Study On The Joint Toxicity Of DEHP And Lead On The Blood System Of Rats

Di-（2-ethylhexyl）phthalate is an important phthalate ester,which is widely used as plasticizer in production and life.Because of its wide range of pollution,high degree of pollution and large toxic effect,it has been widely concerned by scholars at home and abroad.Lead is a heavy metal with persistence and bioaccumulation.Because of the application of heavy metal industry and human activities such as automobile exhaust and sewage irrigation,it exists widely in the environment.Both can be exposed to the body through a variety of ways and are transported throughout the body,which may have an impact on the body’s blood system.In this study,SD rats were used as experimental animals.DEHP（0,10,100mg/kg）and lead acetate（0,5,50mg/kg）were selected to expose rats by gavage for 20 days in a3×3 factorial design.The effects of combined exposure of phthalate and heavy metals on the blood system of rats and its mechanism were studied from the aspects of blood routine examination,bone marrow cell apoptosis and cycle,cytokines and oxidative stress.The effect of DEHP combined with lead acetate exposure on the number of blood cells in rats was analyzed by blood routine test.The results showed that the combined exposure of DEHP and lead acetate reduced the number of leukocytes and lymphocytes,and increased the number of granulocytes and monocytes,but had no significant effect on the number of red blood cells.The combined effect was mainly antagonistic.With the increase of exposure time,the effect of DEHP combined with lead acetate on the number of blood cells also increased.The effects of combined exposure of DEHP and lead acetate on the blood system of SD rats were analyzed by detecting the organ coefficient of hematopoietic organs,apoptosis and cycle of bone marrow cells.The results of organ coefficient showed that the combined exposure of DEHP and lead acetate significantly reduced spleen coefficient,but had no significant effect on renal coefficient.The results of apoptosis of bone marrow cells showed that the apoptosis rate of bone marrow cells in each dose group was higher than that in the control group.The apoptosis rate of bone marrow cells in high dose combined exposure group（100mg/kg DEHP+50mg/kg lead acetate）was the highest,reaching 9.72%.5mg/kg lead acetate combined exposure group showed antagonistic effect,50mg/kg lead acetate combined exposure group showed synergistic effect.The results of bone marrow cell cycle test showed that the combined exposure of DEHP and lead acetate could increase the ratio of G₁ phase cells and decrease the ratio of S phase and G₂ phase cells,indicating that the combined exposure of DEHP and lead acetate could induce G₁ phase arrest of bone marrow cells;the interaction of combined exposure on rat bone marrow cell cycle was antagonistic.Enzyme linked immunosorbent assay（ELISA）and spectrophotometry were used to analyze the effects of DEHP combined with lead acetate on cytokines and oxidative stress indexes in rats.The results of ELISA showed that compared with the control group,the serum interleukin-6 content was increased by 43%,TNF-αcontent was increased by 37%,interferon-γcontent was decreased by 20%,and erythropoietin content was not significantly changed in the high-dose combined exposure group.The results of oxidative stress index showed that the activity of catalase in bone marrow cells and serum decreased by 34%and 62%,the activity of superoxide dismutase decreased by 58%and 30%,and the content of malondialdehyde increased by 54%and 109%in the high-dose combined exposure group,respectively.The combined effect was mainly antagonistic.These results indicate that DEHP combined with lead acetate exposure can affect the content of cytokines in serum of rats and induce oxidative stress response.In this study,the effects of combined exposure of DEHP and lead acetate on the body’s blood system and the mechanism of action were explored through in vivo experiments.Studies have shown that combined exposure of DEHP and lead acetate can induce oxidative stress in the body and affect the secretion of cytokines,and then lead to bone marrow cell apoptosis and G₁ phase arrest,resulting in changes in blood routine.The combined effects of DEHP and lead acetate exposure on the body were mainly antagonistic.The results of this study are helpful to further clarify the toxic effects of pollutants and provide certain theoretical guidance for the risk assessment of compound pollution.