胞磷胆碱对新生大鼠缺氧缺血脑损伤的保护作用机制研究  

Protective effects and mechanism of citicoline on hypoxic-ischemic brain damage in neonatal rats

作　　者：李柳依 甘容 刘俊丹 LI Liu-yi;GAN Rong;LIU Jun-dan(Department of Neonatal,Yongzhou Maternal and Child Health Hospital,Yongzhou 425000,Hunan Province,China;Department of Neonatal,Hunan Children’s Hospital,Changsha 410007,Hunan Province,China)

机构地区：[1]永州市妇幼保健院新生儿科,湖南永州425000 [2]湖南省儿童医院新生儿科,湖南长沙410007

出　　处：《中国临床药理学杂志》2021年第14期1828-1831,共4页The Chinese Journal of Clinical Pharmacology

基　　金：湖南省医学科学重点基金资助项目(2017115)。

摘　　要：目的研究胞磷胆碱对在低氧应激中的未成熟动物的保护作用机制。方法按照体重将新生大鼠幼鼠分为3组:正常组、模型组和实验组,每组8只。大鼠右颈动脉静置2 h后在33℃的8%O2低氧环境中休息2 h来复制缺氧缺血脑损伤模型。造模3 d后,模型组腹膜内注射磷酸盐缓冲液0.2 mL,实验组大鼠腹膜内注射50 mg·kg^(-1)胞磷胆碱0.2 mL。评估幼鼠损伤后剩余脑体积百分率和大脑皮质中小胶质细胞的相对密度值,以蛋白质印迹法检测Caspase-1蛋白和3个核苷酸结合低聚结构域样受体(NLRP3)炎性小体的表达水平。结果正常组、模型组和实验组的剩余脑体积分别为(100.00±12.00)%,(42.27±4.18)%和(60.97±6.23)%;这3组的大脑皮质中小胶质细胞的相对密度值分别为(100.00±9.27)%,(426.08±40.91)%和(202.11±23.27)%;这3组的Caspase-1的表达分别为(100.20±10.09)%,(403.50±40.21)%和(121.46±10.13)%;这3组的NLRP3的炎症小体活化水平分别为(100.30±11.02)%,(310.46±32.14)%和(163.70±13.63)%。模型组与正常组相比或者实验组与模型组相比,差异均有统计学意义(均P<0.05)。结论胞磷胆碱可通过抑制NLRP3减轻新生鼠的缺氧缺血性脑损伤炎性体激活。Objective To investigate protective role and its mechanism of citicoline on the hypoxic-ischemic brain damage in neonatal rats.Methods The neonatal rats were divided into 3 groups according to weight:Normal group,model group and experimental group,8 rats in each group.The right carotid artery of rats was allowed to stand for 2 h,and then rested in an 8%O2 hypoxic environment at 33℃for 2 h to replicate the hypoxic-ischemic brain injury model.Three days later,the model group was injected intraperitoneally with PBS(0.2 mL),and the experimental group was injected intraperitoneally with citicoline(50 mg·kg^(-1),0.2 mL).Afterwards,percentage of residual brain volume after injury was evaluated,and relative density of microglia in cerebral cortex were detected.And the Caspase-1 expression and the activation signal and inactivation signal of three nucleotide binding oligomerization domain-like receptors(NLRP3)inflammasome activation were detected by Western blot.Results The remaining brain volume of the normal group,model group and experimental group were(100.00±12.00)%,(42.27±4.18)%and(60.97±6.23)%,respectively;the relative density values of microglia in the 3 groups were(100.00±9.27)%,(426.08±40.91)%and(202.11±23.27)%,respectively;the expression of Caspase-1 in the 3 groups were(100.20±10.09)%,(403.50±40.21)%and(121.46±10.13)%,respectively;the inflammasome activation levels of NLRP3 in the 3 groups were(100.30±11.02)%,(310.46±32.14)%and(163.70±13.63)%,respectively.Comparison between model group and normal group,the difference of the factors were significant(all P<0.05);comparison between experimental group and model group,the difference was significant(all P<0.05).Conclusion Citicoline can alleviate inflammatory body activation of hypoxic-ischemic brain damage in neonatal rats by inhibiting NLRP3.

关 键 词：胞磷胆碱 新生儿 缺氧缺血 脑损伤 3个核苷酸结合低聚结构域样受体 

分 类 号：R97[医药卫生—药品]