Role of ornithine decarboxylase/polyamine pathway in focal cerebral ischemia-reperfusion injury and its mechanism in rats.

Objective: To observe the role of ornithine decarboxylase (ODC)/polyamine pathway in focal cerebral ischemia-reperfusion injury and to explore its mechanism in rats.

Methods: This study was randomly divided into 3 groups including sham-operation (sham) group, ischemia-reperfusion (I/R) group and α-difluoromethylornithine (DFMO) group (each group with 80 rats). In DFMO group, 300 mg/kg of DFMO was injected by tail vein 24 h before reperfusion. According to different time points (3 h, 12 h, 24 h, 48 h and 72 h) after reperfusion, each group was divided into 5 subgroups (each subgroup with 16 rats).

Results: In I/R group, apoptosis began increasing 3 h after reperfusion, reached a peak 24 h after perfusion and began decreasing 48 h after perfusion. Compared with sham group, apoptosis significantly increased in I/R and DFMO groups (P<0.05). However, apoptosis was significantly lower in DFMO group than in I/R group at each time point (P<0.05). In I/R group, CHOP expression began increasing 3 h after reperfusion, reached a peak 24 h after perfusion and began decreasing 48 h after perfusion. CHOP expression was significantly lower in DFMO group than in I/R group at each time point (P<0.05). The level of polyamines was significantly higher in I/R and DFMO groups than in sham group, and in I/R group than in DFMO group 12 h, 24 h and 48 h, respectively (P<0.05).

Conclusions: Down-regulation of ODC/polyamine pathway may inhibit CHOP-mediated apoptosis caused by endoplasmic reticulum stress and plays a protective role in cerebral I/R injury.