SRA

Hemorrhage stroke is a severe vascular disease of the brain with a high mortality rate in humans. Sodium tanshinone IIA sulfonate (STS) is a water-soluble derivative of tanshinone IIA, which is the main active ingredient of Salvia miltiorrhiza Bge (known as Danshen in Chinese) and has been approved as a commercial drug for treating cardiovascular disease by the China Food and Drug Administration. In our previous study, we established a HMG-COA inhibitor atorvastatin (Ator)-induced zebrafish model of cerebral hemorrhage and found that STS dramatically decreased both the hemorrhage rate and hemorrhage area, although the underlying mechanism was not fully elucidated. Therefore, in the present study, we conducted transcriptome analysis of the protective effect of STS against Ator-induced cerebral hemorrhage in zebrafish using RNA-Seq technology, and further clarify its underlying molecular mechanisms on HIF-1 and its regulators, i.e., the PI3K/Akt and MAPK signaling pathways were verified by real-time PCR analysis and specific pharmacological inhibitors. We are also able to show that hemoglobin, carbonic anhydrase, Na+/H+ exchanger and HIF-1 genes might be potential biomarkers of Ator-induced cerebral hemorrhage in zebrafish, as well as pharmacological targets of STS. This study also provided evidence of bio-markers involved in hemorrhage stroke and improved understanding of the effects of HMG-COA inhibition on vascular permeability and cerebral hemorrhage.