预防医学2024,Vol.36Issue(1) :65-69.DOI:10.19485/j.cnki.issn2096-5087.2024.01.017

围产期苯并[a]芘暴露对仔鼠胰腺PDX-1、TFAM表达及线粒体DNA拷贝数的影响

Effects of perinatal exposure to benzo[a]pyrene on the expression of PDX-1 and TFAM in pancreas and mitochondrial DNA copy number in offspring rats

崔蓉 郑玉建 鲁英 夏力旦·阿力甫
预防医学2024,Vol.36Issue(1) :65-69.DOI:10.19485/j.cnki.issn2096-5087.2024.01.017

围产期苯并[a]芘暴露对仔鼠胰腺PDX-1、TFAM表达及线粒体DNA拷贝数的影响

Effects of perinatal exposure to benzo[a]pyrene on the expression of PDX-1 and TFAM in pancreas and mitochondrial DNA copy number in offspring rats

崔蓉 1郑玉建 1鲁英 2夏力旦·阿力甫1
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作者信息

  • 1. 新疆医科大学护理学院,新疆乌鲁木齐 830011
  • 2. 海南医学院,海南海口 570216
  • 折叠

摘要

目的 观察围产期苯并[a]芘(B[a]P)暴露对仔鼠胰腺十二指肠同源框-1(PDX-1)、线粒体转录因子A(TFAM)表达和线粒体DNA拷贝数的影响,探讨围产期B[a]P暴露对仔鼠胰腺功能的损伤.方法 40只孕鼠随机分为对照组、最低剂量组(2μg/kg)、低剂量组(200 μg/kg)、中剂量组(800 μg/kg)和高剂量组(1 600 μg/kg),每组8只.各染毒组孕1 d起采用B[a]P玉米油混合物0.2 mL/100 g体重灌胃,对照组采用相同剂量玉米油灌胃,每日1次,至产后3周.对3周龄仔鼠进行腹腔麻醉,取胰腺组织进行胰岛素免疫组化检测;检测PDX-1、TFAM的蛋白和mRNA表达量,以及线粒体DNA拷贝数;采用Spearman秩相关分析B[a]P暴露剂量与以上指标的相关性.结果 中、高剂量组胰岛素阳性面积比率和胰岛素平均光密度值低于对照组(均P<0.05);胰岛素阳性面积比率和胰岛素平均光密度值与B[a]P剂量呈负相关(rs=-0.826、-0.858,均P<0.05).高剂量组PDX-1和TFAM蛋白表达量低于对照组(均P<0.05);PDX-1和TFAM蛋白表达量与B[a]P剂量呈负相关(rs=-0.756、-0.799,均P<0.05).中、高剂量组PDX-1的mRNA表达量和线粒体DNA拷贝数低于对照组,高剂量组TFAM的mRNA表达量低于对照组(均P<0.05);PDX-1、TFAM的mRNA表达量和线粒体DNA拷贝数与B[a]P剂量呈负相关(rs=-0.722、-0.550、-0.840,均P<0.05).结论 围产期B[a]P暴露导致仔鼠胰腺功能损伤可能与PDX-1、TFAM及线粒体DNA拷贝数表达降低有关.

Abstract

Objective To observe the effects of perinatal exposure to benzo[a]pyrene(B[a]P)on the expression of pancre-atic duodenal homeobox-1(PDX-1)and mitochondrial transcription factor A(TFAM)and mitochondrial DNA copy num-ber in offspring mice,and to explore the role of maternal exposure to B[a]P in the pancreatic function damage of off-spring mice.Methods Forty pregnant rats were randomly divided into the control group,the lowest dose group(2 μg/kg),the low dose group(200 μg/kg),medium dose group(800 μg/kg)and high dose group(1 600 μg/kg),with 8 rats in each group.From day 1 of pregnancy,each exposed group was given 0.2 mL/100 g body weight of B[a]P and corn oil mixture by gavage once a day until 3 weeks after delivery,while the control group was given the same dose of corn oil.The pancreatic tissue of three-week-old mice were collected after abdominal anesthesia for insulin immunohistochem-ical detection.The protein and mRNA expression levels of PDX-1 and TFAM,as well as mitochondrial DNA copy num-ber were detected.Spearman rank correlation analysis was used to analyze the correlation between B[a]P exposure dose and the above indicators.Results The insulin-positive area ratio and average optical density of insulin in the medium and the high dose groups were significantly lower than those in the control group(all P<0.05).The insulin-positive ar-ea ratio and average optical density of insulin were negatively correlated with the B[a]P dose(rs=-0.862 and-0.858,both P<0.05).The protein expression levels of PDX-1 and TFAM in the high dose group were significantly low-er than those in the control group(both P<0.05).The protein expression levels of PDX-1 and TFAM were negatively correlated with the B[a]P dose(rs=-0.756 and-0.799,both P<0.05).The mRNA expression levels of PDX-1 and mito-chondrial DNA copy number in the medium and high dose groups were significantly lower than those in the control group,and the mRNA expression level of TFAM in the high dose group was significantly lower than that in the control group(all P<0.05).The mRNA expression levels of PDX-1,TFAM,and mitochondrial DNA copy number were negative-ly correlated with the B[a]P dose(rs=-0.722,-0.550 and-0.840,all P<0.05).Conclusion Perinatal exposure to B[a]P can induce the damage of islet β cells in offspring rats,which may be related to the decreased expression of PDX-1 and TFAM and the copy number of mitochondrial DNA.

关键词

苯并[a]芘/胰腺十二指肠同源框-1/线粒体转录因子A/线粒体DNA拷贝数

Key words

benzo[a]pyrene/PDX-1/TFAM/mitochondrial DNA

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基金项目

新疆维吾尔自治区自然科学基金项目(2021D01C244)

出版年

2024
预防医学
浙江省预防医学会

预防医学

CSTPCD
影响因子:1.002
ISSN:2096-5087
参考文献量18
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