[Effect of adrenomedullin on neuron apoptosis and early growth response gene-1 after focal ischemia/ reperfusion in rats].
OBJECTIVE
To explore the influence of adrenomedullin (ADM) on apoptosis of neuron, volume of infarction and the expression of early growth response gene-1 (Egr-1) mRNA in the rat with focal ischemia/reperfusion (I/R) injury.


METHODS
Fifty-four SD rats were randomly divided into sham operation group, ADM femoral vein group, internal carotid artery group and lateral cerebral ventricle group. The model was reproduced by ligating the middle cerebral artery (MCA) with a ligature for 2 hours followed by injection of ADM through femoral artery, internal carotid artery and lateral cerebral ventricle before reperfusion for 22 hours. The volume of infarction was estimated with tetrazolium chloride (TTC) staining, apoptosis of the neuron was detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) method, the positive expression of Egr-1 mRNA was detected by in-situ hybridization.


RESULTS
The volume of infarction were smaller after the injection of ADM through different ways than that of I/R group. The result was better when the internal carotid artery and the lateral cerebral ventricle were used than that after injection by the way of the femoral vein (both P<0.05). There were few positive cells with TUNEL staining in the cerebral cortex and hippocampus CA1 zone in the sham operation group, and more apoptotic cells were seen in the group with focal brain I/R injury (both P<0.01). After the administration of ADM, especially through the internal carotid artery and the lateral cerebral ventricle, the number of the positive cells with TUNEL staining was decreased obviously compared with I/R group (both P<0.01). There was a little positive expression of Egr-1 mRNA in the cerebral cortex and hippocampus CA1 zone in sham operation group. The expression was enhanced in the group with focal brain I/R injury (both P<0.01). With the injection of ADM, the expression was much more enhanced, especially when internal carotid artery and the lateral cerebral ventricle were used for injection compared with those in I/R group (both P<0.01).


CONCLUSIONS
The injection of ADM through different ways can reduce the neural injury, decrease the apoptosis of the neurons and the volume of the infarction, and increase the expression of Egr-1 mRNA. Therefore, it is efficacious in the treatment of cerebral ischemia.
Bi
Guo-rong
GR
Department of Neurology, Second Affiliated Hospital, China Medical University, Shenyang 110004, Liaoning, China. biguorongcmu@sina.com
Zhang
Hui
H
Zhou
Hui-jie
HJ
Bai
Li-juan
LJ
Zhang
He-min
HM
Hai
Hong
H
Fang
Xiu-bin
XB
D053607:Adrenomedullin / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001921:Brain / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D051766:Early Growth Response Protein 1 / Q000378:metabolism*; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism / Q000473:pathology; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology*
D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D012333:RNA, Messenger; D053607:Adrenomedullin