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早产儿血胃动素和胃泌素的相关研究
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摘要
目的:早产儿是一个特殊的群体,大多由于存在自身的发育不完善或各种合并症尤其是围生期的脑损伤而导致喂养不耐受,造成机体基础情况较差,因此,早产儿的喂养成为影响其生存和生活质量的一个重要问题。MTL和GAS均为重要的胃肠激素,不仅涉及胃肠功能调节,而且对于神经系统和其它系统的功能也有调节作用。新生儿缺氧缺血性脑损伤(hypoxic-ischemiC brain damage,HIBD)是指各种围生期窒息引起的部分或完全缺氧而导致的新生儿脑损伤,临床常见有新生儿窒息(asphyxia of newborn)、新生儿缺氧缺血性脑病(hypoxic-iSchemic encephalopathy,HIE)及新生儿颅内出血(neonatal intracranial hemorrhage,ICH),是引起新生儿急性死亡和儿童伤残的重要原因之一。新生儿缺氧缺血性脑损伤患儿常伴有胃滞留、呕吐、腹胀以及应激性溃疡等胃肠功能紊乱的表现。本研究旨在通过对早产儿血胃动素(motilin,MTL)和胃泌素(gastrin,GAS)水平的测定,探讨早产儿及合并缺氧缺血性脑损伤(HIBD)早产儿胃肠激素水平;小剂量红霉素对喂养不耐受早产儿干预治疗的效果及其临床意义。
     方法:以50例早产儿为观察组:其中包括合并HIBD的早产儿23例,此为合并HIBD早产儿组;排除HIBD的早产儿27例,为排除HIBD早产儿组,其中存在喂养不耐受者18例为喂养不耐受早产儿组,9例喂养耐受的早产儿为喂养耐受早产儿组。以20例正常足月新生儿为正常对照组。应用放射免疫分析法(radioimmunoasssay,RIA)测定观察组和对照组喂养前血浆胃动素(MTL)和血清胃泌素(GAS)的含量。观察组及对照组新生儿均于清晨空腹状态下抽取静脉血4ml,其中2ml,注入预冷的含30μl10%草酸钠(EDTA-2Na)和30μl抑肽酶的试管中,充分混匀后于4℃下离心20min,吸取血浆后置-20℃冰箱内保存待测MTL;未经抗凝的2ml血于4℃下离心20min取血清放置-20℃冰箱内保存待测GAS。采用解放军总医院东亚免疫技术研究所提供的~(125)I标记MTL放射免疫分析盒以及由北京福瑞生物工程公司提供的~(125)I标记GAS放射免疫分析盒,均严格按说明书操作;用北京医用离心机厂提供的LDR4-8 4℃低温离心机进行分离;测量仪器采用西安二六二厂生产的EJ-2003型全自动6-免疫计数器。对18例喂养不耐受早产儿中的12例予小剂量红霉素进行干预治疗。
     统计学处理:应用SAS6.0软件包,两样本均数间比较采用t-test程序进行t检验,全部数据以(?)±s表示,两样本间率的比较采用x~2的Fisher精确概率,P<0.05为差异有统计学意义。
     结果:①合并HIBD早产儿血MTL和GAS水平均较正常足月儿、排除HIBD的早产儿高(P<0.01);②排除HIBD的早产儿血中MTL和GAS水平均较正常足月儿低(P<0.05);其中喂养不耐受的早产儿血中MTL和GAS水平与喂养耐受早产儿比较均有显著性差异(P<0.05),喂养耐受的早产儿血中MTL和GAS水平与正常对照组比较均无显著性差异(P>0.05);③对喂养不耐受早产儿的红霉素干预治疗组与其对照组比较效果有显著性差异(P<0.05)。
     结论:早产儿存在MTL和GAS分泌异常,监测血MTL和GAS水平有助于及早发现患儿是否有发生喂养不耐受或HIBD的可能,小剂量红霉素对喂养不耐受的早产儿有较好的治疗效果。
Objective: Preterm infants are a special group. Most of these infants suffer from feeding intolerance because of maldevelopment or various kinds of complications especially perinatal brain damage. And their nutrition situation becomes worse. Therefore, the feeding of preterm infants comes to be an important matter which influences the living and the quality of life. Hypoxic-ischemic brain damage (HIBD), due to asphyxia in perinatal period, is a kind of neonatal brain damage caused by partly or completely hypoxia, including neonatal asphyxia, neonatal hypoxic-ischemic encephalopathy (HIE) and neonatal intracranial hemorrhage (ICH), which is one of the important reasons that lead to acute death of newborns and disability of children. Newborns with HIBD usually accompany manifestations of gastrointestinal dysfunction such as gastric retention, emesis, abdominal distention and stress ulcer and so on. Both Motlin (MTL) and gastrin (GAS) are the most important gastrointestinal hormones. They relate not only to all the accommodation of gastrointestinal function, but also to nervous system and many other systems. According to detecting the blood MTL and GAS levels, we are hoping to explore the clinical significance about the gastrointestinal hormone secretion in preterm infants and preterm infants with hypoxic-ischemic brain damage (HIBD) ; and to observe therapeutic effect of erythromycin in small dose on preterm infants with feeding intolerance.
