Exploration of the Effect and Mechanism of Erzhi Pills on Synaptic Damage of Mice Based on miR-124/SIRT1 Signaling Pathway
Objective To investigate the effect and mechanism of Erzhi Pills on synaptic damage of mice based on miR-124/SIRT1 signaling pathway. Methods C57BL/6J mice were randomly divided into blank group,model group,negative viral control group,positive drug group(resveratrol 50 mg·kg-1·d-1),and Erzhi Pills group(3.5 g·kg-1·d-1),with 10 mice in each group. A miR-124-UP mouse model was replicated using intraventricular injection of adenovirus. The corresponding drug was administered by gavage after modeling,once a day for 42 days. Morris water maze was used to detect the learning and memory ability of the mice. Pathological changes in hippocampal tissue were observed using HE and Nissl staining. The kits were used to detect the serum levels of malondialdehyde (MDA) and glutathione peroxidase(GSH-PX). Western Blot was used to determine the protein expression of SIRT1,BDNF,CREB,SYN and PSD95 in hippocampal tissues,and qPCR was used to determine the mRNA expression of miR-124,SIRT1,BDNF,CREB,SYN and PSD95 in hippocampal tissues. Results Compared with the blank group,escape latency at the 5th day of the model group was significantly prolonged (P<0.01),while the number of crossing platforms was significantly reduced (P<0.001). Nerve cells in the CA3 region of the hippocampus were markedly reduced,with atrophied cells and densely stained nuclei. Serum MDA content was markedly up-regulated (P<0.001),and GSH-PX enzyme activity appeared to be significantly down-regulated(P<0.001). The protein and mRNA expression of SIRT1,BDNF,CREB,SYN,and PSD95 in hippocampal tissue appeared significantly down-regulated(P<0.05,P<0.01,P<0.001),but the mRNA expression of miR-124 in hippocampal tissue was significantly up-regulated (P<0.01). Compared with the model group,escape latency at the 5th day of positive drug group and Erzhi Pills group was obviously shortened(P<0.01)and the number of crossing platforms was significantly increased (P<0.01,P<0.001). Nerve cells in the CA3 region of the hippocampus was increased,the cell morphology tended to be normal,and the number of atrophic cells was decreased. The serum MDA content was significantly down-regulated(P<0.001),and the GSH-PX enzyme activity was significantly up-regulated (P<0.01,P<0.001). The protein expression of SIRT1,BDNF,CREB,SYN,and PSD95 in hippocampal tissue was significantly up-regulated (P<0.01,P<0.001). The mRNA expression of miR-124 in hippocampal tissue was significantly down-regulated (P<0.01). The mRNA expression of SIRT1,BDNF,CREB,SYN and PSD95 in hippocampal tissue was significantly up-regulated (P<0.05,P<0.01,P<0.001). The protein expression of SYN in hippocampal tissue of Erzhi Pills group was significantly increased(P<0.001). Conclusion Erzhi Pills could improve the learning and memory ability,enhance anti-oxidative stress and ameliorate neuronal cell damage in miR-124-UP mice,which may be related to the regulation neuronal plasticity through the miR-124/SIRT1 signaling pathway.
万方数据
维普
