5-(4-羟基-3-甲氧基苯亚甲基)罗丹宁对大鼠脑缺血再灌注损伤的保护作用及机制研究  

Protective effect and its mechanism of 5-(4-hydroxy-3-methoxybenzylidene)rhodanine on cerebral ischemia-reperfusion injury

作　　者：刘自然 霍东升[1] 贾建新[1] 杨占君[1] LIU Ziran;HUO Dongsheng;JIA Jianxin;YANG Zhanjun(Department of Anatomy,Baotou Medical College,Baotou,014000,China)

机构地区：[1]包头医学院解剖教研室,内蒙古包头014000

出　　处：《中国比较医学杂志》2019年第2期37-42,共6页Chinese Journal of Comparative Medicine

基　　金：内蒙古自治区高等学校科学技术研究项目(NJZZ16197)

摘　　要：目的探讨罗丹宁衍生物(rhodanine-1,RD-1)对脑缺血再灌注损伤的保护作用及机制。方法制作大鼠MCAO模型后缺血2 h,再灌注24 h,以神经行为评分和脑梗死体积数值评价RD-1对脑缺血再灌注损伤的保护作用;检测超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-Px)的活性,丙二醛(MDA)的含量,以及Bax,Bcl-2,caspase-3蛋白的表达,探讨其脑保护作用的机制。结果与模型组比较,RD-1低、中、高剂量组神经行为学评分及脑梗死体积比均显著降低(P<0. 05);与模型组比较,RD-1低、中、高剂量脑组织超氧化物歧化酶(SOD),谷胱甘肽过氧化物酶(GSH-Px)活性明显升高,而丙二醛(MDA)含量则显著降低(P<0. 05);与模型组比较,RD-1低、中、高剂量组Bax和caspase-3蛋白表达水平降低,Bcl-2蛋白表达水平升高。结论 RD-1对大鼠脑缺血再灌注损伤有保护作用,其机制可能与提高SOD和GSH-Px活性,降低MDA含量,进而具有的抗氧化作用有关。以及上调Bcl-2蛋白表达,下调Bax、caspase-3蛋白表达,进而对抗神经细胞凋亡有关。Objective To investigate the protective effects and mechanisms of action of rhodanine against cerebral ischemia-reperfusion injury.Methods A rat model of middle cerebral artery occlusion(MCAO)was created by exposure to ischemia for2 h and reperfusion for24 h.Neuroprotective score and cerebral infarction volume were used to evaluate the protective effects of rhodanine against cerebral ischemia-reperfusion injury.The superoxide dismutase(SOD)activity,the activity of glutathione peroxidase(GSH-Px)and the level of malondialdehyde(MDA)were detected.The expression of Bax,Bcl-2,and caspase-3 proteins were explored to reveal the brain-protective mechanism.Results Compared with those in the model group,the neurobehavioral scores and cerebral infarction volume ratios of the groups with low,medium,and high dose rhodanine were significantly lower(P<0.05).Compared with those in the model group,the activity levels of SOD and glutathione peroxidase(GSH-Px)in brain tissue were significantly increased in the groups with low,medium,and high dose rhodanine,while their malondialdehyde(MDA)levels were significantly decreased(P<0.05).The expression levels of Bax and caspase-3 were decreased and the expression of Bcl-2 protein was increased in the low-,medium-,and high-dose groups.Conclusions Rhodanine has protective effects against cerebral ischemia-reperfusion injury,and its mechanism may be related to the improvement of SOD and GSH-Px activity,the decrease of MDA level,and an antioxidative effect.Upregulation of Bcl-2 protein expression and downregulation of Bax and caspase-3 protein expression may also be involved,indicating a relationship with neuronal apoptosis.

关 键 词：5-(4-羟基-3-甲氧基苯亚甲基)罗丹宁 脑缺血再灌注 抗氧化 细胞凋亡 

分 类 号：R-33[医药卫生]