Neuroprotective effect of pAkt and HIF-1 α on ischemia rats

Abstract

Objective: To explore the neuroprotective effect of pAkt and HIF-1 α on ischemia rats.

Methods: The rat model of cerebral ischemia which induced by permanent middle cerebral artery occlusion was established, Silybin were given respectively. The behavior was measured by modified Longa method, brain water content were measured by the dry-wet method. Infarct volume was measured by image analysis method, Akt, HIF-1 α, Bcl-2, Bax, NF-κ B protein expressions were detected by Western blotting. The Akt, HIF-1 α, Bcl-2, Bax, NF-κ B mRNA expression were detected by RT-PCR.

Results: The control group, low-dose silibinin group and high-dose silibinin group showed paralytic of the left body of rats in various degrees, the brain water content increased and different infarction size. There was no abnormal of the neurobehavioral assessment and no cerebral infarction in the blank group. Compared with the control group, there was no significant improvement of neurological function (t=1.341, P=0.188) or significant changes of the infarct volume (t=1.737, P=0.091) in the low-dose silibinin group, while there was significantly improvement of the neurological function in the high dose silibinin group (t=12.979, P<0.001), and the infarct volume was significantly reduced (t=23.503, P<0.001), the difference had statistically significant. The brain water content of lesion side of the control group increased (t=43.536, P<0.001), while the brain water content of lesion side of the low-dose silibinin group and the high-dose silybin group were significantly reduced (t=25.571, P<0.001; t= 42.426, P<0.001). The differences were statistical significance. The p-Akt 473, p-Akt 308, HIF-1 α, Bax, NF-κ B protein and the Akt, Bax, NF-κ B mRNA expression were increased of the control group, while the Bcl-2 protein and mRNA expression were decreased, the differences were statistically significant (P<0.05), there was no significant change of the Akt protein expression and HIF-1 α mRNA in the control group (P>0.05). In the high dose silybin group, the p-Akt 473, p-Akt 308, HIF-1α, Bcl-2 protein and Akt, Bcl-2 mRNA expression were increased, while the Bax, NF-κ B protein and Bax, NF-κ B mRNA expression were decreased, the differences were statistically significant (P<0.05), there was no significant change of the Akt protein expression and HIF-1 α mRNA in the high dose silybin group (P>0.05).

Conclusions: pAkt, HIF-1 α have neuroprotective effect on ischemia rats.

Keywords: HIF-1 α; Ischemia; Neuroprotection; pAkt.