Abstract: Objective To investigate the regulation and mechanism of Herkinorin preconditioning on NOD-like receptor protein 3 (NLRP3) in brain tissue of transient middle cerebral artery occlusion (tMCAO) rats. Methods Rats were randomly divided into sham operation group (sham), model group (tMCAO) and Herkinorin group (Herkinorin). Before modeling, rats in Herkinorin group were intraperitoneally given Herkinorin (10 mg/kg) once a day for a week. The rats were evaluated by neurologic score, TTC staining, TUNEL staining 24 h after reperfusion. The expression levels of IκBα, p65, p-p65, pro-IL-1β, IL-1β, pro-caspase1, caspase1 p20 and NLRP3 were detected by Western blot. The binding level of IκBα to β-arrestin2 was detected by co-immunoprecipitation (Co-IP). Results Compared with sham group, rats in tMCAO group had higher behavioral score (P＜0.01), increased cerebral infarction percentage and increased cerebral edema rate (P＜0.01). The level of cell apoptosis was increased in ischemic penumbra (P＜0.01). The expression levels of IκBα and p65 were decreased (P＜0.01) and the expression levels of p-p65, IL-1β, caspase1 p20 and NLRP3 were increased in ischemic penumbra (P＜0.01). The binding level of IκBα to β-arrestin2 was decreased in ischemic penumbra (P＜0.01). Compared with tMCAO group, rats in Herkinorin group had lower behavioral score (P＜0.01), lower cerebral infarction percentage and lower cerebral edema rate (P＜0.01). The level of cell apoptosis was decreased in ischemic penumbra(P＜0.01). The expression of IκBα and p65 was increased (P＜0.01) and the expression of p-p65, IL-1β, caspase1 p20 and NLRP3 was decreased in ischemic penumbra (P＜0.01). The binding of IκBα to β-arrestin2 was increased in ischemic penumbra (P＜0.01). Conclusions Herkinorin may negatively regulate NF-κB/NLRP3 pathway to alleviate cerebral ischemia-reperfusion injury of tMCAO rats.

Key words: Herkinorin, transient middle cerebral artery occlusion, NOD-like receptor protein 3, NF-κB, β-arrestin2