摘要
目的 观察鞘内注射右美托咪啶在兔脊髓缺血再灌注损伤后对脊髓前角神经元功能和p-ERK mRNA表达的影响.方法 成年雄性日本白兔24只,建立兔脊髓缺血再灌注（ischemiareperfusion injury,I/R）模型（缺血30 min,再灌注24 h）.按随机数字表法分为假手术组（sham）、缺血再灌注损伤组（I/R组）、右美托咪啶（dexmedetomidine,DEX）鞘内注射组（DEX组,缺血前鞘内注射右美托咪啶1 μg/kg）和右美托咪啶抑制剂鞘内注射组（DEX＋ ATIP组,缺血前鞘内注射右美托咪啶＋阿替美唑）.各组分别于缺血后24 h处死动物进行组织学检查,采用干湿法测定脊髓含水量,测定脊髓组织超氧化物歧化酶（superoxide dismutase,SOD）、丙二醛（malondialdehyde,MDA）含量,并采用免疫蛋白印迹杂交测定总细胞外信号调节蛋白激酶（t-ERK）、磷酸化细胞外信号调节蛋白激酶（pERK）和Caspase3表达水平.结果 缺血再灌注损伤24h后,与I/R组相比,DEX组脊髓灰质前角内健存运动神经元数量明显增多（F =14.32,P＜0.05）,脊髓含水量降低（F=13.6,P＜0.05）,免疫蛋白印迹杂交测定p-ERK表达增加（F=22.37,P＜0.05）和Caspase3表达降低（F=15.45,P ＜0.05）.而鞘内注射DEX抑制剂ATIP后保护作用消失.结论 鞘内注射右美托咪啶可以减轻脊髓缺血再灌注损伤,可能与其增加脊髓前角p-ERK的蛋白表达有关.
Objective To investigate the beneficial effects and possible mechanisms of intrathecal injection of dexmedetomidine （DEX） in protection of spinal cord ischemia-reperfusion injury.Methods Spinal cord ischemia-reperfusion injury was induced in rabbits by infrarenal aortic occlusion for 30 minutes.Twenty-four rabbits were randomly divided into four groups：sham group,I/R group,DEX group （1 μg/kg dexmedetomidine by intrathecal injection）,DEX ＋ ATIP group （1 μg/kg dexmedetomidine and 0.5 μg/kg atipamezole （ATIP） by intrathecal injection）.Physiological indices were assessed and motor neurons in the ventral gray matter were counted by histological examination.The expression of total extracellular signal-related kinase （t-ERK）,phospho-extracellular signal-related kinase （p-ERK）,and caspase 3 were assessed by Western blotting and real-time polymerase chain reaction （RT-PCR）.The water content in spines was also measured.Results Intrathecal injection of dexmedetomidine minimized the neuromotor dysfunction and histopathological deficits（F =14.32,P 〈 0.05） and attenuated the influences of peroxidation at 24 hours after spinal cord ischemia-reperfusion injury.The physical indices during experiment were comparable among all groups.In addition,intrathecal injection of dexmedetomidine reduced the excessive expression of caspase 3 mediated by ERK signal pathway（F =15.45,P 〈 0.05）.Conclusions Pre-emptive intrathecal injection of dexmedetomidine produced beneficial effects on spinal cord after spinal cord ischemia-reperfusion injury in a rabbit model of transient aortic occlusion.This beneficial effect was partly attributed to the inhibition of caspase 3 mediated by ERK signal pathway,which represents a potential therapeutic approach to mitigate spinal cord injury after aortic occlusion.
出处
《中国医师杂志》
CAS
2013年第8期1032-1036,共5页
Journal of Chinese Physician
基金
基金资助：2009年度博士点基金项目（20092104110009）
关键词
右美托咪啶
投药和剂量
注射
脊髓
再灌注损伤
脊髓
兔
Dexmedetomidine/administration ＆ dosage
Injections, spinal
Reperfusion injury
Spinal cord
Rabbits
