基于X连锁凋亡抑制蛋白/第二种线粒体衍生半胱天冬酶激活剂通路探讨尼莫地平对脑梗死大鼠神经功能的影响  

The effect of nimodipine on neurological function in rats with cerebral infarction based on X-linked inhibitor of apoptosis protein/second mitochondrial-derived activator of caspase pathway

作　　者：吴挺国 林慧怡 林文倩 朱福连 龙登毅 Wu Tingguo;Lin Huiyi;Lin Wenqian;Zhu Fulian;Long Dengyi(Department of Neurology,Hainan Senile Hospital,Haikou 571100,China;Department of Internal Medicine,Hainan Senile Hospital,Haikou 571100,China)

机构地区：[1]海南省老年病医院神经内科,海口571100 [2]海南省老年病医院内科,海口571100

出　　处：《心脑血管病防治》2023年第3期12-16,23,共6页CARDIO-CEREBROVASCULAR DISEASE PREVENTION AND TREATMENT

基　　金：海南省自然科学基金(818MS163)。

摘　　要：目的基于X连锁凋亡抑制蛋白(XIAP)/第二种线粒体衍生半胱天冬酶激活剂(Smac)通路探讨尼莫地平对脑梗死大鼠神经功能的影响。方法以线栓法闭塞大鼠大脑中动脉诱导建立大鼠脑梗死模型,随机分为模型组、尼莫地平组(10 mg/kg)、AT-406组(XIAP抑制剂,7 mg/kg)、联合组(尼莫地平联合AT-406),每组12只,另取12只大鼠设定为假手术组,分别给药干预后,以Zea Longa分级法对各组大鼠神经功能缺损进行评分;以Morris水迷宫实验评测各组大鼠学习记忆功能通过比较其跨越原平台次数;以TTC染色检测各组大鼠脑梗死状况;以TUNEL染色评测各组大鼠海马神经元凋亡状况;以试剂盒检测各组大鼠血清促炎因子环氧化酶-2(COX-2)与白细胞介素-18(IL-18)含量;以蛋白免疫印迹法检测各组大鼠脑组织凋亡相关蛋白[B淋巴细胞瘤-2基因(Bcl-2)、Bcl-2相关X蛋白(Bax)]与XIAP/Smac通路相关蛋白(XIAP、Smac)表达状况。结果与假手术组相比,模型组大鼠跨越原平台次数、脑组织Bcl-2与XIAP表达水平显著降低(P<0.05),神经功能缺损评分、脑梗死面积、海马神经元凋亡比率、血清COX-2与IL-18含量、脑组织Bax与Smac表达水平显著升高(P<0.05)。与模型组、联合组分别相比,尼莫地平组大鼠跨越原平台次数、脑组织Bcl-2与XIAP表达水平均升高(P<0.05),神经功能缺损评分、脑梗死面积、海马神经元凋亡比率、血清COX-2与IL-18含量、脑组织Bax与Smac表达水平均降低(P<0.05)。与模型组、联合组分别相比,AT-406组大鼠脑组织跨越原平台次数、脑组织Bcl-2与XIAP表达水平均降低(P<0.05),神经功能缺损评分、脑梗死面积、海马神经元凋亡比率、血清COX-2与IL-18含量、脑组织Bax与Smac表达水平均升高(P<0.05)。结论尼莫地平可通过上调XIAP表达,下调Smac表达,进而抑制炎症,减轻脑梗死大鼠海马神经元凋亡,提升大鼠学习记忆能力,改善其神经功能。Objective To investigate the effect of nimodipine on the neurological function of rats with cerebral infarction based on the X-linked inhibitor of apoptosis protein(XIAP)/second mitochondrial-derived activator of caspase(Smac)pathway.Methods The middle cerebral artery of rats was occluded with suture to induce cerebral infarction model.Then the rats were randomly divided into model group,nimodipine group(10 mg/kg),AT-406 group(XIAP inhibitor,7 mg/kg),union group(nimodipine combined with AT-406),with 12 rats in each group,another 12 rats were set as sham operation group.After grouping and the intervention of the respective drug administration,Zea Longa grading method was used to score the neurological deficit of rats in each group.Morris water maze experiment was used to evaluate the learning and memory function of rats in each group by comparing the number of times of crossing the original platform.TTC staining was used to detect the cerebral infarction status of rats in each group.TUNEL staining was used to evaluate the apoptosis of hippocampal neurons in each group.Kits were used to detect the levels of serum pro-inflammatory factors cyclooxygenase-2(COX-2)and Interleukin-18(IL-18)of rats in each group.Western blotting was used to detect the expression of apoptosis-related proteins[B-cell lymphoma-2(Bcl-2)、Bcl-2-associated X protein(Bax)]and XIAP/Smac pathway-related proteins(XIAP,Smac)in rat brain tissues of each group.Results Compared with the sham operation group,the number of times of crossing the original platform and the expression levels of Bcl-2 and XIAP in the brain tissue of the model group reduced significantly(P<0.05),the neurological deficit score,cerebral infarction area,hippocampal neuron apoptosis ratio,serum COX-2 and IL-18 levels,and Bax and Smac expression levels in brain tissue increased significantly(P<0.05).Compared with the model group and the union group respectively,the number of times of crossing the original platform and the expression levels of Bcl-2 and XIAP in the brain tissue of

关 键 词：X连锁凋亡抑制蛋白/第二种线粒体衍生半胱天冬酶激活剂通路 尼莫地平 脑梗死 神经功能 

分 类 号：R965[医药卫生—药理学]