孕期和哺乳期PM2.5气管暴露对子代小鼠主要脏器发育的影响及槲皮素的干预效果研究
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摘要
目的探讨孕期和哺乳期PM2.5气管暴露对子代小鼠主要脏器发育的影响及槲皮素的干预效果。方法将北京大学医学部实验动物科学部提供健康成年SPF级ICR孕鼠60只随机分为空白对照组、PM2.5模型对照组和低、中、高三个槲皮素干预组,每组12只。于孕3、6、9、12、15天和产后2、5、8、11、14、17天分别进行气管滴注,除空白对照组外,其余各组均滴注PM2.5溶液(15 mg/kg),空白组给予相应剂量的干净滤膜洗脱液;各组孕鼠于孕期和哺乳期每天灌胃,空白对照组和PM2.5模型组给予0.15%羧甲基纤维素钠灌胃,槲皮素三个干预组分别予以50 mg/kg、100 mg/kg、200 mg/kg的槲皮素羧甲基纤维素钠混悬液灌胃。所有孕鼠自然生产,并记录生产仔鼠只数及性别。于产后3天调窝至每窝6只仔鼠,雌雄各半,于产后21天处死母鼠,并于生后3天、10天、21天、5周每窝仔鼠分别处死一雌一雄,摘取脏器(心、肝、脾、肺、肾)并称重,并计算脏器系数,同时测量肠道长度。结果四个时间点仔鼠的脏器重量和系数模型组和空白组之间差异有统计学意义,尤其表现为心、脾、肾,而槲皮素低、中剂量组与PM2.5模型组相比表现出一定的干预作用。PM2.5模型组仔鼠生后10天、21天及5周的小肠长度显著小于空白对照组(P<0.05)。结论孕期及哺乳期PM2.5气管暴露对子代小鼠的心、脾、肾重量和脏器系数产生影响,并且使得子代小鼠小肠长度变短。孕期和哺乳期进行50 mg/kg和100 mg/kg的槲皮素干预可以在一定程度上减少PM2.5的上述发育损害。
Objective To investigate the influence of PM2. 5 tracheal exposure on organ development in mice and the interventive effect of quercetin during gestation and lactation. Methods 60 SPF Pregnant mice of Institute of Cancer Research,which provided by Peking University of Health Science Center,were randomly divided into 5 groups with 12 mice each group,including control group,PM2. 5 model group,and 3 quercetin intervention groups( Low,middle,and high dose group). Pregnant mice in all groups but the control group,were exposed to PM2. 5 suspension( 15. 0 mg/kg) by intratracheal instillation on gestational day 3,6,9,12,15 and lactation day 2,5,8,11,14,17 respectively. The control dams were administered with same amount of suspension from extracts of "blank " filter on the same time points.Meanwhile,each dam was given 0. 15% carboxymethylcellulose sodium( CMC) in control group and PM2. 5 model group,and different doses( 50,100,200 mg/kg) of quercetin in the 3 quercetin intervention groups by gavage once a day during gestational and lactation. Quercetin was suspended in 0. 15% CMC. All dams were allowed to natural labor and numbers of offspring and gender were recorded. On lactation day 3,6 offspring per litter with each sex of 3 were kept. One male and one female offspring from each litter were sacrificed on lactation day 3,10,21,35,and organs( heart,liver,spleen,lung,kidney) were weighted and the intestinal tract length was measured. Results There were significant differences between PM2. 5 model group and control group with the weight and coefficient of major organs at the four time points,especially for heart,spleen and kidney. Low and middle-dosed quercetin intervention group showed protective effect compared to PM2. 5 model group. In addition,the small intestine length in PM2. 5 model group was significantly shorter than control group in lactation day 10,21,and 35. Conclusion Mice exposed to PM2. 5 during gestation and lactation could reduce the weight and coefficient of major organs,including heart,spleen and kidney and small intestine length of the offspring. 50 and 100 mg/kg of quercetin administration during gestation and lactation might protect the dams against the adverse effects.
Objective To investigate the influence of PM2. 5 tracheal exposure on organ development in mice and the interventive effect of quercetin during gestation and lactation. Methods 60 SPF Pregnant mice of Institute of Cancer Research,which provided by Peking University of Health Science Center,were randomly divided into 5 groups with 12 mice each group,including control group,PM2. 5 model group,and 3 quercetin intervention groups( Low,middle,and high dose group). Pregnant mice in all groups but the control group,were exposed to PM2. 5 suspension( 15. 0 mg/kg) by intratracheal instillation on gestational day 3,6,9,12,15 and lactation day 2,5,8,11,14,17 respectively. The control dams were administered with same amount of suspension from extracts of "blank " filter on the same time points.Meanwhile,each dam was given 0. 15% carboxymethylcellulose sodium( CMC) in control group and PM2. 5 model group,and different doses( 50,100,200 mg/kg) of quercetin in the 3 quercetin intervention groups by gavage once a day during gestational and lactation. Quercetin was suspended in 0. 15% CMC. All dams were allowed to natural labor and numbers of offspring and gender were recorded. On lactation day 3,6 offspring per litter with each sex of 3 were kept. One male and one female offspring from each litter were sacrificed on lactation day 3,10,21,35,and organs( heart,liver,spleen,lung,kidney) were weighted and the intestinal tract length was measured. Results There were significant differences between PM2. 5 model group and control group with the weight and coefficient of major organs at the four time points,especially for heart,spleen and kidney. Low and middle-dosed quercetin intervention group showed protective effect compared to PM2. 5 model group. In addition,the small intestine length in PM2. 5 model group was significantly shorter than control group in lactation day 10,21,and 35. Conclusion Mice exposed to PM2. 5 during gestation and lactation could reduce the weight and coefficient of major organs,including heart,spleen and kidney and small intestine length of the offspring. 50 and 100 mg/kg of quercetin administration during gestation and lactation might protect the dams against the adverse effects.
