吉林大学学报(医学版) ›› 2021, Vol. 47 ›› Issue (6): 1347-1352.doi: 10.13481/j.1671-587X.20210602

• 基础研究 • 上一篇    下一篇

小鼠孕期七氟醚暴露对后代母系行为学的影响及氢气的保护机制

黄代强1,刘朋飞2,何建斌1,孙静雪1,袁琳1,袁静1(),赵雷2()   

  1. 1.深圳市人民医院 暨南大学第二临床医学院 南方科技大学第一附属医院麻醉科,广东 深圳 518020
    2.深圳市人民医院 暨南大学第二临床医学院 南方科技大学第一附属医院日间手术中心,广东 深圳 518020
  • 收稿日期:2021-04-16 出版日期:2021-11-28 发布日期:2021-12-14
  • 通讯作者: 袁静,赵雷 E-mail:1120138479@qq.com;zhaoleicx@126.com
  • 作者简介:黄代强(1985-),男,四川省德阳市人,主治医师,医学硕士,主要从事麻醉与认知功能方面的研究。
  • 基金资助:
    国家自然科学基金项目(31900547);广东省深圳市知识创新计划项目(JCYJ20180228164500540);广东省深圳市“孔雀计划”项目(KQTD2016113015442590)

Effect of sevoflurane exposure during pregnancy period on maternal behavior of offspring of mice and protection mechanism of H2

Daiqiang HUANG1,Pengfei LIU2,Jianbin HE1,Jingxue SUN1,Lin YUAN1,Jing YUAN1(),Lei ZHAO2()   

  1. 1.Department of Anesthesiology,Shenzhen People’s Hospital,Second Clinical Medical College,Jinan University,First Affiliated Hospital,Southern University of Science and Technology,Shenzhen 518020,China
    2.Ambulatory Surgical Center,Shenzhen People’s Hospital,Second Clinical Medical College,Jinan University,First Affiliated Hospital,Southern University of Science and Technology,Shenzhen 518020,China
  • Received:2021-04-16 Online:2021-11-28 Published:2021-12-14
  • Contact: Jing YUAN,Lei ZHAO E-mail:1120138479@qq.com;zhaoleicx@126.com

摘要: 目的

观察小鼠孕期七氟醚暴露对后代母系行为学变化的影响,并探讨其可能的作用机制。

方法

将怀孕15~16 d的40只C57BL/6小鼠随机分为正常对照组、2%七氟醚组、2%七氟醚+1% 氢气(H2)组和2%七氟醚+4% H2组,每组10只。以50% 氧气(O2)+ 50% 氮气(N2)的混合气体为载气,各组处理时间均为6 h·d-1,连续处理3 d后,各组孕鼠继续喂养。观察各组1代母鼠的做窝质量评分、母鼠第一次去嗅幼崽时间、幼崽取回放入窝内的时间和幼崽交换抚育成活率,ELISA法检测各组小鼠血浆中催产素和血管加压素水平,Western blotting法检测1代小鼠下丘脑内侧视前区组织中c-Fos癌基因 (c-Fos)、多聚ADP核糖聚合酶1(PARP1)、剪切的多聚ADP核糖聚合酶1(cleaved PARP1)、Caspase 3和剪切的Caspase 3(cleaved Caspase 3)蛋白表达水平。

结果

母系行为学观察,各组均未见需要采用牛奶喂养的2代幼崽和不清洁的2代幼崽,各组母鼠的做窝质量评分比较差异无统计学意义(P>0.05)。2%七氟醚组母鼠第1次去嗅幼崽时间和将幼崽取回放入窝内的时间明显长于正常对照组(P<0.05)。与2%七氟醚组比较,2%七氟醚+1% H2组母鼠第1次去嗅幼崽时间和将幼崽取回放入窝内的时间明显缩短(P<0.05),2%七氟醚 +4% H2组母鼠第1次去嗅幼崽时间和将幼崽取回放入窝内所用时间与正常对照组比较差异无统计学意义(P>0.05)。各组孕鼠血浆中催产素和血管加压素水平比较差异无统计学意义(P>0.05)。各组1代小鼠下丘脑内侧视前区组织中c-Fos、PARP1、cleaved PARP1、Caspase 3和cleaved Caspase 3蛋白表达水平比较差异无统计学意义(P>0.05)。

结论

小鼠孕期暴露于临床剂量的七氟醚不会显著影响下丘脑内侧视前区细胞的凋亡情况,但对小鼠的母系行为造成了一定的影响;对七氟醚介导的母系行为学异常,H2具有一定的保护作用。

关键词: 胎儿期, 七氟醚, 母系行为, 细胞凋亡, H2保护

Abstract: Objective

To observe the effect of the sevoflurane exposure during pregnancy period on changes of the maternal behaviors of the offsprings of the mice, and to explore its possible mechanism.

Methods

Forty pregnant C57BL / 6 mice(gestational age: 15-16 d) were randomly divided into normal control group, 2% sevoflurane group, 2% sevoflurane + 1% H2 group and 2% sevoflurane + 4% H2 group, and there were 10 mice in each group. The mixed gas of 50% O2 + 50% N2 was used as the carrier gas. The treatment time of the mice in each group was 6 h·d-1. After continuous treatment for 3 d,the pregnant mice in various groups were continued to be fed. The score of nest quality of the 1st-generation mice, the time of the mother mice to first sniff the pups, the time to retrieve the pubs and put into the nest and the survival rates of 2nd-generation exchange pups in various groups were observed. The levels of oxytocin and vasopressin in plasma of the mice in various groups were detected by ELISA method. The expression levels of c-Fos proto-oncogene (c-Fos),poly ADP ribose polymerase 1 (PARP1),cleaved PARP1, Caspase 3,and cleaved Caspase 3 proteins in the medial preoptic area in hypothalamus tissue of the 1st-generation mice in various groups were detected by Western blotting method.

Results

The maternal behavioral observation results showed that there were no milk-fed-2nd-generation pups and unclean 2nd-generation pups in various groups. There was no significant difference in the scores of nest quality of the mother mice among various groups (P>0.05). The time of the mother mice to first sniff the pups and the time to retriev the pups and put into the nest in 2% sevoflurane group was significantly longer than those in normal control group (P<0.05). Compared with 2% sevoflurane group, the time of the mother mice to first sniff the pups and the time to retrieve the pups and put into the nest of the mice in 2% sevoflurane + 1% H2 group were significantly decreased (P<0.05). There were no significant differences in the time of the mother mice to first sniff the pups and the time to retrieve the pups and put into the nest of the mice between 2% sevoflurane + 4% H2 group and normal control group (P>0.05). There were no significant differences in the plasma levels of oxytocin and vasopressin of the pregnant mice among various groups (P>0.05). There were no significant differences in the expression levels of c-Fos,PARP1, cleaved PARP1, Caspase 3,and cleaved Caspase 3 proteins in medial preoptic area in hypothalamus tissue of the 1st-generation mice among various groups (P>0.05).

Conclusion

The exposure to clinical doses of sevoflurane during pregnancy period of the mice could not significantly affect the apoptosis in the medial preoptic area in hypothalamus tissue, but it does have an impact on the maternal behavior of the mice. In addition, H2 has a protective effect against the sevoflurane-mediated abnormal maternal behavior.

Key words: fetal period, sevoflurane, maternal behavior, apoptosis, H2 protection

中图分类号: 

  • R714.5