刘春枝，梅 花

RAGE、AQP5水平与新生儿呼吸窘迫综合征病情的相关性研究

刘春枝，梅 花

目的 探讨糖基化终末产物受体(receptor for advanced glycation end products, RAGE)和水通道蛋白5(aquaporin 5, AQP5)水平与新生儿呼吸窘迫综合征(respiratory distress syndrome of newborn， RDSN)病情的相关性。方法 选择我院2014年1月—2016年1月收治的RDSN 78例作为观察组，选择同期出生的正常新生儿78例作为对照组。比较两组RAGE和AQP5水平变化，分析病情严重程度、胎龄及预后与RAGE和AQP5水平的相关性。 结果 与对照组比较，观察组RAGE和AQP5水平显著升高，差异有统计学意义(P=0.000)。RAGE、AQP5水平与胎龄、病情严重程度紧密相关(P=0.000)。RAGE诊断RDSN预后不良的曲线下面积为0.775[95%可信区间(CI)为0.616～0.934,P=0.011]，AQP5诊断RDSN预后不良的曲线下面积为0.739(95%CI为0.580～0.899,P=0.027)。结论 RDSN患儿RAGE、AQP5水平显著升高，且与病情严重程度、胎龄及预后密切相关。

呼吸窘迫综合征，新生儿；糖基化终末产物受体；水通道蛋白5

新生儿呼吸窘迫综合征(respiratory distress syndrome of newborn， RDSN)是导致新生儿死亡的主要原因之一[1-2]，是由于肺表面活性物质缺乏导致肺泡不张、通气不足，进而引起全身炎症反应、多脏器功能衰竭，甚至死亡[3]。糖基化终末产物受体(receptor for advanced glycation end products, RAGE)为免疫球蛋白超家族中的一员，通过与配体结合，促进血管内皮功能失调、炎症瀑布等病理反应[4]。研究显示急性肺损伤患者RAGE显著升高，且病情越重RAGE水平越高[5-6]。水通道蛋白5(aquaporin 5, AQP5)参与细胞内、外水的分布，急性肺损伤时可表现为肺水肿和大量炎症因子渗出等[7]。因此，推测RAGE、AQP5与RDSN存在一定的关联性，但鲜有文献报道此问题。本文探讨RAGE和AQP5水平与RDSN病情的相关性，现将结果报告如下。

1 资料与方法

1.1 一般资料 选择我院2014年1月—2016年1月收治的RDSN 78例作为观察组，其中男43例，女35例；平均胎龄(38.74±2.16)周；出生时体重(3259.78±395.38)g。选择同期出生的正常新生儿78例作为对照组，其中男45例，女33例；平均胎龄(38.92±2.45)周；出生时体重(3249.93±384.28)g。两组性别、胎龄、体重等一般资料比较差异无统计学意义(P>0.05)，具有可比性。本研究通过我院伦理委员会批准，且所有新生儿父母均知情同意并签署知情同意书。

1.2 纳入及排除标准 纳入标准：①入院时发病时间不超过12 h；②为新生儿；③动脉血氧分压(PaO2)/吸入氧浓度(FiO2)<300，且排除其他原因引起的肺损伤；④父母同意参与本研究。排除标准：①先天性心脏病；②先天畸形；③肺炎；④败血症；⑤治疗期间转院或放弃治疗。

1.3 观察指标及检测方法 主要观察指标为RAGE和AQP5，次要观察指标为病情严重程度、胎龄和预后。入院后留取新生儿肘静脉血5 ml，离心去血浆置于-80℃冷藏箱冻存待检，使用酶联免疫吸附(enzyme linked immunosorbent assay, ELISA)法检测RAGE、AQP5水平。RAGE ELISA试剂盒及AQP5 ELISA试剂盒均购自美国安迪生物公司。

2 结果

2.1 两组RAGE、AQP5水平比较 与对照组比较，观察组RAGE、AQP5水平显著升高，差异均有统计学意义(P=0.000)，见表1。

表1 新生儿呼吸窘迫综合征与正常新生儿RAGE、AQP5水平比较

注：RAGE为糖基化终末产物受体，AQP5为水通道蛋白5

2.2 不同病情严重程度RDSN的RAGE、AQP5水平比较 本研究定义200

表2 不同病情严重程度的新生儿呼吸窘迫综合征RAGE、AQP5水平比较

注：RAGE为糖基化终末产物受体，AQP5为水通道蛋白5

2.3 不同胎龄RDSN的RAGE、AQP5水平比较 观察组早产儿23例，正常产儿28例，晚产儿27例。早产儿、正常产儿和晚产儿RAGE和AQP5水平差异均有统计学意义(P=0.000)，见表3。

表3 不同胎龄新生儿呼吸窘迫综合征RAGE、AQP5水平比较

注：RAGE为糖基化终末产物受体，AQP5为水通道蛋白5

2.4 RAGE、AQP5诊断RDSN预后不良的价值 RAGE诊断RDSN预后不良的曲线下面积为0.775[95%可信区间(CI)为0.616～0.934,P=0.011]，AQP5诊断RDSN预后不良的曲线下面积为0.739(95%CI为0.580～0.899,P=0.027)，见图1。

