目的 探讨分析氨茶碱治疗早产儿呼吸暂停的临床疗效及其在治疗过程中所出现的不良事件。方法 选取2014年9—2016年3月广州市第一人民医院新生儿科接受住院治疗的胎龄＜34周,生后2 h内入住新生儿科的早产儿42例。随机分为对照组和氨茶碱组,对照组(20例)给予保暖、吸氧、补充能量、保持呼吸道通畅、物理刺激等对症治疗,不使用氨茶碱及其它改善呼吸的药物;氨茶碱组(22例)患儿除给予对照组治疗措施外,同时给予氨茶碱静脉滴注,首剂负荷量5 mg/kg,在20min内完成,12 h后以2～2.5 mg/kg维持量,每隔12 h一次。观察两组的疗效与不良影响。结果 ①两组患儿性别、出生胎龄、出生体重、产前孕母糖皮质激素的应用、受孕方式、分娩方式、多胎妊娠、5min Apgar评分、机械通气及CPAP辅助通气例数、低-中流量吸氧(箱内或头罩给氧)例数等方面差异均无统计学意义(P均＞0.05)。②与对照组相比,氨茶碱组早产儿呼吸暂停(AOP)发生的次数较少,AOP消失所需时间较短,差异均有统计学意义(P＜0.05)。③不良影响方面,氨茶碱组脑白质发育不良发生率(63.6%,14/22例)显著高于对照组(25%,5/20例),差异有统计学意义(P＜0.05);两组患儿在听力检查异常、喂养不耐受、血糖紊乱、血脂代谢紊乱、血红蛋白下降、电解质紊乱、出院时体重及住院时间等方面均无统计学意义(P均＞0.05)。④氨茶碱组视网膜发育不完全的发生率(40.9%,9/22例)明显高于对照组(15.0%,3/20例),但差异无统计学意义(P＞0.05)。结论 小剂量氨茶碱在防治AOP方面的作用是值得肯定的,但它有可能增加早产儿脑白质发育不良的风险与视网膜发育不完全的风险。

Objective To investigate the clinical efficacy and adverse effects of aminophylline in prevention of apnea of prematurity. Methods Forty-two infants with gestational age ＜34 weeks admitted to department of pediatrics, Guangzhou first people's hospital between Sep. 2014 and Mar. 2016 were randomly divided into 2 groups: control group and aminophylline group. Control group(n=20): 20 infants received warming, oxygen inhalation, supplement energy, maintain airway patency, physical stimulation, such as symptomatic treatment, without aminophylline or any other drugs for improving breathing. Aminophylline group(n=22): In addition to the control group treatment measures, 22 infants received a loading dose of 5 mg/kg of aminophylline and then maintained by a dose of 2mg/kg with intravenous drip q 12 h. Then we compared the efficacy and adverse effects of the two groups. Results ①There was no significant difference in gender, gestational age, birth weight, maternal antenatal glucocorticoid application, pregnancy(including multiple pregnancy) and delivery,5 min Apgar score, oxygen therapy, the application of mechanical ventilation, nasal continuous positive airway pressure, and the low-medium flow oxygen inhalation between the 2 groups(all P＞0.05). ② Compared with the control group, the incidence of apnea in aminophylline group were significant lower, and the time needed for apnea to disappear were significant shorter(all P＞0.05). ③ The incidence of cerebral white matter development dysplasia of aminophylline group(63.6%,14/22 cases) were significant higher than the control group(25%,5/20 cases, P＜0.05). There was no statistically significant difference in hearing loss, feeding intolerance, blood glucose disturbance, blood lipid metabolism disorder, hemoglobin decrease, electrolyte disorder, body weight at discharge, the duration and cost of hospitalization between the 2 groups(all P＞0.05). ④ The incidence of retinal incompleted development of aminophylline group(40.9%, 9/22 cases) were higher than control group(15.0%, 3/20 cases), but there was no statistical significance between the 2 groups(P＞0.05). Conclusion Effects of aminophylline in treating apnea of prematurity is positive, but it is likely to increase the risk of premature brain white matter development dysplasia and the risk of retinal incompleted development.

