Mechanism Of Allergic March Induced By Diisononyl Phthalate Via NF-?B/endoplasmic Reticulum Stress Pathway

At present,phthalic acid esters(PAEs)are man-made organic chemicals widely used in plasticizers to enhance the scalability and flexibility of industrial products.It is widely used in cosmetics,pesticides,insect repellents,floors,food packaging,toys and medical equipment,but because phthalates can cause various harmful effects such as liver and kidney toxicity,reproductive toxicity,etc.,their wide application also has potential harm to our body health.As a new type of environmental friendly plasticizer,diisononyl phthalate(DINP)is the environmentally friendly plasticizer with the best application prospects among PAEs due to its low toxicity.Allergic march is an environment-related immune disease which has been widely concerned in the world in recent years.Its Chinese translation is"persistent multiple type I hypersensitivity syndrome in children and adolescents",and its popular name is"persistent allergic symptoms in children".Although the underlying mechanism of DINP induced allergic march is still unclear,with the continuous deepening of research at home and abroad,it has been discovered that nuclear factor?B(NF-?B)is a ubiquitous and particularly important transcription factor in immune and inflammatory responses,and the impact of endoplasmic reticulum stress(ER stress)in allergic diseases has also been discovered.In this study,we established a mouse Allergic March model to study the effects of DINP exposure on Allergic March,and explored this by using the NF-?B signaling pathway antagonist PDTC and the ER stress pathway antagonist 4-PBA.Whether the impact is related to these two pathways,we hope that our research can provide a scientific basis for elucidating the molecular mechanism of DINP-induced Allergic March.In our experiment,we adopted the Allergic March model.Male BALB/c mice were used as test animals.They were randomly divided into 6 groups,including blank control group(normal saline),20 mg·kg^-1DINP group,OVA group,20 mg·kg^-1DINP+OVA group,PDTC antagonist group(20 mg·kg^-1DINP+OVA+PDTC)and4-PBA antagonist group(20 mg·kg^-1DINP+OVA+4-PBA),the period of exposure was 47 days.First,we measured airway hyperresponsiveness(AHR),and then performed lung histological analysis to study the toxicological effects of DINP.Next,the ELISA kit was used to detect T-Ig E,OVA-Ig E and OVA-Ig G1 in serum to evaluate the body's inflammatory factors,and lung tissue homogenate was used to determine Th17/Treg immune balance cytokines(IL-17,IL-10,IL-22.IL-6,TGF-?)and NF-?B levels.At the same time,observe the pathological changes of lung tissue and the expression of Foxp3,TAZ,IL-1?and TNF-?antibody and the expression of ER stress level markers(IRE1?,ATF6,CHOP)in lung tissue.The experimental results showed that compared with the normal saline group,the lung function,Th17 immune system hyperactive molecules,NF-?B/ER stress indicators were significantly increased in the OVA group,and the lung tissue pathological damage was aggravated.Compared with the OVA group,the lung function,Th17 immune system hyperactive molecules,and NF-?B/ER stress indicators in the 20 mg·kg^-1DINP+OVA group were significantly increased,and the lung tissue pathological damage was also aggravated.Compared with the 20 mg·kg^-1DINP+OVA group,the NF-?B pathway blocker PDTC group(20 mg·kg^-1DINP+OVA+PDTC)and the ER stress pathway blocker 4-PBA group(20 mg·kg^-1DINP+OVA+4-PBA),its various indicators have improved significantly.The experimental results showed that DINP of 20 mg·kg^-1can aggravate Allergic March in mice,and that NF-?B antagonist PDTC and ER stress antagonist 4-PBA can reduce the symptoms of Allergic March,and protect the lung tissue of mice.The protective effect indicates that the NF-?B/ER stress pathway may mediate the Allergic March caused by DINP.