美金刚对永久性大脑中动脉栓塞大鼠早期神经保护作用  

Neuroprotective effect of memantine on early permanent middle cerebral artery occlusion rats

作　　者：王一 孙中武[2] 杨玉红 WANG Yi;SUN Zhong-wu;YANG Yu-hong(Department of Neurology,Chuzhou Hospital Affiliated to Anhui Medical University,Chuzhou 239001,Anhui Province,China;Department of Neurology,The First Affiliated Hospital of Anhui Medical University,Hefei 230022,Anhui Province,China)

机构地区：[1]安徽医科大学附属滁州医院神经内科,安徽滁州239001 [2]安徽医科大学第一附属医院神经内科,安徽合肥230022

出　　处：《中国临床药理学杂志》2023年第13期1904-1907,共4页The Chinese Journal of Clinical Pharmacology

基　　金：安徽省重点研究与开发计划基金资助项目(202104j07020031)。

摘　　要：目的 研究美金刚(MEM)对永久性大脑中动脉栓塞(pMCAO)大鼠早期神经保护作用,并探讨相关机制。方法 将36只大鼠随机分为假手术组、模型组与实验组,每组12只。用线栓法构建大鼠pMCAO模型,假手术组仅分离颈动脉但不进行结扎与栓塞。实验组于建模成功后5 min与12 h腹腔注射20 mg·kg^(-1)和1 mg·kg^(-1)美金刚;假手术组与模型组注射等量磷酸盐缓冲液。末次给药12 h后,用Longa法对各组大鼠进行神经功能评分;用2,3,5-氯化三苯基四氮唑(TTC)染色检测大脑梗死体积并计算梗死率;用原位末端标记(TUNEL)法检测细胞凋亡情况;用蛋白质印迹法检测脑组织中c-Jun氨基末端激酶(JNK)、p38丝裂原激活蛋白激酶(p38MAPK)蛋白表达水平。结果 假手术组、模型组与实验组的神经功能评分分别为0、(3.26±0.51)和(2.09±0.33)分;脑梗死率分别为0、(44.71±6.50)%和(19.83±2.57)%;每个视野细胞凋亡数分别为(4.17±1.01)、(67.18±9.67)和(18.31±3.11)个;JNK蛋白表达水平分别为0.08±0.01、1.35±0.28和0.61±0.12;p38MAPK蛋白表达水平分别为0.27±0.06、1.33±0.31和0.58±0.15,模型组与假手术和实验组比较,差异均有统计学意义(均P<0.05)。结论 美金刚可保护pMCAO大鼠模型的神经元,可能通过抑制JNK/p38MAPK信号通路实现。Objective To explore the neuroprotective effect of memantine(MEM)on early permanent middle cerebral artery occlusion(pMCAO)rats and to investigate the possible mechanism.Methods Thirty-six rats were randomly divided into sham group,model group and experimental group,with 12 rats in each group.The pMCAO rat model was established by thread occlusion method.The sham group only separated the carotid artery but did not ligate and occlude it.The experimental group was intraperitoneally injected with 20 mg·kg^(-1)and 1 mg·kg^(-1)MEM at 5 min and 12 h after successful modeling.The sham group and the model group were injected with equal amount of phosphate buffer solution.Twelve hours after the last administration,the neurological function score of each group was evaluated according to Longa's method.The brain infarct volume was detected by 2,3,5-triphenyltetrazolium chloride(TTC)staining and the infarct rate was calculated.Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling(TUNEL)method was used to detect cell apoptosis.Western blotting was used to detect the protein expression levels of c-Jun N-terminal kinase(JNK)and p38 mitogen-activated protein kinase(p38MAPK)in brain tissue.Results The neurological function scores of the sham group,model group and experimental group were 0,(3.26±0.51)and(2.09±0.33)points;the brain infarct rates were 0,(44.71±6.50)%and(19.83±2.57)%;the number of apoptotic cells per field of view were 4.17±1.01,67.18±9.67 and 18.31±3.11;the protein expression levels of JNK were 0.08±0.01,1.35±0.28 and 0.61±0.12;the protein expression levels of p38MAPK were 0.27±0.06,1.33±0.31 and0.58±0.15;compared sham group and experimental group with model group,the difference were all statistically significant(all P<0.05).Conclusion MEM can protect neurons in pMCAO rat model,which may be achieved by inhibiting JNK/p38MAPK signaling pathway.

关 键 词：美金刚 脑缺血 C-JUN氨基末端激酶 P38丝裂原激活蛋白激酶 神经保护 

分 类 号：R971[医药卫生—药品]