胍基丁胺通过调节Nrf2/HO-1信号通路减轻丙泊酚诱导的新生大鼠的神经毒性  

Agmatine attenuates propofol-induced neurotoxicity in newborn rats by regulating the Nrf2/HO-1 signaling pathway

作　　者：张少华[1] 张彦芳 曹萌[2] 李燕[2] 廖立夏 王贝贝[1] ZHANG Shaohua;ZHANG Yanfang;CAO meng;LI Yan;LIAO Lixia;WANG Beibei(Department of Pediatrics,Nanyang First People’s Hospital,Nanyang 473000,China;the Second Department of Endocrinology,First Affiliated Hospital of Xinxiang Medical University,Xinxiang 453100)

机构地区：[1]南阳市第一人民医院儿一科,河南南阳473000 [2]新乡医学院第一附属医院内分泌二病区,河南新乡453100

出　　处：《中国比较医学杂志》2020年第12期17-22,119,共7页Chinese Journal of Comparative Medicine

基　　金：河南省医学科技攻关项目(20150311)。

摘　　要：目的本文旨在探讨胍基丁胺对丙泊酚诱导的新生大鼠的神经毒性的影响。方法通过腹腔注射丙泊酚诱导神经损伤模型将大鼠分为5组:Control组、Propofol组、Propofol+Agmatine 1.25 mg/kg组、Propofol+Agmatine 2.5 mg/kg组和Propofol+Agmatine 5 mg/kg组。跳台实验检测犯错次数,2,3,5-三苯基氯化四氮唑法检测脑含水率、脑指数,Longa法评价神经功能缺陷评分、姿势反射评分HE染色检测海马区病理损伤程度,Nissl染色检测海马区组织凋亡,蛋白免疫印迹检测各组大鼠脑组织BDNF、NGF、Bax、Bcl-2、Nrf2、p-Nrf2、HO-1蛋白表达水平。结果结果表明,与Control组相比较,Propofol组犯错次数显著升高(P<0.05),脑含水率、脑指数显著升高(P<0.05),神经功能缺陷评分、姿势反射评分显著升高(P<0.05),呈现明显病理损伤,BDNF、NGF蛋白水平显著降低(P<0.05),Nissl小体数目明显减少,Bax/Bcl-2比值显著升高(P<0.05),p-Nrf2/Nrf2比值和HO-1蛋白水平显著降低(P<0.05)。与Propofol组相比较,Propofol+Agmatine 2.5、5 mg/kg组犯错次数显著降低(P<0.05),脑含水率、脑指数显著降低(P<0.05),神经功能缺陷评分、姿势反射评分显著降低(P<0.05),病理损伤程度明显改善,BDNF、NGF蛋白水平显著升高(P<0.05),Nissl小体数目明显增多,Bax/Bcl-2比值显著降低(P<0.05),p-Nrf2/Nrf2比值和HO-1蛋白水平显著升高(P<0.05)。结论胍基丁胺通过调节Nrf2/HO-1信号通路减轻丙泊酚诱导的新生大鼠的神经毒性。Objective To investigate the effects of agmatine on Propofol-induced neurotoxicity in newborn rats.Methods Rats were divided into five groups for follow-up experiments:Control,Propofol,Propofol+1 mg/kg Agmatine,Propofol+2.5 mg/kg Agmatine,and Propofol+5 mg/kg Agmatine.The number of errors was detected in a platform experiment,while brain moisture content and brain index were determined by a 2,3,5-triphenyl tetrazolium chloride method.The Longa method was used to evaluate neural functional defect and postural reflex scores.HE staining was used to detect the degree of pathological damage in the hippocampus.Apoptosis of hippocampal tissue was detected by Nissl staining.Western blot was used to detect protein expression levels of brain-derived neurotrophic factor(BDNF),nerve growth factor(NGF),Bax,Bcl-2,Nrf2,p-Nrf2,and heme oxygenase 1(HO-1).Results Compared with the Control group,the Propofol group exhibited significant increases in the number of platform errors(P<0.05),brain water content and cerebral index(P<0.05),neural function defect scores,and posture reflex scores(P<0.05),as well as obvious pathological damage.Moreover,the Propofol group exhibited significantly reduced expression of BDNF,NGF,and HO-1 proteins(P<0.05),p-Nrf2/Nrf2 ratio(P<0.05),and numbers of Nissl bodies(P<0.05),but a significantly higher Bax/Bcl-2 ratio(P<0.05).Compared with the Propofol group,Propofol+Agmatine groups(2.5 and 5 mg/kg)exhibited significantly decreased numbers of platform errors(P<0.05),brain water content and cerebral index(P<0.05),neurologic deficit scores(P<0.05),and posture reflex scores(P<0.05).Moreover,the degree of pathological damage was significantly improved in Propofol+Agmatine groups,which exhibited significantly increased BDNF and NGF protein expression(P<0.05),and numbers of Nissl bodies(P<0.05),and a significantly decreased Bax/Bcl-2 ratio(P<0.05).p-Nrf2/Nrf2 ratio and HO-1 protein expression were also significantly increased(P<0.05).Conclusions Agmatine attenuates Propofol-induced neurotoxicity in newborn rats b

关 键 词：胍基丁胺 丙泊酚 凋亡 Nrf2/HO-1信号通路 

分 类 号：R-33[医药卫生]