Résumé
ObjectiveTo investigate the effect of linalool against acute liver injury induced by aflatoxin B1（AFB1） in rats and explore its protective mechanism. MethodTwenty male SPF SD rats were randomly divided into three groups： Control （n=6）， AFB1 （n=7）， and linalool （n=7） groups. Linalool solution （200 mg·kg-1） was administered preventatively for 14 days， while the control and AFB1 groups intragastrically received an equivalent volume of double distilled water. After preventative administration of linalool， AFB1 solution （1 mg·kg-1， dissolved in saline） was intraperitoneally injected for two consecutive days to induce acute liver injury in rats. Samples were collected and processed 14 days after model establishment. Pathological changes in liver tissue of rats were observed using Hematoxylin-eosin（HE） staining and Masson staining. Biochemical detection was performed to measure the levels of alanine transaminase（ALT）， aspartate transaminase（AST）， γ-glutamyl transferase（GGT）， lactate dehydrogenase（LDH）， alkaline phosphatase（ALP）， total bilirubin（TBil）， direct bilirubin（DBil）， indirect bilirubin（IBil）， malondialdehyde（MDA）， superoxidedismutase（SOD）， catalase（CAT） ， glutathione（GSH）， Fe3+， and Fe2+ in the liver tissue. Western blot was adopted to assess protein expression levels of nuclear factor-erythroid 2-related factor 2（Nrf2） and heme oxygenase-1（HO-1）. Molecular docking was performed to verify the binding between linalool and key proteins of the Nrf2/HO-1 signaling pathway. Molecular dynamics techniques were used to confirm the stability and affinity of linalool binding with key proteins of the Nrf2/HO-1 signaling pathway. ResultPathological results showed that compared to that in the AFB1 group， the liver structure in the linalool group tended to be normal， with a significant decrease in blue collagen fibers. The linalool group exhibited significantly reduced levels of ALT， AST， GGT， LDH， ALP， TBil， DBil， and IBil （P<0.01）， Fe3+ and Fe2+ content， and oxidative stress marker MDA （P<0.01）. The levels of antioxidants SOD， CAT， and GSH significantly increased （P<0.01）. Molecular docking showed a molecular docking energy between linalool and Nrf2 and HO-1 targets of -5.495 6 and -5.199 4 kcal·mol-1（1 cal≈4.186 J）， respectively. Molecular dynamics results indicated strong affinity in the binding of linalool with Nrf2 and HO-1. Western blot revealed a significant increase in Nrf2 protein expression （P<0.05） and a decrease in HO-1 protein expression （P<0.01） in the linalool group. ConclusionLinalool may protect against AFB1-induced acute liver injury by modulating the Nrf2/HO-1 ferroptosis signaling pathway to inhibit liver cell ferroptosis and regulate hepatic oxidative stress levels.
Résumé
Objective@#To explore the role of parenting style in the association of maternal adverse childhood experiences (ACEs) and emotional behavior problems (EBPs) in preschool children, so as to provide a reference for the prevention and control of EBPs in children.@*Methods@#A total of 6 111 children aged 3-6 years old from 36 kindergartens in 3 areas of Anhui Province in June 2021, follow up data were collected in December 2021. Maternal ACEs, mother child relationship and children EBPs were respectively assessed using the Adverse Childhood Experiences International Questionnaire(ACEs-IQ), Parental Rearing Style Scale and the difficulty score factor in the Chinese Strength and Difficulty Questionnaire(SDQ). The Bootstrap was used to examine the mediation effect of maternal parenting styles.@*Results@#Maternal ACEs were positively associated with child SDQ difficulty scores( r = 0.28, P <0.01). Negative parenting (indulgent, permissive, authoritarian and inconsistent) were positively correlated with maternal ACEs scores( r =0.28, 0.30, 0.21, 0.31) and child SDQ difficulty scores( r =0.25, 0.20, 0.20, 0.28)( P <0.01). Positive parenting (democracy) was negatively correlated with maternal ACEs and SDQ difficulty scores( r =-0.09, -0.29, P <0.01). After adjusting for confounding factors, the results of the mediation effect test of Bootstraping procedure showed that maternal parenting styles (indulgent, democracy, permissive, authoritarian and inconsistent) played a mediation role in maternal ACEs and EBPs of preschool children, and the mediation effects were respectively 19.13%, 7.34%, 24.88%, 12.05% and 26.83%.@*Conclusion@#Parenting styles play a mediating role in the association of maternal ACEs and EBPs in preschool children, and improving mothers negative parenting styles is of great significance to reduce EBPs in the offspring of maternal ACEs.