关键词: 泻根醇酸, 脑缺血, PC12细胞, Ca²⁺, Bcl-2, Bax, p-CaMKII, p-CREB

Abstract: Calcium overload is considered as one of the mechanisms of cerebral ischemia.Ca²⁺ influx and Ca²⁺/calmodulin-dependent protein kinase II (CaMKII) and cAMP response element-binding protein (CREB)phosphorylation are considered to be involved in N-Methyl-D-aspartate (NMDA)-induced apoptosis process. In this study,we investigated the neuroprotective effects of bryonolic acid (BA) in the NMDA-induced rat’s adrenal pheochromocytoma cell line (PC12 cells) and the potential mechanism.NMDA induced cytotoxicity in PC12 cells was accompanied by cell viability decrease and lactate dehydrogenase (LDH) release,as well as Ca²⁺ influx,Bax up-regulation,p-CREB and Bcl-2 down-regulation.The results showed that pretreatment with BA significantly attenuated cells viability decrease and LDH release,as well as Ca²⁺ influx,Bax generation p-CREB and Bcl-2 protein increase.All these results indicated that BA protected PC12 cells against NMDA-induced apoptosis by inhibiting Ca²⁺ influx and regulating genes expression in Ca²⁺-CaMKII-CREB signal pathway.Therefore,the present study supported the notion that BA may be a promising neuroprotective agent for the treatment of cerebral ischemia disease.

Key words: bryonolic acid, PC12 cells, Ca²⁺, Bcl-2, Bax, p-CaMKII, p-CREB