2022, Vol. 26 ›› Issue (23): 3714-3720

Salvianolic acid A effects on hippocampal protein expression in ischemic stroke rats: a tandem mass tag-based proteomic analysis

Xu Wenshan1, Jiang Pingli1, Liu Yulu1, Ding Yanyi1, Yu Yan1, Yang Minguang1, Liu Weilin2, 3, Chen Lidian3   

Abstract: BACKGROUND: It is unclear about the effect of salvianolic acid A on hippocampal protein expression after ischemic stroke and its mechanism.
OBJECTIVE: To observe the effect of salvianolic acid A on differential protein expression in the hippocampus of ischemic stroke rats, and to explore its possible neuroprotective mechanism.
METHODS: The modified Longa method was used to prepare a rat model of ischemic stroke. After modeling, the rats were randomly divided into normal saline group (n=6) and salvianolic acid A group (n=6). Salvianolic acid A (2 mg/kg) was injected through the tail vein after the cord plug was pulled out. The normal saline group was injected with the equal volume of normal saline. Neurological function of the rats was evaluated by the modified neurological deficit score. T2-weighted imaging was used to detect infarct volume. Open field test and Morris water maze test were used to observe the autonomous behavior, learning and memory ability of rats in each group. Tandem mass tag-based quantitative proteomics technique was used to analyze differential protein expression in the ischemic hippocampus of ischemic stroke model rats.
RESULTS AND CONCLUSION: Compared with the normal saline group, the modified neurological deficit score of rats was significantly decreased in the salvianolic acid A group. T2-weighted imaging results showed that the cerebral infarction volume in the salvianolic acid A group was significantly lower than that in the normal saline group. Results from the open field test showed that the rats in the salvianolic acid A group had better performance of autonomous activity and free exploration. Morris water maze test results showed that in the directional navigation experiment, the escape latency was significantly shortened and the number of platform crossings was significantly increased in the salvianolic acid A group compared with the normal saline group. Analysis of differentially expressed proteins in the ischemic hippocampus revealed that 50 differentially expressed proteins were up-regulated and 3 differentially expressed proteins were down-regulated between salvianolic acid A group and normal saline group. Gene ontology analysis showed that these differentially expressed proteins were mainly involved in several molecular functions such as binding and catalytic activity. Kyoto Encyclopedia of Genes and Genomes analysis showed that these differentially expressed proteins were mainly involved in several signaling pathways, such as complement and coagulation cascades, and Staphylococus aureus infection. All these findings indicate that salvianolic acid A may play a neuroprotective role in ischemic stroke rats by regulating differentially expressed proteins and complement and coagulation cascade signaling pathways in the ischemic hippocampus.   
Key words: salvianolic acid A, ischemic stroke, proteomics, tandem mass tag technology, neuroprotection, hippocampus, differentially expressed protein, bioinformatics