引文
1郭宇宏,迪丽努尔·塔力甫,康宏,等.新疆部分城市可吸入颗粒物的浓度及粒径分布.环境科学与技术,2012,35:240-244.
2 Cohen AJ,Brauer M,Burnett R,et al.Estimates and 25-year trends of the global burden of disease attributable to ambient air pollution:an analysis of data from the Global Burden of Diseases Study 2015.Lancet,2017,389:1907-1918.
3 Liu A,Qian N,Yu H,et al.Estimation of disease burdens on preterm births and low birth weights attributable to maternal fine particulate matter exposure in Shanghai,China.Sci Total Environ,2017,609:815-821.
4 Li X,Huang S,Jiao A,et al.Association between ambient fine particulate matter and preterm birth or term low birth weight:An updated systematic review and meta-analysis.Environ Pollut,2017,227:596-605.
5 Wang H,Peng X,Cao F,et al.Cardiotoxicity and Mechanism of Particulate Matter 2.5(PM2.5)Exposure in Offspring Rats During Pregnancy.Med Sci Monit,2017,23:3890-3896.
6 Delfino RJ,Staimer N,Tjoa T,et al.Airway inflammation and oxidative potential of air pollutant particles in a pediatric asthma panel.J Expo Sci Environ Epidemiol,2013,23:466-473.
7 Pei Y,Jiang R,Zou Y,et al.Effects of Fine Particulate Matter(PM2.5)on Systemic Oxidative Stress and Cardiac Function in Apo E(-/-)Mice.Int J Environ Res Public Health,2016,13.
8 Gruse J,Kanitz E,Weitzel JM,et al.Quercetin Feeding in Newborn Dairy Calves Cannot Compensate Colostrum Deprivation:Study on Metabolic,Antioxidative and Inflammatory Traits.PLo S One,2016,11:e146932.
9 Willhite CC.Teratogenic potential of quercetin in the rat.Food Chem Toxicol,1982,20:75-79.
10 Lim SS,Vos T,Flaxman AD,et al.A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions,1990-2010:a systematic analysis for the Global Burden of Disease Study 2010.Lancet,2012,380:2224-2260.
11 Sun X,Luo X,Zhao C,et al.The association between fine particulate matter exposure during pregnancy and preterm birth:a metaanalysis.BMC Pregnancy Childbirth,2015,15:300.
12 Fleisch AF,Rifas-Shiman SL,Koutrakis P,et al.Prenatal exposure to traffic pollution:associations with reduced fetal growth and rapid infant weight gain.Epidemiology,2015,26:43-50.
13 Dadvand P,Parker J,Bell ML,et al.Maternal exposure to particulate air pollution and term birth weight:a multi-country evaluation of effect and heterogeneity.Environ Health Perspect,2013,121:267-373.
14 Lertxundi A,Baccini M,Lertxundi N,et al.Exposure to fine particle matter,nitrogen dioxide and benzene during pregnancy and cognitive and psychomotor developments in children at 15 months of age.Environ Int,2015,80:33-40.
15 Xu X,Yavar Z,Verdin M,et al.Effect of early particulate air pollution exposure on obesity in mice:role of p47phox.Arterioscler Thromb Vasc Biol,2010,30:2518-2527.
16 Seiva FR,Chuffa LG,Braga CP,et al.Quercetin ameliorates glucose and lipid metabolism and improves antioxidant status in postnatally monosodium glutamate-induced metabolic alterations.Food Chem Toxicol,2012,50:3556-3561.
17张凯,李兴杰,杨蔚,等.兰州市城关区采暖期大气PM_(2.5)成份分析及对子代小鼠的影响研究.冰川冻土,2016,38:1718-1723.
18 Liu Y,Wang L,Wang F,et al.Effect of Fine Particulate Matter(PM(2.5))on Rat Placenta Pathology and Perinatal Outcomes.Med Sci Monit,2016,22:3274-3280.
19 Zheng Z,Zhang X,Wang J,et al.Exposure to Fine Airborne Particulate Matters Induces Hepatic Fibrosis in Murine Models.JHepatol,2015,63:1397-1404.
20 Aztatzi-Aguilar OG,Uribe-Ramírez M,Narváez-Morales J,et al.Early kidney damage induced by subchronic exposure to PM(2.5)in rats.Part Fibre Toxicol,2016,13:68.
