N-甲基-D-天冬氨酸受体介导的脊髓缺血-再灌注保护作用的研究  

Protection of spinal cord ischemia-reperfusion injury mediated by N-methyl-Daspartate receptors

作　　者：陈宏[1] 陈苏伟 王盛宇[1] 李岩[1] 孟旭[1] CHEN Hong;CHEN Suwei;WANG Shengyu;LI Yan;MENG Xu(Department of Cardiac Surgery,Beijing Anzhen Hospital,Capital Medical University,Beijing,100029,P.R.China)

机构地区：[1]首都医科大学附属北京安贞医院心外科,北京100029

出　　处：《中国胸心血管外科临床杂志》2020年第12期1460-1465,共6页Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

摘　　要：目的探讨N-甲基-D-天冬氨酸(NMDA)受体介导的脊髓缺血-再灌注的保护机制。方法将42只SD大鼠随机分为4组:非阻断组(n=6)、生理盐水组(n=12)、NMDA受体阻断剂K-1024(25 mg/kg)组(n=12)和电压门控Ca2+通道阻断剂尼莫地平(0.5 mg/kg)组(n=12),各组药物缺血前30 min腹腔注射。评价神经功能,观察并比较腰段脊髓组织学变化、神经递质氨基酸的释放、脊髓神经元型一氧化氮合成酶(nNOS)蛋白表达情况。结果再灌注8 h时,K-1024组大鼠行为学评分为(2.00±0.00)分,与生理盐水组[(5.83±0.41)分]和尼莫地平组[(5.00±1.00)分]相比差异有统计学意义(P<0.05)。K-1024组与生理盐水组和尼莫地平组相比运动神经元损伤更小。在缺血10 min后,各组谷氨酸浓度差异无统计学意义(P=0.731);K-1024组与生理盐水组比较nNOS蛋白表达明显下调(P<0.01)。再灌注8 h后,K-1024组与生理盐水组比较nNOS蛋白表达明显上调(P<0.05)。结论脊髓缺血期,K-1024是通过抑制NMDA受体,下调nNOS蛋白表达发挥脊髓保护作用;再灌注期,K-1024对脊髓的功能、结构和神经细胞生物活性有较好的保护作用。Objective To analyze the protective mechanism of spinal cord ischemia-reperfusion injury mediated by N-methyl-D-aspartate(NMDA)receptor.Methods A total of 42 SD rats were randomly assigned to 4 groups:a nonblocking group(n=6),a saline group(n=12),a NMDA receptor blocker K-1024(25 mg/kg)group(n=12)and a voltagegated Ca2+channel blocker nimodipine(0.5 mg/kg)group(n=12).The medications were injected intraperitoneally 30 min before ischemia.The neural function was evaluated.The neuronal histologic change of spinal cord lumbar region,the release of neurotransmitter amino acids and expression of spinal cord neuronal nitric oxide synthase(nNOS)were compared.Results At 8 h after reperfusion,the behavioral score of the K-1024 group was 2.00±0.00 points,which was statistically different from those of the saline group(5.83±0.41 points)and the nimodipine group(5.00±1.00 points,P<0.05).Compared with the saline group and nimodipine group,K-1024 group had more normal motor neurons(P<0.05).There was no significant difference in glutamic acid concentration in each group at 10 min after ischemia(P=0.731).The nNOS protein expression in the K-1024 group was significantly down-regulated compared with the saline group(P<0.01).After 8 h of reperfusion,the expression of nNOS protein in the K-1024 group was significantly upregulated compared with the saline group(P<0.05).Conclusion K-1024 plays a protective role in spinal cord ischemia by inhibiting NMDA receptor and down-regulating nNOS protein expression;during the reperfusion,K-1024 has a satisfactory protective effect on spinal cord function,structure and biological activity of nerve cells.

关 键 词：脊髓缺血-再灌注 K-1024 谷氨酸 神经元型一氧化氮合成酶(nNOS) N-甲基-D-天冬氨酸(NMDA)受体 

分 类 号：R654.3[医药卫生—外科学]