【作者】 王旭；

【导师】 薛守祥；

【作者基本信息】 吉林大学 ， 儿科学， 2004， 硕士

【摘要】 新生儿缺氧缺血性脑病（HIE）是指围产期缺氧窒息，导致脑的缺氧缺血性损伤。HIE是围产期新生儿死亡的重要原因，并常导致严重的神经系统后遗症，使人口的整体素质下降。近年来，尽管国际国内学者进行了大量研究，并在HIE发病机制、诊断和治疗等方面取得了许多成果，但对其发病机制还不十分明确，许多问题还有争论，还没有可靠的治疗手段。因此，仍然是新生儿学科研究的热点问题。在对其发病机制的研究中多数研究认为，HIE是一个多因素介导和参与的过程，缺氧缺血后脑能量代谢衰竭、脑血管自动调节功能受损、兴奋性氨基酸大量释放、细胞内Ca2+超载以及大量氧自由基产生、一氧化氮（NO）、β-内啡肽、中性粒细胞及血小板活性因子等作用，致使神经元损伤、脑细胞刁亡等，脑功能不同程度损伤。并有很多研究认为某些细胞因子和生物酶的变化在HIE发病中有重要意义。 为探讨HIE中TNF-α、NSE的作用，本研究采用双抗体夹心法（ELISA），对50例不同程度的HIE患儿进行了血清TNF-α和NSE动态水平测定，并与20例正常新生儿出生第一天的TNF-α和NSE水平进行对照分析。TNF-α测定结果显示：轻度HIE患儿与正常对照组新生儿比较，生后1天血清TNF-α水平即升高，有显著差异（P<0.05），而后下降，第3天、7天与对照组相比，已无显著差异（P>.05）。中度组与对照组相比，第1、3天时TNF-α<WP=28>水平明显升高，一天时有极显著差异（P<0.01），三天时差异显著（P<0.05），而七天时与对照组相比，差异已无显著意义（P>.05）。重度组一天、三天、七天时与对照组相比均有极显著差异（P<0.01）轻、中、重各组中，一天与三天有显著差异（P<0.05）；三天与七天相比均无显著差异（P>.05）。由此说明，轻、中、重度HIE患儿，TNF-α水平在疾病早期均有升高，且一天与三天间有水平上的差异，程度越重，水平越高。但轻度患儿TNF-α水平很快下降，程度越重，TNF-α水平升高持续时间越长。由此说明，早期TNF-α水平的轻度升高，可能对患儿的脑损伤有保护做用。提示TNF-α水平高低可以有助于HIE早期诊断，同时可以协助HIE程度的判定。由此推测，其有成为HIE诊断依据客观指标的可能。推测适量降低TNF-α水平可有效减轻脑损伤。NSE测定结果显示：与正常对照组新生儿比较，轻度HIE患儿NSE水平无明显升高（P>0.05）；中度组在一天、三天时升高水平有极显著差异（P<0.01），且三天与一天相比，虽水平已有下降，但仍有极显著差异（P<0.01），至七天时与三天及对照组间均无显著差异（P>.05）；重度组虽第3、7天较第1天有下降，但一天、三天、七天与对照组相比均有极显著差异（P<0.01），而一天与三天、三天与七天相比，均无显著差异（P>.05）。提示中、重度HIE患儿于一天时NSE水平升高显著，三天时大部分患儿的NSE水平降低而重度者则持续高于对照组。若七天时基本恢复正常，则预后相对好，持续升高者预后不良，死亡者NSE则呈持续性增高<WP=29>（24h内、第3天、第7天结果分别为23.38、26.51、24.68μg/L）。总之，HIE新生儿血清NSE的测定对判断HIE的脑损伤程度及观察疗效和判断预后都具有重要的临床意义。 国内外有关NSE和TNF-α与新生儿缺氧缺血性脑病的关系的报导较多，多认为其水平与新生儿缺氧缺血脑病的严重程度有关，并且具有时间依赖性。本研究结论与之相符。在新生儿缺氧缺血脑病中，有关TNF-α与NSE相关性的研究，国内未见报道，本研究证实了早期中、重度HIE患儿TNF-α与NSE的变化成正相关（0<r<1），提示TNF-α对NSE的分泌可能具有一定的调解作用。本文还探讨了抗TNF-α中合治疗的可能性，试图为疾病的早期干预和指导治疗提供理论依据。更多还原

【Abstract】 Hypoxic ischemic (HIE) of newborn is the damage in brain because of perinatal hypoxia or asphyxiation. HIE is an important cause that made newborn dead in perinatl stage. It often make serious sequela of nervous system, and make the predisposition of the whole population descent. Recently years, although scholar of international and internal have proceed a lot of investigation, and have made a lot of achievement in pathogenesis, diagnosis and therapy in HIE, the pathogenesis of HIE is still not clear fully. There are many altercation in this problem, but it have not dependable therapeutic tool yet. So it is an hot spot in neonatology. Most study think that multiple factor has take part in the process in HIE. After ischemia and hypoxia, brain energy metabolism shutdown, cerebral vessels self-adjustment was damaged, excitatory amino acids (EAA) releas largely, Ca2+ in cell overloading and much oxygen-derived free radidicals releas ,action of nitrogen monoxide (NO), β- endorphin, neutrophil, blood platelet active factor and so on, all this may cause neur damage and brain cells dead and so on ,the faction of brain have been damaged in aniso-level. Many investigation show that the change of some cytokine and enzyme have important significance in episod of HIE. In order to evaluate the action of tumor nerosis factor-alpha (TNF-a) NSE and find the relationship between TNF-a、NSE and <WP=31>HIE, TNF-a, NSE were measured by enzyme-linked immunoadent assay (ELISA) method in 50 Neonates with hypoxic ischemic encephalpathy (HIE) on difference stage and difference degree and 20 healthy newborn who was born 1 day later as control. The result show that in light group serum TNF-a level increased significantly in patients with HIE at the first day after birth than those in control group (p<0.05), then the serum TNF-a level in patients with HIE at the third and seventh day after birth begin descent, and have no significance in contrast with those in control group (p>0.05). The serum TNF-a level in patients with HIE at the first day and the third day increase significantly in miderate .The serum TNF-a level in patients with miderate group of HIE at the first day after birth increased significantly than those in control group (p<0.01), The serum TNF-a level in patients with miderate group of HIE at the third day after birth increased significantly than those in control group (p<0.05); but at the seventh day after birth didn’t have significance with those in control group (P>0.05). The serum TNF-a level increased significantly in patients with the severe group of HIE at the first day, the third day and the seventh day after birth increased significantly than those in control group (p<0.01), among three groups of HIE, the serum TNF-a level in patients with HIE at the first day increased significantly than those at the third day (p<0.05), the <WP=32>serum TNF-a level in patients with HIE at the third day didn’t have significance with those at the seventh day (p>0.05), so we can find that the serum TNF-a level increased significantly in patients with mild, moderate and severe group of HIE at the ealier period, and the serum TNF-a level increased by severity of illnesss, the serum TNF-a level of the mild group went down fastly. So the serum TNF-a level of the mild group may have protective function when neonates had brain injury, and the serum TNF-a level of neonates can contribute to diagnose illness and analyse severity of illnesss at the earlier period. The result show that the serum NSE level of the moderate and severe group in patients with HIE at the third day and seventh day after birth increased significantly than those in control group (p<0.01), while the serum NSE level of the mild group didn’t have significance with those in control group (P>0.05). Although the serum NSE level of the third and the seventh day is lower than that of the first day, the serum NSE level of the severe group at the first, third day and seventh days increased significantly than those in control group (P<0.01). There is no differece a更多还原