Early proapoptotic role of thioredoxin-interacting protein after subarachnoid hemorrhage: an experimental study

Abstract

Objectives To detect the expression of thioredoxin-interacting protein (TXNIP) and its related apoptosis factors after subarachnoid hemorrhage (SAH) and to investigate the role and its mechanism of TXNIP in early brain injury after SAH. Methods A rat SAH model was induced by intravascular puncture. A sham operation group, a SAH group, a resveratrol intervention control group, and a resveratrol intervention group were set up. Immunofluorescence staining was used to observe the expression of neuronal TXNIP. The fluorescent TUNEL assay was used to detect cell apoptosis and TXNIP colocalization. Western blot was used to detect the expression changes of TXNIP, p-ASK-1, Caspase-3, Bax, and Bcl-2 at each time point before and after the intervention within 72 h after SAH. TUNEL assay was used to detect the cortical and hippocampal cell apoptosis before and after intervention, and the changes of behavior and brain edema were assessed before and after intervention at the same time. Results The results of immunofluorescence staining showed that TXNIP was mainly expressed in neuronal cytoplasm. Fluorescent TUNEL assay found that there was colocalization between TXNIP and subcortical apoptotic cells. Compared with the sham operation group, TXNIP expression increased gradually at 12 h after SAH. The expression at each time point early after hemorrhage was higher than that of the sham operation group (all P<0.05). At the same time, the expression levels of p-ASK-1, Caspase-3, and Bax were increased, and the expression of Bcl-2 was decreased. There were significant differences (all P<0.05). After resveratrol intervention, TXNIP and p-ASK-1, Caspase-3, and Bax were downregulated (all P<0.05). The results of TUNEL assay showed that the apoptotic cells decreased after intervention (P<0.05). Behavioral score and cerebral edema were also improved (all P<0.05). Conclusions Early TXNIP expression began to increase after SAH. TXNIP might aggravate early brain damage after SAH through its proapoptotic effect, and resveratrol could improve brain cell death and the prognosis in rats by inhibiting TXNIP. The downregulation of the TXNIP expression might become a new treatment measure at early stage after SAH. Key words: Subarachnoid hemorrhage; Thioredoxin-interacting protein; Early brain injury; Apoptosis; Rats