Protective role of mitochondrial division inhibitor and its mechanism in rats with cerebral ischemia/reperfusion injury / 中华神经医学杂志

ABSTRACT

Objective To observe the effect ofmitochondrial division inhibitor (Mdivi-1) on the neuronal apoptosis via mitochondria signaling pathways in rats after cerebral ischemia/reperfusion (I/R) and its possible mechanism.Methods Sixty male adult healthy Wistar rats were chosen and randomly divided into sham-operated group,vehicle group and Mdivi-1 pre-conditioning group (n=20); animal models of middle cerebral artery occlusion/reperfusion in the later 2 groups were established by a filament method in the left extemal-internal carotid artery.Rats were injected with 1.2 mg/kg Mdivi-1 in the Mdivi-1 pre-conditioning group and dimethyl sulfoxide in the vehicle group 15 minutes before the cerebral ischemia.After 24 h of reperfusion,apoptotic cell death was assessed by TUNEL staining,the cytochrome C expression (Cyt C) was detected by SABC immunohistochemical staining,the protein level of Cyt C in the cerebral issues was detected by Western blotting and the mRNA expression was measured by semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR).Results The apoptosis rate (45.49％±0.77％),Cyt C positive cell rate (55.12％±1.47％) and protein and mRNA expressions of Cyt C (0.932 ±0.001,0.789±0.009) in the vehicle group were significantly higher that in the sham-operated group (4.16％±0.25％,4.22％±0.20％,0.395±0.002,0.467±0.003,P＜0.05).The apoptosis rate (45.49％±0.77％),Cyt C positive cell rate (55.12％±1.47％) and protein and mRNA expressions of Cyt C (0.594±0.002,0.523±0.004) in the Mdivi-1 pre-conditioning group were significantly decreased as compared with those in the vehicle group (P＜0.05).Conclusion Mitochondrial division inhibitor Mdivi-1 might reduce neuronal apoptosis by inhibiting mitochondria cytochrome C apoptotic pathway to protect cerebral against ischemia/ reperfusion injury.