The effects of JNK pathway on isoflurane induced neuronal apoptosis in the hippocampi of neonatal rats / 中华行为医学与脑科学杂志

ABSTRACT

Objective To investigate the effects of the c-Jun N-terminal kinase (JNK)pathway on isoflurane induced neuronal apoptosis and the proteins expression of phospho-JNK,Bcl-2 and Bax in the hippocampi of neonatal rats.Methods Forty-eight neonatal rats at postnatal day 7 (P7) were randomly assigned into 4 groupsDMSO control group (group D),SP600125 control group (group SP30),isoflurane + DMSO group (group Iso +D),isoflurane + SP600125 group (group Iso + SP30).Rats were exposed to air (control group) or 1.1％ isoflurane (isoflurane group) for 4 h.The JNK inhibitor SP600125 at 30 μg or 12％ DMSO 5 μl was intraventricularly administered 20 min before the exposure.The brains of some rats in each group were perfused and embedded by paraffin 6 h after the exposure.Neuronal apoptosis in the hippocampi CA1 area was detected by TUNEL (n =6).The fresh hippocampi of other rats in each group were dissected 6 h after the exposure and the proteins expression of phospho-JNK,Bcl-2 and Bax were detected by Western blot (n =6).One way ANOVA were used for data analysis among groups.Results The number of TUNEL positive cells in the hippocampal CA1 regions in group Iso +D (135.72 ±21.26 per mm2) increased by 5 folds compared with group D (24.07 ± 1.35 per mm2) (P＜0.01) ;while the number of apoptotic cells in group Iso + SP30 (42.49 ± 5.56 per mm2) decreased by 84％ (P ＜ 0.05)compared with group Iso + D.The expression of phospho-JNK p46 kd in group Iso + D increased by 44.1％ (P ＜0.01),while both phospho-JNK at p46kd and at p54kd in group Iso + SP30 decreased significantly (P＜0.05,P ＜0.01) compared with group Iso + D.The protein expression of Bax increased 1.5 folds (P＜0.05) and Bcl-2 decreased by 42.2％ (P＜0.05) in group Iso + D compared to group D;while SP600125 significantly decreased expression of Bax (P ＜0.05) and increased expression of Bcl-2 (P＜0.01).Conclusion JNK activation contributes to isoflurane-induced neuroapoptosis in the developing brain.Maintaining Bcl-2 expression and inhibiting Bax expression may be involved in the neuroprotective effects of SP600125.