中文摘要：

目的研究生命早期不同时间点应用抗生素对新生大鼠细胞因子辅助性T淋巴细胞（Th）1／Th2平衡的影响。方法24只新生SD大鼠，随机分为出生第2天抗生素组（2dCef组）、出生第7天抗生素组（7dCef组）和对照组，每组8只。分别于出生第2天、第7天开始腹腔注射头孢噻肟钠连续3d，对照组予等量磷酸盐缓冲液。第35天计数支气管肺泡灌洗液（BALF）中细胞分类；采用酶联免疫吸附法和实时荧光定量PCR法分别测定白细胞介素（IL）-12、γ-干扰素（IFN-γ）、IL-4、IL-5水平及mRNA的相对表达量。结果2dCef组BALF细胞总数、中性粒细胞、淋巴细胞较对照组和7dCef组明显增加（F=93．78、15．84、7．36，P均〈0．05）。抗生素组BALF、血清IL-12及BALF中IFN-γ表达较对照组显著下降（F=26．53、12．95、47．18，P均〈0．05），其中2dCef组较7dCef组下降更显著[（127．724±12．35）ng／L比（198．15±18．93）ng／L、（105．91±13．61）ng／L比（133．63±13.82）ng／L、（147．23±24．10）ng／L比（178．52±12．46）ng／L，P均〈0．05]；抗生素组肺脏中IL-12mRNA水平较对照组显著下降（F=33．60，P〈0．05），2dCef组较7dCef组降低更显著（0．073±0．023比0．093±0．028，P〈0．05）；抗生素组BALF、血清IL-4水平以及肺组织中IL-4mRNA表达增高（F=64．26、13．79、11．54，P均〈0．05），2dCef组较7dCef组增高更显著[（103．65±7．68）ng／L比（82．044±8．77）ng／L、（87．81±4．72）ng／L比（69．69±7．79）ng／L、（0．067±0．036）比（0．051±O．055），P均〈0．05]。BALF、血清和肺组织中的IL-5表达在3组间差异无统计学意义（F=0．50、0．75、0．08，P均〉0．05）。结论生命早期抗生素使用可影响免疫细胞在新生大鼠呼吸道的分布，促进机体细胞因子免疫向Th2方向偏移，且抗生素使用越早，影响越严重。

英文摘要：

Objective To identify the dynamic influence of antibiotics use on T helper cell （Th） 1/Th2 eyto- kine balance in neonatal rats in their early life. Methods Twenty - four newborn SD rats were randomly divided into 3 groups including 2dCef group,TdCef group and a control group （ n = 8）. SD rats at 2 or 7 days of age were injected Ce- fotaxime sodium intraperitoneally for 3 consecutive days. The control group was injected the same amount of phosphate buffer saline. Serum and bronchoaveolar lavage fluid （BALF） samples were collected on 35 days old and diffe-rential cell count in BALF was done. Enzyme linked immunosorbent was used to detect the concentration of interleukin（IL） - 12, interferon- γ（ IFN- γ） , IL- 4 and IL- 5 in serum and BALF, and real -time quantitative PCR was used to de- tect mRNA expression of those cytokines in lung tissues. Results The number of total cells, neutrophils, and lympho- eytes in Cefotaxime treated on 2nd day after birth were significantly higher than those in the controls and 7th day group （F = 93.78,15.84,7.36 ,all P 〈0.05）. For Thl cytokines detection： the IL- 12 secretion in BALF and serum and INF - γ secretion in BALF of the 2 antibiotic groups were lower than those in control group（ F = 26.53,12.95,47. 18, all P 〈 0.05） ,the decrease in 2dCef group were more obviously than 7dCef group I （127.72 ± 12.35） ng/L vs （198.15± 18.93） rig/L,（105.91 ±13.61） ng/Lvs （133.63 ±13.82） ng/L,（147.23 ±24.10） ng/Lvs （178.52 ±12.46） ng/L, all P 〈0. 051. The mRNA expression of IL - 12 in antibiotic groups were lower than those in control group （ F =33.60, P 〈 0. 05 ） , and the decrease in 2dCef group was more obvious than that in 7 dCef group （ 0. 073±0. 023 vs 0. 093 ± 0.028 ,P 〈0.05 ）. For the Th2 cytokines： the IL -4 secretion concentration and mRNA expression in the 2 antibiotic groups were higher than those in the control group （ BALF,serum and lung） （F =64.26,13.79,11.54 ,all P 〈0.05） ,the increase