Effects Of Phthalate On Pulmonary Allergy Of Offspring During Intrauterin And Lactating Exposure

ObjectivePhthalate esters(DEHP)was exposed to infect Wistar rats during pregnancy and lactation to investigate the effects of DEHP maternal exposure on allergic reactions in the lungs of the offspring,in order to understand the immunotoxicity of DEHP and childhood asthma.MethodsEighteen healthy 2-month-old female Wistar rats were divided into three different dose groups.From 0 days of gestation(GD0),pregnant rats in each group were given 0,30 and 300 mg/(kg/d)DEHP to 21 after birth.Day(PND21)was weaned and a maternal DEHP exposure model was established.After the pups were born,one pup in each cage of different dose groups was sensitized by intraperitoneal injection of ovalbumin(OVA)in PND21 and PND28 and sensitized by continuous nasal infusion of PND32,PND33 and PND34.PND35 and non-sensitized The rats were taken together,including alveolar lavage fluid and lung tissue.The secretion of Th2 type cytokines interleukin(IL)-4,IL-5 and IL-13 in alveolar lavage fluid was detected by ELISA.The lung tissue was examined by HE and PAS to observe the pathological changes of allergic inflammation in lung tissue.Immunohistochemistry The expression change of the epithelial-derived factor IL-33 was examined.Results1.In the alveolar lavage fluid,the number of total inflammatory cells and eosinophils in the DEHP0+OVA group increased to(131.500±25.548)×10~4,(32.000±10.079)×10~4(P<0.05),DEHP30.The number of total inflammatory cells and eosinophils in the+OVA group increased to(156.167±17.994)×10~4,(16.331±6.667)×10~4,(P<0.05),and the total number of inflammatory cells and eosinophils in the DEHP300+OVA group increased.(172.167±19.994)×10~4,(55.000±17.018)×10~4(P<0.05).2.After adding different doses of DEHP and OVA,the expression of IL-4,IL-5 and IL-13 in DEHP0+OVA group increased to(38.401±6.594)pg/mL(P>0.05).(30.026±2.756)pg/mL(P<0.05),(13.806±4.355)pg/mL(P<0.05);DEHP30+OVA group IL-4,IL-5,IL-13 expression increased respectively to(57.733±7.293)pg/mL(P<0.05),(31.544±1.043)pg/mL(P>0.05),(18.068±1.497)pg/mL(P<0.05);DEHP300+OVA group IL-4,IL-5,IL-13 expression increased to(54.943±6.049)pg/mL(P>0.05),(32.377±3.739)pg/mL(P>0.05),(20.168±0.939)pg/mL(P<0.05).Pathological observation of lung tissue showed that there was no obvious allergic inflammatory reaction in the lung tissue of the DEHP+OVA group,but the lung tissue of each DEHP+OVA group had obvious allergic reaction and increased with the increase of DEHP dose.4.Immunohistochemistry showed that the expression of IL-33 in DEHP-only exposed group did not increase significantly,while the expression of IL-33 in DEHP+OVA group increased and there was a dose-response relationship.Conclusions1.Pregnancy and lactation DEHP exposure have a certain intensification of the effect to the offspring of the lung allergic symptoms2.DEHP after OVA sensitivity,has the role of promoting eosinophilic granulocytes,inflammatory factors、Th2 and IL-33 expression.