OBJECTIVE To probe into the protective effect of different dose of secoisolariciresinol diglucoside(SDG)on brain of offspring of mice anainst oxidative damage and inflammatory reaction induced by maternal exposure to trans fatty acids(TFA)during gestation,and observe the the changes of regulating Nrf2/Keap1 pathway in the course.METHODS 30 healthy female mice(C57BL/6)were divided into 5 groups randomly,they are respectively control group,TFA-exposed group,and three SDG-intervention groups(low-(TFA+LSDG),medium-(TFA+MSDG)and high-(TFA+HSDG)).The pregnancy mice of control group and TFA group were treated with distilled water and 60 mg/kg·d TFA by gavage,in the same time,the mice of three SDG-intervention groups were treated with 60 mg/kg·d TFA by gavage and fed with feed included SDG(10,20 and 30 mg/kg).The treatment to pregnancy mice continued to birth of offspring.After 21 days of lactation,the offspring were killed under anesthesia and the experiment was ended.The coefficient of brain was calculated.The levels of superoxide dismutase(SOD),glutathione peroxidase(GSH-Px),malondialdehyde(MDA),tumor necrosis factor-α(TNF-α),interferon-γ(IFN-γ)and amyloid-β(Aβ)of brain were detected.RT-PCR and Western Blot was used to detected gene expression and protein levels of nuclear factor erythroid-2 related factor 2(Nrf2),kelch-like ECH-associated protein 1(Keap1),quinone oxidoreductase 1(NQO1)and hemeoxygenase-1(HO-1).RESULTS Compared with control group,the brain coefficient and Aβ1-40 of offspring of TFA-group had no significant changes(P＞0.05),the activity of SOD and GSH-Px reduced,the content of MDA,IFN-γ,TNF-α and Aβ1-42 increased,the level of mRNA and protein expression of Nrf2,NQO1 and HO-1 decreased and the level of mRNA and protein expression of Keap1 increase because of the exposion to TFA during gestation and all the differences were statistically significant(P＜0.05).Compared with TFA-group,the brain coefficient,Aβ1-40 and the level of NQO1 mRNA of offspring of three SDG-intervention groups had no significant changes(P＞0.05),the activity of SOD(the middle and high dose SDG intervention groups)and GSH-Px(three SDG-intervention groups)increased,the content of MDA(the middle and high dose SDG intervention groups),IFN-γ(the middle and high dose SDG intervention groups),TNF-α (three SDG-intervention groups)and Aβ 1-42(the middle and high dose SDG intervention groups)decreased,the mRNA expression of Nrf2 and HO-1(the middle and high dose SDG intervention groups)was up-regulated,the mRNA expression of Keap1(the middle and high dose SDG intervention group)decreased,proteic expression of Nrf2,NQO1 and HO-1 of three SDG-intervention groups increase and the level of protein of Keap1 decreased because of the intervention of SDG during gestation(P＜0.05).CONCLUSION These result suggest that maternal TFA exposure during gestation can result in oxidative stress and inflammation to brain of offspring in a way.SDG can protect brain of mice of offspring from TFA-induced oxidative injury by up-regulating the expression of mRNA and protein of Nrf2,down-regulating the expression of Keap1,accelerating expression of protein of NQO1 and HO-1 which are antioxidant protein lying downstream of pathway of Nrf2/Keap1.
trans fatty acidssecoisolariciresinol diglucosideoxidative damageinflammationNrf2/Keap1 pathway
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