中华实用儿科临床杂志
中華實用兒科臨床雜誌
중화실용인과림상잡지
Journal of Applied Clinical Pediatrics
2015年
11期
863-866
,共4页
胡润芳%袁方%郭盛%吴良霞%吴珉%徐敏%张建华
鬍潤芳%袁方%郭盛%吳良霞%吳珉%徐敏%張建華
호윤방%원방%곽성%오량하%오민%서민%장건화
抗生素滥用%生命早期%细胞因子平衡%支气管哮喘
抗生素濫用%生命早期%細胞因子平衡%支氣管哮喘
항생소람용%생명조기%세포인자평형%지기관효천
Antibiotics overuse%Early life%Cytokine balance%Asthma
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、y-干扰素(IFN-y)、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[(127.72±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-4 mRNA表达增高(F =64.26、13.79、11.54,p均＜0.05),2dCd组较7dCef组增高更显著[(103.65 ±7.68) ng/L比(82.04± 8.77) ng/L、(87.81±4.72) ng/L比(69.69 ±7.79) ng/L、(0.067 ±0.036)比(0.051 ±0.055),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.
目的 研究生命早期不同時間點應用抗生素對新生大鼠細胞因子輔助性T淋巴細胞(Th) 1/Th2平衡的影響.方法 24隻新生SD大鼠,隨機分為齣生第2天抗生素組(2dCef組)、齣生第7天抗生素組(7dCef組)和對照組,每組8隻.分彆于齣生第2天、第7天開始腹腔註射頭孢噻肟鈉連續3d,對照組予等量燐痠鹽緩遲液.第35天計數支氣管肺泡灌洗液(BALF)中細胞分類;採用酶聯免疫吸附法和實時熒光定量PCR法分彆測定白細胞介素(IL)-12、y-榦擾素(IFN-y)、IL-4、IL-5水平及mRNA的相對錶達量.結果 2dCef組BALF細胞總數、中性粒細胞、淋巴細胞較對照組和7dCef組明顯增加(F=93.78、15.84、7.36,P均＜0.05).抗生素組BALF、血清IL-12及BALF中IFN-γ錶達較對照組顯著下降(F=26.53、12.95、47.18,P均＜0.05),其中2dCef組較7dCef組下降更顯著[(127.72±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];抗生素組肺髒中IL-12mRNA水平較對照組顯著下降(F=33.60,P＜0.05),2dCef組較7dCef組降低更顯著(0.073±0.023比0.093±0.028,P＜0.05);抗生素組BALF、血清IL-4水平以及肺組織中IL-4 mRNA錶達增高(F =64.26、13.79、11.54,p均＜0.05),2dCd組較7dCef組增高更顯著[(103.65 ±7.68) ng/L比(82.04± 8.77) ng/L、(87.81±4.72) ng/L比(69.69 ±7.79) ng/L、(0.067 ±0.036)比(0.051 ±0.055),P均＜0.05].BALF、血清和肺組織中的IL-5錶達在3組間差異無統計學意義(F=0.50、0.75、0.08,P均＞0.05).結論 生命早期抗生素使用可影響免疫細胞在新生大鼠呼吸道的分佈,促進機體細胞因子免疫嚮Th2方嚮偏移,且抗生素使用越早,影響越嚴重.
목적 연구생명조기불동시간점응용항생소대신생대서세포인자보조성T림파세포(Th) 1/Th2평형적영향.방법 24지신생SD대서,수궤분위출생제2천항생소조(2dCef조)、출생제7천항생소조(7dCef조)화대조조,매조8지.분별우출생제2천、제7천개시복강주사두포새우납련속3d,대조조여등량린산염완충액.제35천계수지기관폐포관세액(BALF)중세포분류;채용매련면역흡부법화실시형광정량PCR법분별측정백세포개소(IL)-12、y-간우소(IFN-y)、IL-4、IL-5수평급mRNA적상대표체량.결과 2dCef조BALF세포총수、중성립세포、림파세포교대조조화7dCef조명현증가(F=93.78、15.84、7.36,P균＜0.05).항생소조BALF、혈청IL-12급BALF중IFN-γ표체교대조조현저하강(F=26.53、12.95、47.18,P균＜0.05),기중2dCef조교7dCef조하강경현저[(127.72±12.35) ng/L비(198.15±18.93) ng/L、(105.91±13.61) ng/L비(133.63 ±13.82) ng/L、(147.23 ±24.10) ng/L비(178.52±12.46) ng/L,P균＜0.05];항생소조폐장중IL-12mRNA수평교대조조현저하강(F=33.60,P＜0.05),2dCef조교7dCef조강저경현저(0.073±0.023비0.093±0.028,P＜0.05);항생소조BALF、혈청IL-4수평이급폐조직중IL-4 mRNA표체증고(F =64.26、13.79、11.54,p균＜0.05),2dCd조교7dCef조증고경현저[(103.65 ±7.68) ng/L비(82.04± 8.77) ng/L、(87.81±4.72) ng/L비(69.69 ±7.79) ng/L、(0.067 ±0.036)비(0.051 ±0.055),P균＜0.05].BALF、혈청화폐조직중적IL-5표체재3조간차이무통계학의의(F=0.50、0.75、0.08,P균＞0.05).결론 생명조기항생소사용가영향면역세포재신생대서호흡도적분포,촉진궤체세포인자면역향Th2방향편이,차항생소사용월조,영향월엄중.
Objective To identify the dynamic influence of antibiotics use on T helper cell(Th) 1/Th2 cytokine balance in neonatal rats in their early life.Methods Twenty-four newborn SD rats were randomly divided into 3 groups including 2dCef group,7dCef group and a control group (n =8).SD rats at 2 or 7 days of age were injected Cefotaxime 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 detect mRNA expression of those cytokines in lung tissues.Results The number of total cells,neutrophils,and lymphocytes 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 -γsecretion 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 [(127.72 ± 12.35) ng/L vs (198.15 ± 18.93) ng/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 ＜0.05].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 in 2dCef group was more obvious than that in 7dCef group[(103.65 ± 7.68) ng/L vs (82.04 ± 8.77) ng/L,(87.81 ± 4.72) ng/L vs (69.69 ± 7.79) ng/L,(0.067 ± 0.036) ng/L vs (0.051 ± 0.055),all P ＜ 0.05];however,no significant differences of IL-5 either mRNA or cytokine secretion being detected among these 3 groups (F =0.50,0.75,0.08,all P ＞ 0.05).Conclusions Antibiotic use during early time of neonate rats alters postnatal immune cells distribution in the lung and promotes the shift in cytokine balance towards a Th2 profile,and the earlier the antibiotic use,the more serious the impact.
