The crosstalk signals of Sodium Tanshinone ⅡA Sulfonate in rats with cerebral ischemic stroke: Insights from proteomics

Abstract

BackgroundStroke could cause long-term disability, even mortality around the world. Recently, Sodium tanshinone IIA sulfonate (STS), identified from Salvia miltiorrhiza Bunge and was found to have unique efficiency in clinical practice as a potential therapeutic agent for ischemic cerebral infarction. However, systematic investigation about the biological mechanism is still lacking. Herein, we utilized high-throughput proteomics approach to identify the underlying targets for the treatment of STS in stroke. MethodsWe investigated the effect of STS on stroke outcomes on rat model of the Middle Cerebral Artery Occlusion and Reperfusion (MCAO/R), assessing by Z-Longa score, infarct volume and HE staining. Pharmacoproteomic profiling of ischemic penumbra in cortical (IPC) was performed using DIA-based label-free liquid chromatography-tandem mass spectrometry (LC-MS/MS) technique. Bioinformatics analysis was processed for further investigation. The expression of core proteins was semi-quantified by DIA, and the major protein correlating with stroke was examined using parallel reaction monitoring (PRM). ResultsRats in the MCAO/R group showed neurological function deterioration, which was improved by STS. There were 423 differentially expressed proteins (DEPs) in IPC being detected and quantified in both the sham group and the MCAO/R group. Meanwhile, 285 proteins were significantly changed in the STS treated group, compared to the MCAO/R model. Protein-protein interaction (PPI) network, pathway and biological function enrichment were processed for the DEPs across each two groups, the results of which were integrated for analysis. Alb, mTOR, Dync1h1, Stxbp1, Cltc, and Sptan1 were contained as the core proteins. Altered molecules were discovered to be enriched in 18 signal pathways such as phosphatidylinositol signaling system, PI3K/AKT signal pathway and HIF-1 signal pathway. The results also showed the correlation with sleep disturbances and depression post-stroke. ConclusionsWe concluded that STS could prevent penumbra from progressively ongoing damage and improve neurological deficits in MCAO/R model rats. The intersected pathways and protein networks predicted by proteomics might provide much more detailed information for the therapeutic mechanisms of STS in the treatment of CIS.