Influence of ifenprodil pretreatment on focal cerebral ischemia-reperfusion-induced iNOS expression and activity and apoptosis in the ischemic penumbra in rats
10.3760/cma.j.issn.0254-1416.2010.03.032
- VernacularTitle:艾芬地尔预先给药对脑缺血再灌注损伤大鼠缺血半暗带区iNOS和细胞凋亡的影响
- Author:
Yudi ZHOU
;
Kangli HUI
;
Manlin DUAN
;
Jianguo XU
;
Miaomiao XU
- Publication Type:Journal Article
- Keywords:
Piperidines;
Reperfusion injury;
Nitric oxide synthase;
Apoptosis
- From:
Chinese Journal of Anesthesiology
2010;30(3):358-361
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the possible mechanism for the neuroprotective effect of ifenprodil by investigating its effects on inducible nitric oxide synthase (iNOS) expression and activity and apoptosis in the ischemic penumbra following focal cerebral ischemia-reperfusion (I/R) in rats.Methods Fifty-four adult male SD rats weighing 280-320 g were randomly divided into 3 groups ( n = 18 each) : I sham operation group (group S) ; II focal cerebral I/R group (group I/R) and Ⅲ ifenpradil preconditioning group (group IF) received intraperitoneal ifenprodil 10 mg/kg before focal cerebral I/R. Focal cerebral I/R was induced by middle cerebral artery occlusion (MCAO) . A 3-0 nylon thread with rounded tip was inserted into right internal jugular vein and threaded cranially until resistance was met. MCAO was maintained for 2 h. At 48 h after reperfusion, the animals were assessed for neurological function which was scored (0 = no functional deficit, 4 = unable to crawl, unconscious) and then decapitated. The brains were immediately removed for microscopic examination and determination of iNOS protein expression and activity, NO content and apoptosis in the ischemic core (IC) and penumbra (IP). Results Ifenprodil pretreatment significantly decreased the cerebral infarct size and neurological scores in group IF as compared with group I/R. In group I/R the iNOS activity was increased compared with group S.The iNOS activity and NO content were significantly lower in IP than in IC in group IR and IF. The TUNEL-positive cells were also mainly confined to IP. Compared with group I/R, in group IF the iNOS protein expression was significantly down-regulated in IC and IP and the iNOS activity and NO content in IC and IP were suppressed and TUNEL-positive cells were significantly reduced in IP. Conclusion Ifenprodil pretreatment has protective effect against cerebral I/R injury by inhibiting iNOS protein expression in IP, suppressing iNOS activity and NO content and reducing apoptosis.
