Effects of Zuogui Pills on the learning ability of offspring of prenatal stress in pregnant rats through the IL-6/JAK2/STAT3 signaling pathway
Objective:To explore the mechanism of Zuogui Pills in protecting learning ability of offspring under prenatal stress(PS)based on IL-6/JAK2/STAT3 signaling pathway.Methods:A total of 50 pregnant rats were randomly divided into control,model,anti-IL-6 and Zuogui Pills low and high dose groups.PS pregnant rat models were replicated by chronic unpredictable mild stress(CUMS)during the whole pregnancy in all groups except the blank group.From the 12th day of pregnancy,the intragastric doses of Zuogui Pills in the low-dose group and high-dose group were 0.39 and 0.78 mg/kg,respectively.The normal group and model group were intragastrically administered with 10 mL/kg normal saline.The dams in the anti-IL-6 group were intraperitoneally injected with IL-6 antibody 10 pg/day until the rats give birth.The PS model was evaluated through the sugar water preference experiment and the open field test.The learning and memory abilities of offspring assessed by Morris water maze.The serum interleukin-6(IL-6)contents of the dams and the litter by enzyme-linked immunosorbent assay(ELISA).The number of immature neurons in the hippocampus of the offspring was assessed by Nissl staining.Terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL)method was used to detect the apoptosis level of hippocampal neurons by fluorescence,the expression levels of IL-6,tyrosine protein kinase 2(JAK2)and transcriptional activator 3(STAT3)proteins with their phosphorylated proteins in hippocampus of the rats were detected by Western Blot.Results:Compared with the blank group,the learning ability of the offspring in the model group decreased(P＜0.01);the number of mature hippocampal neurons decreased and apoptosis increased(P＜0.01);the serum IL-6 content of the dams and offspring increased(P＜0.01);the expression of IL-6 protein and JAK2 and STAT3 phosphorylated proteins in the hippocampus of offspring mice increased(P＜0.01).Compared with the model group,each dose group of Zuogui Pills and the anti-IL-6 group improved learning ability to varying degrees(P＜0.01);the number of mature hippocampal neurons in offspring increased and apoptosis decreased(P＜0.01,P＜0.05);the expression of IL-6 in the serum of dams and offspring,as well as IL-6 protein and JAK2 and STAT3 phosphorylated proteins in the brain hippocampus of offspring were down-regulated(P＜0.01).Conclusion:The mechanism of PS mothers affecting their offspring learning ability may be neuronal apoptosis mediated by IL-6/JAK 2/STAT3.
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