Objective To investigate the effect of ketamine anesthesia in early pregnancy on expression of hippyragranin (HGN) mRNA in hippocampus in offsprings of rats.Methods One hundred and twenty pregnant Sprague-Dawley rats at 5-7 days of gestation,aged 7 weeks,weighing 270-300 g,were randomly divided into 4 groups (n =30 each):2 h anesthesia with ketamine group (group K1),4 h anesthesia with ketamine group (group K2),8 h anesthesia with ketamine group (group K3) and control group (group C).Ketamine 20 mg/kg was injected via the caudal vein,followed by continuous intravenous infusion at 130 mg· kg-1 · h-1 after loss of righting reflex,and the infusion lasted for 2,4 and 8 h in groups K1-K3,respectively.The equal volume of normal saline was given instead of ketamine in group C.The learning ability and memory of the offsprings were tested by Morris water maze test on postnatal day 30.The offsprings were sacrificed on 2nd day after the end of Morris water maze test,their brains were removed and hippocampi were isolated for determination of the expression of HGN mRNA by RT-PCR.Results Compared with group C,the escape latency was significantly prolonged,the frequency of crossing the original platform was decreased,the time of staying at the original platform quadrant was shortened,and the expression of HGN mRNA was up-regulated in groups K1-K3 (P ＜ 0.05).There was no significant difference in the escape latency,frequency of crossing the original platform and time of staying at the original platform quadrant among groups K1-K3 (P ＞ 0.05).The expression of HGN mRNA was significantly higher in group K3 that in group K1 (P ＜ 0.05).There was no significant difference in the expression of HGN mRNA between group K2 and group K3 (P ＞ 0.05).Conclusion The mechanism by which ketamine anesthesia in the early pregnancy induces impairment of learning ability and memory of the offsprings is related to up-regulation of HGN mRNA expression in hippocampus in offsprings of rats.