槲皮素对PM2.5发育毒性的拮抗作用

Protective effect of quercetin on in utero development after maternal exposure to PM2.5

目的研究槲皮素对PM2.5发育毒性的拮抗作用。方法收集2014年11月—2015年3月采暖期北京市某地区大气颗粒物样品于石英滤膜上,通过水浴超声和冷冻干燥操作收集石英滤膜上的PM2.5颗粒,以无菌PBS配制成不同浓度的PM2.5溶液。将健康ICR孕鼠随机分为空白对照组、PM2.5模型对照组、维生素C(VC)干预组和3个槲皮素干预组。除空白对照组的各组孕鼠于孕3、6、9、12、15天分别进行气管滴注PM2.5溶液(15 mg/kg),空白对照组给予相应剂量的干净滤膜洗脱液。各组孕鼠于孕0~17 d每天灌胃,空白对照组和PM2.5模型对照组给予0.15%羧甲基纤维素钠灌胃,VC干预组给予100 mg/kg的VC,槲皮素三个干预组分别予以50mg/kg、100 mg/kg、200 mg/kg的槲皮素羧甲基纤维素钠混悬液灌胃。各组孕鼠于孕18天处死,收集母鼠血液,检测血清中的过氧化氢酶(CAT)活力和谷胱甘肽(GSH)含量;称量活胎重量、胎盘重量、胎鼠身长和尾长,记录活胎数、死胎数和吸收胎数,并进行活胎骨骼和内脏畸形检查。结果与空白对照组相比,PM2.5模型对照组的胎鼠出生体重下降、胎鼠身长变短、14肋骨畸形发生率增加和枕骨骨化不全程度加重,同时母鼠血清CAT活力下降,差异均有统计学意义。与PM2.5模型对照组相比,槲皮素中剂量组的胎鼠体重和胎鼠身长改善效果最明显,表现为胎鼠体重增加和胎鼠身长增长;槲皮素低剂量组和中剂量组母鼠血清CAT活力显著升高;槲皮素干预组的枕骨骨化不全的情况得到明显改善。与PM2.5模型对照组相比,VC干预组的胚胎毒性加重及14肋骨畸形的发生率升高。结论孕期补充槲皮素对PM2.5引发的发育毒性具有一定的拮抗作用,且保护作用有适宜的剂量范围。

Objective To investigate the preventive effect of quercetin against the developmental toxicity of PM2.5.Methods PM2.5 were collected with quartz-filter in heating period in winter and the PM2.5 particles were processed as solutions for future use.ICR pregnant mice were randomly divided into 6 groups：the control group,the PM2.5 model control group,the VC intervention group,the low,middle,and high quercetin intervention groups.On the 3th,6th,9th,12th,and 15th gestational days （GD）,pregnant mice were given PBS and PM2.5 （15mg/kg） respectively by means of intratracheal instillation.From the GD 0 to the GD 17,pregnant mice were administrated with 0.15% sodium of carboxymethyl cellulose,VC （l00mg/kg）,or quercetin （50mg/kg,100mg/kg,200mg/kg）,respectively,by means of gavage.On GD 18,all the dams were killed,and blood samples were collected for further analysis.Fetal developmental indexes were observed.Results Compared with mice in the control group,offspring＆#39;s body weight and placenta weight of the PM2.5 model control group decreased,CAT activity decreased,the incidence of 14 rib malformation increased,and incomplete occipital ossification became worse,with all of the differences being statistically significant.Compared with mice in the PM2.5 model control group,offspring＇s body weight and placenta weight of the middle quercetin intervention group improved significantly （P 〈 0.05）;CAT activity in the low,middle quercetin intervention groups increased significantly （P 〈 0.05）;incomplete occipital ossification in the three intervention groups improved significantly （P 〈 0.05）.Compared with mice in the PM2.5 model control group,embryo toxicity and the incidence of 14 rib malformation in VC intervention group increased.Conclusion Quercetin has a significant protective effect against the developmental toxicity of PM2.5,and the protective effect has a suitable dose range.