Effects of exposure time and dose of diethylhexyl phthalate on lung maturation in neonatal rats
Objective To investigate the effects of exposure time and dose of diethylhexyl phthalate(DEHP)on lung maturation in neonatal rats.Methods A total of 120 SD rats were stochastic divided into 4 groups with 30 rats in each group,which were control,low dose,medium dose and high dose group,respectively.The low-dose group was given 10 mg/kg DEHP,the medium-dose group was given 100 mg/kg DEHP,and the high-dose group was given 750 mg/kg DEHP.The amount of corn oil administered to the control group was the same as that given to the DEHP group.On the 14th day and the 21st day,15 rats in each group were randomly sacrificed,and lung tissues were taken for subsequent experiments.H-E staining was used to evaluate the pathological changes of lung tissue.The levels of lung maturation related proteins were evaluated by immuno-histochemistry.The expression of lung maturation related proteins was detected by immunohistochemical staining.Real-time fluorescence quantitative PCR was used to measure MMP-9,TIMP-1 and TGF-β mRNA expression levels.Results DEHP exposure resulted in decreased radial alveolar count(RAC)and increased mean alveolar diameter(MAD)and mean intercept(MLI)in newborn rats.Exposure to DEHP resulted in alveolar injury for 2 weeks,and prolonged exposure time to 3 weeks aggravated the alveolar injury,and the higher the dose,the more serious the alveolar injury.In terms of mRNA level and pro-tein level,with the increase of DEHP dose,the expression of MMP-9 and TIMP-1 increased gradually,and the expression of TGF-β decreased gradually.In addition,with the increase of DEHP exposure time,the expression of MMP-9 and TIMP-1 in-creased gradually,and the expression of TGF-β decreased gradually.Conclusion Exposure to diethylhexyl phthalate can affect the lung development of neonatal rats,and the increase of exposure dose and time can aggravate the lung development delay of neonatal rats.