21 Liu W,Zhang M,Feng J,et al.The Influence of Quercetin on Maternal Immunity,Oxidative Stress,and Inflammation in Mice with Exposure of Fine Particulate Matter during Gestation.Int J Environ Res Public Health,2017,14:592.
22黄春喜,袁建敏,周向梅.牛磺酸对断奶小鼠小肠发育的影响.中国农业大学学报,2014,19:129-136.
2 Cohen AJ,Brauer M,Burnett R,et al.Estimates and 25-year trends of the global burden of disease attributable to ambient air pollution:an analysis of data from the Global Burden of Diseases Study 2015.Lancet,2017,389:1907-1918.
3 Liu A,Qian N,Yu H,et al.Estimation of disease burdens on preterm births and low birth weights attributable to maternal fine particulate matter exposure in Shanghai,China.Sci Total Environ,2017,609:815-821.
4 Li X,Huang S,Jiao A,et al.Association between ambient fine particulate matter and preterm birth or term low birth weight:An updated systematic review and meta-analysis.Environ Pollut,2017,227:596-605.
5 Wang H,Peng X,Cao F,et al.Cardiotoxicity and Mechanism of Particulate Matter 2.5(PM2.5)Exposure in Offspring Rats During Pregnancy.Med Sci Monit,2017,23:3890-3896.
6 Delfino RJ,Staimer N,Tjoa T,et al.Airway inflammation and oxidative potential of air pollutant particles in a pediatric asthma panel.J Expo Sci Environ Epidemiol,2013,23:466-473.
7 Pei Y,Jiang R,Zou Y,et al.Effects of Fine Particulate Matter(PM2.5)on Systemic Oxidative Stress and Cardiac Function in Apo E(-/-)Mice.Int J Environ Res Public Health,2016,13.
8 Gruse J,Kanitz E,Weitzel JM,et al.Quercetin Feeding in Newborn Dairy Calves Cannot Compensate Colostrum Deprivation:Study on Metabolic,Antioxidative and Inflammatory Traits.PLo S One,2016,11:e146932.
9 Willhite CC.Teratogenic potential of quercetin in the rat.Food Chem Toxicol,1982,20:75-79.
10 Lim SS,Vos T,Flaxman AD,et al.A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions,1990-2010:a systematic analysis for the Global Burden of Disease Study 2010.Lancet,2012,380:2224-2260.
11 Sun X,Luo X,Zhao C,et al.The association between fine particulate matter exposure during pregnancy and preterm birth:a metaanalysis.BMC Pregnancy Childbirth,2015,15:300.
12 Fleisch AF,Rifas-Shiman SL,Koutrakis P,et al.Prenatal exposure to traffic pollution:associations with reduced fetal growth and rapid infant weight gain.Epidemiology,2015,26:43-50.
13 Dadvand P,Parker J,Bell ML,et al.Maternal exposure to particulate air pollution and term birth weight:a multi-country evaluation of effect and heterogeneity.Environ Health Perspect,2013,121:267-373.
14 Lertxundi A,Baccini M,Lertxundi N,et al.Exposure to fine particle matter,nitrogen dioxide and benzene during pregnancy and cognitive and psychomotor developments in children at 15 months of age.Environ Int,2015,80:33-40.
15 Xu X,Yavar Z,Verdin M,et al.Effect of early particulate air pollution exposure on obesity in mice:role of p47phox.Arterioscler Thromb Vasc Biol,2010,30:2518-2527.
16 Seiva FR,Chuffa LG,Braga CP,et al.Quercetin ameliorates glucose and lipid metabolism and improves antioxidant status in postnatally monosodium glutamate-induced metabolic alterations.Food Chem Toxicol,2012,50:3556-3561.
17张凯,李兴杰,杨蔚,等.兰州市城关区采暖期大气PM_(2.5)成份分析及对子代小鼠的影响研究.冰川冻土,2016,38:1718-1723.
18 Liu Y,Wang L,Wang F,et al.Effect of Fine Particulate Matter(PM(2.5))on Rat Placenta Pathology and Perinatal Outcomes.Med Sci Monit,2016,22:3274-3280.
19 Zheng Z,Zhang X,Wang J,et al.Exposure to Fine Airborne Particulate Matters Induces Hepatic Fibrosis in Murine Models.JHepatol,2015,63:1397-1404.
20 Aztatzi-Aguilar OG,Uribe-Ramírez M,Narváez-Morales J,et al.Early kidney damage induced by subchronic exposure to PM(2.5)in rats.Part Fibre Toxicol,2016,13:68.
21 Liu W,Zhang M,Feng J,et al.The Influence of Quercetin on Maternal Immunity,Oxidative Stress,and Inflammation in Mice with Exposure of Fine Particulate Matter during Gestation.Int J Environ Res Public Health,2017,14:592.
22黄春喜,袁建敏,周向梅.牛磺酸对断奶小鼠小肠发育的影响.中国农业大学学报,2014,19:129-136.