目的 观察低出生体重早产儿应用抗生素后肠道菌群的动态变化。方法 选取2018年6月—2019年7月在广州市第一人民医院住院的10名低出生体重早产儿,在出生时、出生后1~2周、出生后2~3周、出生后3~4周、出生后4~5周、出生后5~6周时分别收集粪便样本,通过16s高通量测序检测患儿粪便菌群变化并统计分析。结果 应用抗生素后的低出生体重早产儿肠道菌群α多样性(Shannon指数、Simpson指数、ACE指数和PD_whole_tree指数)下降(P均<0.05),肠道菌群结构在门、科、属水平均发生改变,其中Alistipes、Bacteroides、Lactobacillus、unidentified_Lachnospiraceae、unidentified_Ruminococcaceae、Alloprevotella、unidentified_Cyanobacteria、Bacillus、Stenotrophomonas和Acinetobacter菌属相对丰度减少(P均<0.05)。结论 低出生体重早产儿应用抗生素后肠道菌群多样性下降,肠道菌群结构发生改变,并在抗生素停用后仍持续,针对性补充益生菌或益生元可能有助于肠道菌群恢复稳态。

Objective To observe the dynamic changes of gut microbiota in premature infants with low birth weight after antibiotics therapy. Methods 10 low birth weight premature infants hospitalized in Guangzhou First People's Hospital from June 2018 to July 2019 were included. Fecal samples were collected at birth, 1~2 weeks after birth, 2~3 weeks after birth, 3~4 weeks after birth, 4~5 weeks after birth and 5~6 weeks after birth, respectively. The changes of fecal microbiota were detected and analyzed by 16s high-throughput sequencing. Results The α-diversity of gut microbiota (Shannon index, Simpson index, ACE index and PD_whole_tree index) in low birth weight preterm infants treated with antibiotics decreased (P<0.05). The structure of gut microbiota changed at phylum, family and genus levels, among which Alistipes, Bacteroides, Lactobacillus, unidentified_Lachnospiraceae, unidentified_Ruminococcaceae, Alloprevotella, unidentified_Cyanobacteria, Bacillus, Stenotrophomonas and Acinetobacter decreased (P<0.05). Conclusion The diversity of gut microbiota in low birth weight preterm infants decreased and the structure of gut microbiota changed after antibiotic therapy. Targeted supplementation of probiotics or prebiotics may contribute to the recovery of gut microbial homeostasis.

      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．