of full-term neonates in the control group was lower than that in the preterm group of PIH (P 0.05), suggesting that the adrenal gland of preterm infants has a good regulatory function.
There was a positive correlation between the levels of serum cortisol, prostaglandin synthase and prostaglandin in the control group of full-term neonates, indicating that fetal endocrine activity was involved in the process of pregnancy and childbirth during normal pregnancy. As the upstream factor of prostaglandin, the synthesis of prostaglandin is promoted by inducing the expression of prostaglandin synthetase, thus initiating labor.
4. The levels of serum cortisol, prostaglandin synthase and prostaglandin in preterm infants with PIH were all increased at the same time, showing a positive correlation.
5. The serum cortisol level of neonates in idiopathic preterm delivery group was not higher than that of full-term neonate control group, and there was no correlation among cortisol, prostaglandin synthase and prostaglandin in idiopathic preterm delivery group.
6 monitoring the serum cortisol level of newborns is beneficial to evaluate adrenal function in neonates.
7. Deeply study cortisol, prostaglandin synthase and prostaglandin, study the precise regulation mechanism among them by molecular biology technology, find the trigger point of cascade reaction, and open up a new way for early prevention and treatment of pregnancy induced hypertension.
【学位授予单位】：河北医科大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R722.1

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