     Materials and methods: Objective: The observed were 50 cases of preterm infants. This 50 cases of preterm infants included 23 cases of preterm infants with HIBD, 27 cases of preterm infants without HIBD (including 18 cases of infants with feeding intolerance). The normal control was 20 cases of normal newborns. Methods: The plasma motilin and serum gastrin levels in 50 cases of preterm infants and the 20 cases of normal newborns were measured by radioimmunoassay (RIA). 4 ml vein blood of all the objects was taken on in the morning before being fed, 2 ml was poured into a precooling tube which contained 30μl 10% EDTA-2Na and 30μl Aprotinin, then was centrifugalized for 20 min at 4℃after intensively mixed, we took the plasma and reserved it at -20℃for MTL' s measurement; the other 2 ml blood was centrifugalized for 20 min at 4℃,then we took the serum and reserved it at -20℃for GAS's measurement. We adopted the ~(125)I MTL radioimmunoassay boxes offered by the East Asia Immuno-technology Institute of PLA General Hospital and ~(125)I GAS radioimmunoassay boxes offered by Beijing Furi Bioengineering Company, and operated according to the directions strictly; adopted the LDR4-8 4℃refrigerated centrifuge offered by Beijing Clinical Centrifuge Factory to centrifugalize the blood; The measuring apparatus is the EJ-2003 automatic 6-immuno-counter produced by Xi'an 262 Factory. The intervention of erythromycin in small dose of 3~5mg/(kg·d) was carried out on 12 cases of infants with feeding intolerance.
     Statistical treatment: We use SAS 6.0 package to deal with all the data, and adopt t-test procedure to make comparison between twogroups. Data is expressed as mean±standard variance (x|-±s). We adopt the fisher test of x~2 test to make the ratio comparison between two groups. P<0. 05 means that the analysis has statistical significance.
     Results:①Compared to the normal control and the preterm infants without HIBD group, the blood MTL and GAS levels of preterm infants with HIBD were higher (P<0. 01 ) .②The blood MTL and GAS levels of preterm infants without HIBD were lower than the normal control (P<0.05). There was significant difference between the feeding intolerance and the feeding tolerance groups of preterm infants (P<0. 05), while there was no significant difference between the preterm infants without feeding intolerance and the normal control (P>0.05).③The effect of erythromycin therapy had significant difference between the interventional group and the control (P<0.05).
     Conclusion: The preterm infants have abnormal secretion of plasma motilin and serum gastrin. Detecting blood MTL and GAS levels is helpful to infer the possibility of feeding intolerance or the HIBD. There is good effect of erythromycin therapy to the preterm infants with feeding intolerance.
引文
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