ABSTRACT
OBJECTIVE：To investig ate the effects of tenuifolin （TEN）on brain mitochondrial autophagy in Aizheimer ’s disease（AD）model mice. METHODS ：Totally 50 male APP/PS1 double transgenic mice were randomly divided into model group，TEN medium-dose+ 3-MA group [TEN 40 mg/（kg·d）+autophagy inhibitor 3-MA 30 mg/（kg·d）] and TEN low-dose ， medium-dose and high-dose groups [ 20，40，80 mg/（kg·d）]，with 10 mice in each group. In addition ，10 wild-type homologous mice were included in normal control group. Administration groups were intragastrically given corresponding drug solution ；normal control group and model group were intragastrically given 0.3％ sodium carboxymethyl cellulose solution ，once a day ，0.01 mL/g， for consecutive 3 months. After last administration ，positive expression [measured by integrated optical density （IOD）] of microtubule associated protein 1 light chain 3（LC3）in neuron was detected ；mRNA expressions of LC3，ubiquitin-binding protein p62，Cathepsin D ，Rab7，phosphatase and tensin homolog deleted on chromosome ten gene-induced putative kinase 1（PINK1） and E 3 ligase（Parkin）as well as protein expressions of LC 3，p62，PINK1 and Parkin were detected in brain mitochondria. RESULTS：Compared with normal control group ，IOD value of LC 3 in neuron as well as mRNA and protein expressions of LC 3， p62，PINK1 and Parkin in brain mitochondria were all increased significantly in model group （P＜0.05 or P＜0.01），while mRNA expressions of Cathepsin D and Rab 7 were decreased significantly （P＜0.05 or P＜0.01）. Compared wit h model group ，IOD values of LC 3（except for TEN low-dose and medium-dose groups ） in neuron ，mRNA expressions of LC 3，Cathepsin D ，Rab7， PINK1（except for TEN low-dose group ）and Parkin （except for TEN low-dose group ） in brain mitochondria as well as protein expressions of LC 3 （except for TEN medium-dose group），PINK1（except fo r TEN high-dose group decreased significantly）and Parkin （except for TEN low-dose group decreased significantly ）were increased significantly in TEN low-dose ， medium-dose and high-dose groups （P＜0.05 or P＜0.01）；mRNA（except for TEN low-dose group ）and protein expressions of p62 were decreased significantly （P＜0.05 or P＜0.01）. Compared with TEN medium-dose group ，the changes of above indexes were inhibited significantly in TEN medium-dose + 3-MA group （P＜0.05 or P＜0.01）. CONCLUSIONS ：TEN can induce mitophagy in brain tissue of AD model mice by activating PINK 1/Parkin signaling pathway and improve lysosome function.