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

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