      目的   探讨神经元型一氧化氮合酶（nNOS）在抑制剂N-硝基-左旋精氨酸甲酯（L-NAME）抑制作用下与新生鼠胃肠道疾病的相关性研究，以进一步研究婴儿肥厚性幽门狭窄（IHPS）等疾病的致病机制。方法   对40只成熟雌性wistar大鼠随机均分4组，怀孕后予怀孕母鼠灌胃，对照组给予生理盐水，低剂量组、中剂量组、高剂量组分别给予L-NAME 60、300、600 mg/（kg·d）L-NAME。新生鼠皮下注射方式，予对照组皮下注射生理盐水，在低剂量组、中剂量组、高剂量组皮下注射L-NAME 25、125、250 mg/（kg·d）L-NAME。统计分析新生鼠幽门中的nNOS表达量、体质量增长情况、胃潴留情况、幽门肌层厚度。结果 （1）低剂量组、中剂量组、高剂量组新生鼠幽门肌层厚度在出生后第1、7、14日龄高于对照组，但组间比较差异无统计学意义（P＞0.05）。（2）与对照组相比，低剂量组、中剂量组、高剂量组的新生鼠出生后第1周体质量增加量更少，胃潴留更明显（P＞0.05）；在出生后的第2周各组体质量增加量差异无统计学意义（P＞0.05）。（3）新生鼠出生后第14天，中剂量组的胃体积大于低剂量组，但低剂量组和对照组之间、中剂量组和高剂量组之间比较差异无统计学意义（P＞0.05）。（4）新生鼠生后第1天，幽门中nNOS的表达被L-NAME以剂量依赖的方式被抑制，随着新生鼠日龄的增长，这种效应逐渐消失。（5）在不同剂量L-NAME的作用下，新生鼠幽门中nNOS表达量、趋势在不同时间点不同。结论 （1）nNOS可以导致新生鼠胃潴留、幽门梗阻，与IHPS相关症状之间存在相关性，但可能不是IHPS病因的唯一分子机制。（2）在新生鼠胃、幽门组织中，nNOS的表达量可以通过负反馈调节机制调节。（3）nNOS表达量上调可能有助于幽门舒张，但可能无法完全逆转IHPS中幽门的进一步肥厚和阻塞。

    Objective  To explore the effect of nNOS on the early postnatal pylorus of neonatal rats under the inhibition of the inhibitor N-nitro-L-arginine methyl ester hydrochloride（L-NAME），in order to further investigate the pathogenic mechanism of infantile hypertrophic pyloric stenosis（IHPS）．Methods  Pregnant female mice were grouped randomly and administered by gavage，with the control group receiving physiological saline，the low-dose，medium-dose and high-dose groups  receiving different doses of L-NAME．For the neonatal rats，the control group was subcutaneously injected with physiological saline，while the low-dose group，medium-dose group，and high-dose group were subcutaneously injected with different doses of L-NAME．The expression of nNOS in the pylorus，weight gain，gastric retention，and pyloric muscle thickness of newborn  rats were statistically analyzed．Results   (1) The thickness of the pyloric muscle layer in the low-dose group，medium-dose group，and high-dose group of newborn rats was higher than that in the control group on the 1st，7th，and 14th day after birth，but there was no significant difference．（2）Compared with the control group，the neonatal rats in the low-dose group，the middle-dose group and the high-dose group gained less weight in the first week after birth，and the gastric retention was more significant．There was no significant difference in weight gain among the groups in the second week after birth．（3）On the 14th day after birth，the gastric volume of the medium-dose group was larger than that of the low-dose group，but there was no statistical difference between the low-dose group and the control group，or between the medium-dose group and the high-dose group．（4）On the first day after birth，the expression of nNOS in the pylorus of neonatal rats was significantly inhibited by L-NAME with dose-dependence，and this effect gradually disappeared with increasing age of neonatal rats．(5) Under the action of different doses of L-NAME，the expression level and trend of nNOS in the pylorus of neonatal mice vary at different time points．Conclusions   (1) nNOS can cause gastric  retention and pyloric obstruction in newborn rats，which is related to IHPS related symptoms，but may not be the only molecular mechanism of IHPS etiology．(2) The expression level of nNOS in the pyloric tissue of newborn mice can be regulated through a negative feedback regulatory mechanism．(3) Upregulation of nNOS expression may contribute to pyloric dilation，but may not completely  reverse thickening and obstruction of the pylorus in IHPS．