茴拉西坦对局灶性脑缺血再灌注损伤模型大鼠的神经保护作用  

Neuroprotective Effect of Aniracetam on Focal Cerebral Ischemia-Reperfusion Injury in Rats

作　　者：柴娟 张潇潇 李丹[1] 徐沙丽 CHAI Juan;ZHANG Xiaoxiao;LI Dan;XU Shali(Department of Neurology,Liyuan Hospital of Tongji Medical College of Huazhong University of Science and Technology,Wuhan,Hubei,China 430077)

机构地区：[1]华中科技大学同济医学院附属梨园医院神经内科,湖北武汉430077

出　　处：《中国药业》2022年第2期28-31,共4页China Pharmaceuticals

基　　金：华中科技大学自主创新研究基金[2017KFYXJJ088]。

摘　　要：目的探讨茴拉西坦对局灶性脑缺血再灌注损伤(I/R)模型大鼠的神经保护作用。方法将100只SD大鼠分为对照组(等体积0.9%氯化钠溶液)、模型组(等体积0.9%氯化钠溶液)、尼莫地平组(50 mg/kg)和茴拉西坦低、高剂量组(50,100 mg/kg),各20只。复制局灶性脑I/R大鼠模型,建模成功后灌胃相应药物或等体积0.9%氯化钠溶液(每100 g体质量1 mL),每日1次,连续4周。进行贴纸去除及平衡木行走实验,以Longa评分标准评估大鼠的脑神经功能,测定大鼠脑梗死体积;采用逆转录聚合酶链式反应(RT-PCR)法及Western blot法分别测定大鼠脑组织的转录激活子4(ATF4)及NLRP3 mRNA和蛋白的表达水平。结果与模型组比较,尼莫地平组和茴拉西坦低、高剂量组大鼠双侧贴纸去除时间、平衡木过杆时间均显著缩短,脑梗死体积显著缩小,NLRP3mRNA和蛋白的表达水平和Longa评分均显著降低,ATF4 mRNA和蛋白的表达水平均显著升高(P<0.05)。结论茴拉西坦对局灶性脑I/R模型大鼠具有一定神经保护作用,其机制与促进大鼠脑组织ATF4表达、抑制NLRP3表达有关。Objective To investigate the neuroprotective effect of aniracetam on focal cerebral ischemia-reperfusion injury(I/R)in rats.Methods A total of 100 SD rats were divided into the control group(equal volume of 0.9%Sodium Chloride Solution),model group(equal volume of 0.9%Sodium Chloride Solution),nimodipine group(50 mg/kg),and aniracetam low-and highdose groups(50,100 mg/kg),with 20 rats in each group.The focal cerebral I/R rat models were established.After successful modeling,the rats were given the corresponding drugs or the equal volume of 0.9%Sodium Chloride Solution(1 mL per 100 g of body weight),once a day for four weeks.The sticker removal test and balance beam walking test were carried out.The cerebral nerve function of rats was evaluated by the Longa score standard,and the cerebral infarction volume was measured.The expression levels of transcription activator 4(ATF4)mRNA and protein and NLRP3 mRNA and protein in brain tissue of rats were measured by reverse transcription-polymerase chain reaction(RT-PCR)and Western blot respectively.Results Compared with those in the model group,the bilateral stickers removal time and the balance beam passing time were significantly shortened,the cerebral infarction volume was significantly reduced,the expression levels of NLRP3 mRNA and protein and Longa score were significantly reduced,while the expression levels of ATF4 mRNA and protein were significantly increased in the nimodipine group and aniracetam low-and high-dose groups(P<0.05).Conclusion Aniracetam has a neuroprotective effect on focal cerebral I/R model rats,and its mechanism is related to promoting the expression of ATF4 and inhibiting the expression of NLRP3.

关 键 词：茴拉西坦 脑缺血再灌注损伤 ATF4/NLRP3通路 神经保护 大鼠 

分 类 号：R965[医药卫生—药理学] R971[医药卫生—药学]