1.Downregulation of thioredoxin-interacting protein attenuates early brain injury after subarachnoid hem- orrhage of rats
Qing ZHAO ; Xudong CHE ; Guanping TAN ; Hongxia ZHANG ; Dengzhi JIANG ; Xiaochuan SUN ; Zhaohui HE
Chinese Journal of Nervous and Mental Diseases 2016;42(3):184-189
Objective To explore the possible mechanism by which thioredoxin-interacting protein (TXNIP) par?ticipated in early brain injury (EBI) of subarachnoid hemorrhage (SAH) via examination of the expression of TXNIP and its downstream apoptotic factors before and after intervention. Methods Subarachnoid Hemorrhage (SAH) was performed by endovascular perforation. Total 97 adult male SD rats were randomly divided into 6 groups:sham-operation (17), SAH (32), control siRNA (12), TXNIP siRNA (12), resveratrol control (12) and resveratrol injection (12). Western blot was used to examine the expression of TXNIP, p-ASK-1, Caspase-3 before and after intervention. Laser scanning confocal microscopy (LSCM) was used to detect the expression of TXNIP in neurons. The co-localization of TXNIP with apoptotic cells was examined by using fluorescent TUNEL. Mortality, behavior score and cerebral edema were also evaluated. Re?sults Mortality, behavior scores and brain edema were improved after TXNIP siRNA and resveratrol injection(P<0.05). LSCM showed that TXNIP was widely expressed in brain and mainly located in cytoplasm of neurons in SAH rats. Fluo?rescent TUNEL revealed the co-localization of TXNIP with apoptotic cells. The expression level of TXNIP was signifi?cantly higher in SAH group than in sham operation (P<0.05, n=3). The expression level of TXNIP gradually increased at 12h and still remained at high level at 72h (P<0.05). This increase was simultaneously accompanied by the increase in downstream apoptosis factors, p-ASK-1 and Caspase-3. Inhibition of TXNIP by siRNA or resveratrol significantly re?duced the expression of TXNIP, p-ASK-1 and Caspase-3 (P<0.05, n=3). Conclusion TXNIP gradually increases in ear?ly period after SAH and aggravates brain damage through activation of ASK-1 apoptosis signaling pathway, whereas inhi?bition of TXNIP may attenuate EBI through reduction of p-ASK-1 and Caspase-3 after SAH.