Effect of phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin signaling pathway inhibition on autophagy related protein expressions in CA1 area of hippocampus of vascular dementia rats

Objective To investigate the effect of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway on expressions of autophagy related proteins in CA1 area of hippocampus in vascular dementia (VD) rat models. Methods One hundred and eight healthy male SD rats were randomly divided into sham-operated group, VD group, PI3K inhibitor LY294002 group (LY294002 group) and mTOR inhibitor rapamycin group (rapamycin group, n=27); the VD models in the later three groups were prepared by modified Pulsineli’s four-vessel occlusion; lateral ventricles in the later two groups were injected 10 mmol/L LY294002 solution 10 μL or 8 ng/μL rapamycin 4 μL before preparing of VD models. One, 2, 4 and 8 weeks after the success of model preparation, the autophagy associated protein Beclin1 expression and microtubule-associated protein light chain (LC)3II/LC3I ratio in CA1 area of the hippocampus were detected by Western blotting. The expression of LC3 was detected in CA1 area of the hippocampus by fluorescence microscope 4 weeks after the success of model preparation. Results (1) As compared with those in the sham-operated group, the Beclin1 expression and LC3II/LC3I ratio in VD group were significantly increased at all observation time points (P<0.05); As compared with those in the VD group, the Beclin1 expression and LC3II/LC3I ratio in the LY294002 group and rapamycin group were significantly increased at all observation time points (P<0.05). (2) At 4 weeks after the success of model preparation, immunofluorescence results showed that LC3 in the cytoplasm of neurons was scattered with low expression in the sham-operated group, the LC3 expression was increased in the VD group, and that in the LY294002 group and rapamycin group was obviously increased. Conclusion Inhibition of PI3K/Akt/mTOR signaling pathway can promote the expressions of autophagy related protein Beclin1 and LC3 in CA1 area of the hippocampus of vascular dementia rats, and neuronal autophagy is significantly enhanced. Key words: Vascular dementia; Phosphatidylinositol 3-kinase; Protein kinase B; Mammalian target of rapamycin; Autophagy; Beclin1; Microtubule-associated protein light chain 3