神经型一氧化氮合酶与新生鼠胃肠道疾病的相关性

doi:10.20223/j.cnki.1000-8535.2025.05.007

摘要/Abstract

摘要： 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。

关键词: 神经型一氧化氮合酶, 胃, 幽门, 婴儿肥厚性幽门狭窄, 新生鼠

Abstract: 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．

Key words: neuronal nitric oxide synthase, stomach, pylorus, hypertrophic pyloric stenosis in infants, neonatal rat

胡家奇, 张又祥, 罗梅娟, 黄婉仪. 神经型一氧化氮合酶与新生鼠胃肠道疾病的相关性[J]. 广州医药, 2025, 56(5): 622-629.

HU Jiaqi, ZHANG Youxiang, LUO Meijuan, HUANG Wanyi. The relationship between neural nitric oxide synthase and gastrointestinal disease in neonatal rats[J]. Guangzhou Medical Journal, 2025, 56(5): 622-629.

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