Study On The Endoplasmic Eticulum Stress Mediated Thioredoxin-interacting Protein Expression In Pathological Procession Of Early Brain Injury After Experiment Subarachnoid Hemorrhage Of Rats

Objective: As an important pro-oxidant protein in vivo, Thioredoxin-interacting protein(TXNIP) had been identified could induce apoptosis and inflammatation under various stress. Our previous study had confirmed Endoplasmic eticulum stress(ER stress) participated in pathological procession of early brain injury(EBI) after subarachnoid hemorrhage(SAH). Intriguingly, recently some elegant researches found ER stress significantly induced TXNIP expression at transcription and post-transcription levels. So this experiment applied appropriate interventions on TXNIP and ER stress, tried to authenticate the relationship between ER stress-TXNIP signaling pathway and EBI.Methods: SAH models were performed by endovascular perforation, TXNIP expression in early 72 hours and its downstream factors were measured. TXNIP siRNA and its inhibitor-Resveratrol were applied to downregulate TXNIP generation. The special inhibitors-GSK2656157, STF-083010 of ER stress sensors PERK, IRE1α were utilized. Immunofluorescence and TUNEL fluorescent double-labeling detected the location of TXNIP in cerebral and apoptotic cells. TXNIP and its upstream and downstream factors were measured by Western blot, and TUNEL positive cells were counted. Meanwhile, mortality, SAH grade, neurological deficits, brain water content and blood-brain barrier(BBB) permeability had been evaluated.Results: The expression of TXNIP was significantly elevated in early period after SAH, along with its downstream factors. Fluorescence showed that TXNIP expressed in neurons, microglia and astrocytes, colocalized with TUNEL positive cells. Downregulation of TXNIP could significantly reduce downstream apoptosis factors generation and inflammatory cytokines releasing. Suppressing TXNIP expression could attenuate the prognosis of SAH rats.Conclusion: As the destiny executor, Endoplasmic eticulum participates in variety death regulation. Here, we confirmed that TXNIP induced by ER stress could aggravate EBI after SAH through promoting apoptosis and inflammatory amplification. Inhibition of TXNIP may be a new effective strategy for treatment of SAH.