Effect of isoflurane or sevoflurane inhalation before and after gestation on the N-methyl-D-aspartate receptor expression in offspring rat hippocampus

Objective To evaluate the effect of isoflurane or sevoflurane inhalation before and after gestation on the N-methyl-D-aspartate (NMDA) receptor expression in offspring rat hippocampus.Methods Thirty female adult Sprague-Dawley rats,aged 3 months,weighing 250-300 g,were randomly assigned into 5 groups (n =6 each):control group (group C),exposure to isoflurane before gestation group (group BI),exposure to isoflurane during gestation period group (group PI),exposure to sevoflurane before gestation group (group BS),exposure to sevoflurane during gestation period group (group PS).The rats inhaled 1.6％ isoflurane for 6 h at 1 day before gestation in group BI.The rats inhaled 1.6％ isoflurane for 6 h at 6,10,14 and 18 day gestation in group PI.The rats were exposed to 2.4％ sevoflurane for 6 h before gestation in group BS.The rats were exposed to 2.4％ sevoflurane for 6 h at 6,10,14 and 18 day gestation in group PS.Twelve offspring rats from pregnant rats in each group were chosen on the day of birth (T1),and 7th,14th and 28th days after birth (T2-4) and sacrificed,and the hippocampi were then isolated for determination of the expression NMDA receptor (NR1,NR2A and NR2B).Results Compared with group C,no significant change was found in NMDA receptor expression in off spring rat hippocampus in groups BI and BS (P ＞ 0.05),and the expression of NR1 and NR2A protein and mRNA was significantly up-regulated,and the expression of NR2B protein and mRNA was down-regulated at T1-3 (P ＜0.05),and no significant change was found in NMDA receptor expression at T4 in groups PI and PS (P ＞ 0.05).Compared with group PI,the expression of NRI and NR2A protein and mRNA was significantly up-regulated,and the expression of NR2B protein and mRNA was down-regulated at T1 3 (P ＜ 0.05 or 0.01),and no significant change was found in N MDA receptor expression at T4 in group PS (P ＞ 0.05).Conclusion Isoflurane or sevoflurane inhalation before gestation does not affect the NMDA receptor expression in offspring rat hippocampus,while isoflurane or sevoflurane inhalation after gestation can induce abnormal expression of the NMDA receptor in offspring rat hippocampus,which may result in apoptosis in hippocampal cells and abnormality in the development of nervous system and cognitive function. Key words: Isoflurane;  Anesthetics,inhalation; Pregnancy, animal;  Receptors, N-methyl-D-aspartate; Hippocampus