基于敌百虫促进DNMT3A表达致空间学习记忆能力下降及海马神经元细胞凋亡OA

Objective:To explore the effects of continuous exposure to trichlorfon on spatial learning and memory ability and neuronal cells in rats,and to provide a reference for the study of the mechanism of trichlorfon neurotoxicity.Methods:Based on previous studies,SD rats were gavaged with PBS buffer or 10 mg/kg of trichlorfon for 30 days,and the learning and memory abili-ty of the rats was evaluated by water maze test,the morphology of hippocampal neurons was observed by H&E staining,5-methyl-cytosine(5-mc)was detected by immunohistochemistry staining,cell apoptosis was observed by TUNEL staining,and the ex-pression of DNMT3A and apoptosis-related genes was detected by Western blot.HT-22 mouse hippocampal neurons were treated with 0,160,200,240 μmol/L for 48 hours,and the expression of DNMT3A and apoptosis-related genes was detected by Western blot,and cell apoptosis was detected by flow cytometry.After HT-22 cells knocked down DNMT3A,200 μmol/L trichlorfon was intervened for 48 hours,and the expression of DNMT3A and apoptosis-related genes was detected by Western blot.Results:After the intervention of trichlorfon,the results of water maze test showed that the learning and memory ability of rats decreased(P<0.05),H&E staining results showed no significant changes in hippocampal tissue morphology,and immunohistochemical staining showed that the level of 5-mc in hippocampal tissue increased(P<0.05);Western blot results showed that after trichlor-fon treatment,the expression of DNMT3A increased(P<0.05),the expression of apoptosis-related genes changed(P<0.05),and flow cytometry showed that the apoptosis rate increased(P<0.05),but knocking down DNMT3A could partially reverse the apoptosis induced by trichlorfon(P<0.05).Conclusions:Continuous exposure to trichlorfon led to a decline in cognitive function in rats,which may be related to the increased expression of DNMT3A and the apoptosis caused by increased DNA methylation levels.