图1 RAGE、AQP5诊断新生儿呼吸窘迫综合征预后不良的价值RAGE为糖基化终末产物受体，AQP5为水通道蛋白5

3 讨论

呼吸窘迫综合征是导致新生儿死亡的主要病因，其病理改变为大量炎性因子渗出和肺水肿。近年研究显示RAGE、AQP5与急性肺损伤密切相关[8-9]。RAGE是一种多配体识别的受体，与配体结合可激活细胞信号传导，进而促进炎症反应等病理生理改变。急性肺损伤时，fl-RAGE分子溶解分化为RAGE，通过毛细血管进入血液循环，故急性肺损伤时RAGE水平显著升高[10-11]。RAGE水平升高，可促进新生儿体内炎症反应的爆发，加重呼吸窘迫综合征病情的严重程度，导致多脏器功能损伤，使机体内环境及细胞代谢紊乱，进而影响新生儿的正常生长发育，为预后不良的主要因素。RAGE是高糖状态下还原糖与蛋白质等形成的一种聚合物，具有不可逆性。马爽等[12]研究显示妊娠期糖尿病孕产妇RAGE水平明显升高，为新生儿临床预后不良的因素。本研究显示早产儿呼吸窘迫综合征RAGE水平显著升高，且RAGE诊断RDSN预后不良的曲线下面积为0.775。

AQP5与肺泡内液体清除率显著相关[8,13-14]，过度的炎症反应可致新生儿肝肾等脏器功能损伤，进而引发多脏器功能受损。Wu等[7]研究发现RDSN的AQP5水平显著升高，且与病情严重程度紧密相关。呼吸窘迫综合征导致AQP5水平升高的原因可能是AQP5位于肺泡Ⅰ型上皮细胞，肺损伤时肺泡Ⅰ型细胞大量受损，进而将AQP5释放入血[15]。然而，有研究显示肺损伤时AQP5 mRNA水平呈降低趋势，相关作用机制尚需进一步的临床和动物研究证实[8,14,16]。

Jabaudon等[5]研究显示RAGE水平与肺泡清除率呈负相关，与呼吸窘迫综合征病情严重程度呈正相关，与Gu等[6]研究结果一致。Wu等[7]纳入了43例RDSN和10例正常新生儿，发现RAGE水平在RDSN中显著增高，与病情严重程度呈正相关。本文研究显示，与对照组比较，观察组RAGE、AQP5水平显著升高，且RAGE、AQP5水平与胎龄、病情严重程度和预后密切相关。相关研究结果支持本研究，且本文的研究对象为新生儿，样本量大，具有一定的临床指导意义。提示临床对于疑诊呼吸窘迫综合征的新生儿应及时行RAGE、AQP5水平检测，有利于早期判断新生儿肺损伤情况，尽早救治，以改善预后。

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Correlation between Levels of Receptor for Advanced Glycation End Products and Aquaporin 5 with Severity of Neonatal Respiratory Distress Syndrome

LIU Chun-zhi, MEI Hua
(Department of Pediatrics, Affiliated Hospital of Inner Mongolia Medical University, Hohehot 010050, China)

Objective To investigate correlation between receptor for advanced glycation end products (RAGE) and aquaporin 5 (AQP5) with severity of neonatal respiratory distress syndrome (RDSN). Methods A total of 78 patients with RDSN admitted during January 2014 and January 2016 were selected as observation group;, and 78 healthy neonates at the same period were collected as control group. Changes of RAGE and AQP5 levels between the two groups were compared, and correlations among severity of the disease, gestational age and prognosis with RAGE and AQP5 levels were analyzed. Results Compared with those in control group, RAGE and AQP5 levels were significantly increased (P=0.000). RAGE and AQP5 levels were closely correlated with gestational age and severity of the disease (P=0.000). The area under curve of RAGE in diagnosis of unfavourable prognosis of RDSN was 0.775 (95% IC: 0.616-0.934,P=0.011); and the curve area of AQP5 in the diagnosis of in-hospital mortality in neonatal respiratory distress syndrome was 0.775 [95% confidence interval (CI): 0.616-0.934,P=0.011], while area under curve of AQP5 in diagnosis of unfavourable prognosis of RDSN was 0.739 (95% CI:0.580-0.899,P=0.027). Conclusion RAGE and AQP5 levels are significantly increased in RDSN neonates, and the levels are closely related to severity of the disease, gestational age and prognosis.

Respiratory distress syndrome, newborn; Receptor for advanced glycation end products; Aquaporin 5

内蒙古卫生厅医疗卫生科研计划项目(20100036)；内蒙古自治区自然科学基金项目(2011MS1111)

010050 呼和浩特，内蒙古医科大学附属医院儿科

梅花，E-mail:meihuayani@sina.com

R722.12

A

1002-3429(2017)06-0096-04

10.3969/j.issn.1002-3429.2017.06.034

2017-03-06 修回时间：2017-04-07)