The protective effect of dexmedetomidine against focal cerebral ischemia/reperfusion injury in rats and its mechanism
10.3760/cma.j.issn.1674-6554.2016.02.005
- VernacularTitle:右美托咪定对大鼠局灶性脑缺血／再灌注损伤的保护作用及机制
- Author:
Cancan WANG
;
Jian YU
- Publication Type:Journal Article
- Keywords:
Dexmedetomidine;
Middle cerebral artery occlusion;
PI3K;
Akt;
Endothelial nitric oxide sythanse
- From:
Chinese Journal of Behavioral Medicine and Brain Science
2016;(2):117-121
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the neuroprotective effect of dexmedetomidine ( Dex) in rats ex-posed to focal cerebral ischemia/reperfusion ( I/R) induced by middle cerebral artery occlusion ( MCAO) and the possible mechansims.Methods Adult male Sprague-Dawley rats were subjected to MCAO for 90 min followed by reperfusion for 24 h and Dex ( 15μg? kg-1 ) was infused through the left femoral vein im-mediately after the onset of MCAO.The PI3K inhibitor LY294002 ( LY,10 mM,10 μl) or eNOS inhibitor L-NIO ( 1 mg? kg-1 ,10μl) was intracerebroventricular administered before ischemia using a microinjecton. The neurological deficit score,brain edema,cerebral infarct volume,and neuron survivals were evaluated after 24 h of reperfusion.The expression of p-Akt ( Ser473) and p-eNOS ( Ser1177) in the ischemic hemicere-brum was detected by Western Blot.Results Compared with I/R group,the neurological deficit score,cere-bral infarct volume,and the degree of brain edema were significantly reduced in the rats treated with Dex ((2.3±0.4) vs (3.9±0.6),(19.3±3.5)%vs (40.5±5.4)%,(61.8±8.1)%vs (76.3±8.5)%,all P<0.05)re-spectively,and the number of survival neuron in the hippocampal CA1 and cortex was significantly increased ((136.5±15.8)/mm vs (53.5±7.9)/mm,(253.8±26.4)/mm3vs (112.5±14.6)/mm3,all P<0.01) respec-tively.The neuroprotection in DEX group was significantly inhibited by LY and L-NIO ( P<0.05) .In addi-tion,the expression of p-Akt and p-eNOS in the ischemic hemicerebrum was markly reduced in LY group compared with that in DEX group ((3.94±0.45) vs (0.85±0.21),(2.14±0.25) vs (0.79±0.29),all P<0.01) ,while there was no significant difference in the expression of p-Akt in the ischemic hemicerebrum be-tween L-NIO group and DEX group ((3.76±0.33) vs (3.94±0.45), P>0.05).Conclusion Dex can reduce cerebral injury in rats exposed to focal I/R,which is mediated by the activation of PI3K/Akt-eNOS pathway.
