上海交通大学学报（医学版）

上海交通大学学报（医学版）

• 论著（基础研究） • 上一篇    下一篇

孕期维生素D缺乏对子鼠Th1/Th2细胞免疫功能的影响

魏真真， 陈威威， 王磊， 余晓丹   

  1. 上海交通大学 医学院附属新华医院儿保科， 环境与儿童健康教育部和上海市重点实验室， 上海 200092
  • 出版日期:2016-09-28 发布日期:2016-10-31
  • 通讯作者: 余晓丹, 电子信箱: xd_yu2003@126.com。
  • 作者简介:魏真真(1990—)， 女， 硕士生; 电子信箱: zq744143217@126.com。
  • 基金资助:

    国家自然科学基金（81373004），上海市教育委员会高峰高原学科建设计划（20152220）

Effects of maternal vitamin D deficiency on the immune function of Th1/Th2 in offspring rats

WEI Zhen-zhen, CHEN Wei-wei, WANG Lei, YU Xiao-dan   

  1. Department of Child and Adolescent Healthcare, MOE-Shanghai Key Lab of Childrens Environmental Health, Xinhua Hospital ，Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
  • Online:2016-09-28 Published:2016-10-31
  • Supported by:

    National Natural Science Foundation of China, 81373004; Shanghai Municipal Education Commission—Gaofeng Clinical Medicine Grant Support, 20152220

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摘要：

目的·探讨孕期维生素D缺乏及补充对子鼠Th1/Th2免疫调节功能的影响。方法·48只8周龄雌性SD大鼠分为3组，对照组（C组）、维生素D缺乏组（VDD组）及维生素D补充组（VDS组）各16只。C组给予正常饲料，VDD组及VDS组给予维生素D缺乏饲料。喂养4周后按雌雄比2∶1合笼。妊娠成功后C组及VDS组给予正常饲料，VDD组继续予维生素D缺乏饲料。妊娠第10天(孕中期)用LC-MS/MS法检测维生素D水平。至子鼠4周龄时检测维生素D水平，采用流式细胞术检测Th1/Th2比例，ELISA法检测血浆中IFN-γ、IL-4表达水平。结果·C组、VDD组及VDS组孕鼠孕中期25(OH)D水平分别为（23.23±2.08）、（5.52±2.36）及（11.35±1.84）ng/mL；子鼠25(OH)D水平分别为(7.15±1.30)、(0.93±0.22)及(6.82±1.37)ng/mL；VDD组孕鼠及子鼠维生素D水平均明显低于C组和VDS组(P<0.05)。C组、VDD组及VDS组子鼠Th1/Th2细胞比例分别为0.90±0.35、0.24±0.08及0.94±0.26；与C组相比，VDD组Th1/Th2比例显著向Th2极化，而VDS组Th2极化有明显改善。C组、VDD组及VDS组IFN-γ水平分别为(18.72±5.66)、（8.27±3.86）及（19.31±5.68）pg/mL，IL-4水平分别为(3.49±0.52)、(4.14±0.55)及（3.52±0.52）pg/mL；与C组和VDS组相比，VDD组IFN-γ水平显著降低，IL-4水平显著升高（P<0.05）。结论·大鼠孕期维生素D缺乏可导致子代Th1/Th2向Th2极化，IFN-γ/IL-4向IL-4漂移。补充维生素D后子代Th2极化和IL-4漂移得到明显改善。

关键词: 孕期；维生素D；Th1/Th2细胞比例；IFN-&gamma, ；IL-4

Abstract:

Objective·To investigate the effects of maternal vitamin D deficiency and supplementation on the immunomodulatory function of Th1/Th2 in offspring rats. Methods·Forty-eight female SD (8-week-old) rats were randomly assigned to three groups, i.e control group (C group, n=16), vitamin D deficiency group (VDD group, n=16), and vitamin D supplementation group (VDS group, n=16). C group was fed a normal diet and VDD and VDS groups were fed a vitamin D deficiency diet. After four weeks, females and males were housed in a 2∶1 ratio. After gestation, C group and VDS group were fed a normal diet and VDD group was still fed a vitamin D deficiency diet. The vitamin D level in female rats was measured using LC-MS/MS at gestational day 10 (second trimester). The vitamin D level, the ratio of Th1/Th2, and expressions of serum IFN-γ and IL-4 in offspring were measured using LC-MS/MS, flow cytometry, and ELISA 4 weeks after birth, respectively. Results·For C group, VDD group, and VDS group, the 25(OH)D levels in female rats were (23.23±2.08), (5.52±2.36), and (11.35±1.84) ng/mL, respectively, while the 25(OH)D levels in offspring were (7.15±1.30), (0.93±0.22), and (6.82±1.37) ng/mL, respectively. The 25(OH)D levels in female rats and their offspring of VDD group were significantly lower than those of C group and VDS group (P<0.05). The Th1/Th2 ratios in offspring of C group, VDD group, and VDS group were 0.90±0.35, 0.24±0.08, and 0.94±0.26, respectively. The Th1/Th2 ratio in VDD group was significantly polarized toward Th2 and polarization of Th2 in VDS group was remarkably improved compared with C group. The IFN-γ levels in C group, VDD group, and VDS group were (18.72±5.66), (8.27±3.86), and (19.31±5.68) pg/ml, and the IL-4 levels were (3.49±0.52), (4.14±0.55), and (3.52±0.52) pg/ml. The IFN-γ level significantly decreased and the IL-4 level significantly increased in VDD group compared with C group and VDS group (P<0.05). Conclusion·Vitamin D deficiency in pregnant rats caused the imbalance of Th1/Th2 (Th2 polarization) and IFN-γ/IL-4 (drifting toward IL-4) in offspring. Vitamin D supplementation significantly improved the imbalance of Th1/Th2 and IFN-γ/IL-4 in offspring.

Key words: pregnancy, vitamin D, the ratio of Th1/Th2, IFN-γ, IL-4