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作 者:方华[1] 章建平[1] 张竞超[1] 章放香[1] 王泉云[2] 王儒蓉[2] 刘进[2]
机构地区:[1]贵阳医学院附属人民医院麻醉科,贵州贵阳550002 [2]四川大学华西医院麻醉科,四川成都610041
出 处:《中国医院药学杂志》2015年第12期1061-1066,共6页Chinese Journal of Hospital Pharmacy
基 金:贵州省卫生厅基金资助项目(编号:gzwkj2010-1-006;gzwkj2012-1-051);贵州省科技厅基金资助项目[编号:黔科合SY字(2011)008号;黔科SY字(2012)3090号]
摘 要:目的:应用诱发电位监测脊髓电生理的改变,探讨腹主动脉内灌注Mu阿片受体激动剂REM-PCL对Mu阿片受体信号转导介导的神经元保护效果。通过建立兔脊髓缺血再灌注损伤(SCIRI)模型,腹主动脉内灌注Mu阿片受体激动剂REMPCL和选择性Mu阿片受体拮抗剂GSK1521498对Mu阿片受体信号转导介导的神经元保护效果和作用机制进行探讨,并应用诱发电位监测脊髓电生理的改变以及REM-PCL干预后的影响,为临床脊髓保护提供理论和实验依据。方法:30只健康新西兰大白兔随机分为对照组(C组)、REM-PCL组(RP组,0.1 mg·kg-1)和REM-PCL+GSK1521498组(RG组,0.1 mg·kg-1REM-PCL+1 mg·kg-1GSK1521498),每组10只。采用肾下腹主动脉阻断法,建立兔脊髓缺血再灌注损伤(SCIRI)模型。分别于阻断前、再灌注15 min、再灌注30 min、再灌注60 min及再灌注24 h监测血清神经特异性烯醇化酶浓度和MEP变化。再灌注24 h神经行为学评定后取脊髓组织检测Mu阿片受体mRNA表达情况并观察其病理学改变。结果:运动诱发电位可准确反映SCIRI程度。C和RG组血清NSE浓度明显增加而Mu阿片受体mRNA表达明显降低(P<0.01),MEP和脊髓灰质病理损害严重(P<0.01)。RP组血清NSE浓度明显降低而Mu阿片受体mRNA表达明显增加(P<0.01),MEP和脊髓灰质的病理损害程度明显轻于C和RG组(P<0.01),神经行为学评分恢复迅速(P<0.01)。结论:SCIRI能导致脊髓电生理功能损害,应用REM-PCL可以通过激活Mu阿片受体减轻脊髓缺血再灌注损伤。OBJECTIVE To study neuronal protective effects of Mu-opioid receptor( MOR) agonist REM-PCL infused through abdominal aorta by applying evoked potential monitoring electrophysiological changes of spinal cord. METHODS Model of spinal cord ischemia and reperfusion injury( SCIRI) was constructed by clamping the infrarenal aorta in thirty healthy New Zealand white rabbits,which were randomly divided into control group( physiological saline,group C,n = 10),REM-PCL group(0. 1 mg·kg^-1group RP,n = 10) and REM-PCL + GSK1521498 group(0. 1 mg·kg^-1EM-PCL + 1 mg·kg^-1SK1521498,group RG,n = 10). Concentrations of serum NSE and MEP were monitored before ischemia,15 min,30min,60 min and 24 h after reperfusion. Neurologic function was evaluated,spinal cord tissue samples were taken for determining level of MOR mRNA and pathological changes by HE staining 24 h after reperfusion. RESULTS MEP was a sensitive index for spinal cord ischemia and reperfusion injury. Serum level of NSE was significantly higher in group C and RG during reperfusion than in group RP( P〈 0. 01). Level of MOR mRNA was significantly lower in group C and RG during reperfusion than in group RP( P〈 0. 01). Change of MEP and pathological damage to gray matter of spinal cord were more serious in group C and RG during reperfusion than in group RP( P〈 0. 01). Neurologic function score recovered rapidly in group RP during reperfusion( P〈 0. 01). CONCLUSION SCIRI can induce electrophysiologic lesion in spinal cord. However,additional REM-PCL can activate MOR,which can distinctly attenuate SCIRI.
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