Abstract: Objective To investigate the effect of mBDNF /Akt/CREB，proBDNF/ RhoA signaling imbalances in cognitive dysfunction caused by propofol in neonatal rats Methods Rats aged 7 days weighing 12-16g were randomly divided into 6 groups(n=12 each): group C were intraperitoneally injected with 0.9 % normal saline for 7 days, group P1 were injected normal saline for 6 days and propofol on the 7th day, group P2 were recived propofol for 7 days, group T，K and D were given propofol for 7 days and then respectively injected with TAT-Pep5，K252a and DMSO.Blood gas analysis and blood glucose were detected of 6 rats in each group. The other 6 rats in each group were subjected to Morris water maze to access learning and memory functions at age of 25 d and decapitated after the tests.The hippocampal tissues were taken to measure mBDNF /Akt/CREB，proBDNF/ RhoA by Western blot.Results Compared with group C, the escape latency was prolonged（P＜0.05）, space exploration time was shortened in group P1 and more obvious in P2. Compared with group D, the escape latency was prolonged, space exploration time was shortened in group K（P＜0.05）, the escape latency was shortened, space exploration time was prolonged in group T（P＜0.05）. The expression of mBDNF /Akt/ CREB in hippocampus were decreased in group P1 and gradually decreased in group P2（P＜0.05）. The proBDNF/ RhoA in hippocampus were increased in group P1 and gradually increased in group P2（P＜0.05）.Compared with group D, the Akt/ CREB were down-regulated in group K, the RhoA were reduced in group T（P＜0.05）. Conclusions Propofol anesthesia supressed the anti-apoptosis signal pathway of mBDNF /Akt/ CREB and enhanced the apoptosis signal pathway of proBDNF/RhoA in the hippocampal in neonatal rats, which may be the mechanism by which propofol leads to long-term cognitive dysfunction.

Key words: [key words] propofol, neonatal rats, BDNF, hippocampus