Qiangji decoction activates AMPKα/SIRT1/PGC-1α signaling pathway to attenuate cognitive impairment and mitochondrial dysfunction induced by D-galactose
AIM:To investigate the mechanism by which Qiangji decoction attenuates cognitive impairment and mitochondrial dysfunction induced by D-galactose.METHODS:Eighty C57BL/6 mice were randomly divided into control group,model group,metformin group,and Qiangji decoction group.D-galactose(100 mg·kg-1·d-1)was injected into the neck of mice,excluding those in control group,for 8 weeks to establish an aging-related cognitive impairment model.The mice in Qiangji decoction group received Qiangji decoction(24.96 g·kg-1·d-1),those in metformin group re-ceived metformin(0.2 g·kg-1·d-1),and those in other groups were administered an equal volume of normal saline for 4 weeks(20 mL·kg-1·d-1).Morris water maze and novel object recognition tests were used to assess mouse learning and memory.Fluoro-Jade B(FJB)staining was used to observe damaged neurons in the hippocampus.Transmission electron microscopy was employed to observe the ultrastructure of mitochondria in hippocampal nerve cells.The levels of reactive oxygen species(ROS)in hippocampal nerve cells were detected using a kit.Mitochondrial membrane potential was mea-sured by JC-1 staining.Kits were used to measure the levels of mitochondrial ATP,and mitochondrial respiratory chain complexes I,III and IV in the hippocampus.The protein levels of AMP-activated protein kinase α(AMPKα),phosphory-lated AMPKα at Thr172(p-AMPKα-Thr172),silent information regulator 1(SIRT1),peroxisome proliferator-activated receptor γ coactivator-1α(PGC-1α),nuclear respiratory factor 1(NRF1),NRF2 and mitochondrial transcription factor A(TFAM)in the hippocampus were detected by Western blot.RESULTS:Morris water maze and novel object recogni-tion tests showed that compared with model group,the escape latency of the mice in metformin and Qiangji decoction groups significantly decreased(P<0.05 or P<0.01),while the number of platform crossings,time spent in the target quadrant,and novel recognition index significantly increased(P<0.05 or P<0.01).The results of FJB staining indicated that compared with model group,the numbers of FJB-positive neurons in mouse hippocampal CA1 and CA3 regions signifi-cantly decreased in metformin and Qiangji decoction groups(P<0.05 or P<0.01).Transmission electron microscopy re-vealed that compared with model group,damaged mitochondria in mouse hippocampal neurons were reduced in metformin and Qiangji decoction groups,with increased mitochondrial length and area(P<0.05 or P<0.01).Compared with model group,ROS levels in mouse hippocampal neurons significantly decreased in metformin and Qiangji decoction groups(P<0.05 or P<0.01).The results of JC-1 staining demonstrated that compared with model group,mitochondrial membrane potential significantly increased in metformin and Qiangji decoction groups(P<0.05 or P<0.01).Compared with model group,the levels of mitochondrial ATP,and complexes I,III and IV in the hippocampus significantly increased in metfor-min and Qiangji decoction groups(P<0.05 or P<0.01).Western blot analysis showed that compared with model group,the protein levels of p-AMPKα-Thr172,SIRT1,PGC-1α,NRF1,NRF2 and TFAM in mouse hippocampal tissues signifi-cantly increased in metformin and Qiangji decoction groups(P<0.05 or P<0.01).CONCLUSION:Qiangji decoction al-leviates cognitive impairment,neuronal damage and mitochondrial dysfunction induced by D-galactose through activation of the AMPKα/SIRT1/PGC-1α signaling pathway.
万方数据
维普
