[Effect of recombinant human erythropoietin on hippocampal p-Akt and caspase-9 expressions in rats with status epilepticus and the mechanism].
OBJECTIVE
To observe the effect of recombinant human erythropoietin (rhuEPO) on p-Akt and caspase-9 expressions in the hippocampus of rats with status epilepticus (SE) and explore the neuroprotective mechanism of rhuEPO.


METHODS
Adult male SD rats were randomized into control, PTZ, rHuEPO, LY294002 group, and DMSO groups and treated with normal saline (NS), PTZ, PTZ+rHuEPO, PTZ+LY294002+rHuEPO, and PTZ+DMSO+rHuEPO, respectively. The behavioral and electroencephalogram (EEG) changes of the rats were recorded, and the expressions of p-Akt and caspase-9 were detected using immunohistochemistry. The hippocampal expression of caspase-9 mRNA was detected using RT-PCR, and the expressions of Akt and p-Akt proteins were determined with Western blotting.


RESULTS
The p-Akt-positive cell and p-Akt protein expression increased significantly while the caspase-9-positive cell and caspase-9 mRNA expression decreased in rHuEPO group as compared with those in PTZ group (P<0.05). LY294002 treatment prior to rHuEPO injection significantly abolished the effects of rHuEPO on caspase-9 and p-Akt immunohistochemical positivity and caspase-9 mRNA and p-Akt protein expressions (P<0.05).


CONCLUSIONS
Administration of rHuEPO activates the PI3K/Akt signaling pathway in SE rats and increases the expression of p-Akt protein to regulate the expression of caspase-9, a regulatory factor of the mitochondrial-dependent apoptotic pathway, and therefore provides anti-apoptotic and neuroprotective effects.
Wang
Wei-ping
WP
Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang 050000, China. LDH_WWP_LCY @163.com
Shi
Zhi-qin
ZQ
Yu
Jiang-hua
JH
Guo
Li
L
Wang
Le
L
Han
Dong-liang
DL
Yuan
Dong-cai
DC
Zang
Ying-zhuo
YZ
D000818:Animals; D053453:Caspase 9 / Q000235:genetics / Q000378:metabolism*; D004921:Erythropoietin / Q000627:therapeutic use*; D006624:Hippocampus / Q000378:metabolism*; D008297:Male; D018696:Neuroprotective Agents / Q000627:therapeutic use; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins; D013226:Status Epilepticus / Q000188:drug therapy* / Q000378:metabolism
D018696:Neuroprotective Agents; D012333:RNA, Messenger; D011994:Recombinant Proteins; D004921:Erythropoietin; C494920:Akt1 protein, rat; D051057:Proto-Oncogene Proteins c-akt; C506435:Casp9 protein, rat; D053453:Caspase 9