摘要
目的:探讨多聚(ADP-核糖)聚合酶1(PARP-1)依赖性细胞死亡(parthanatos)在新生SD大鼠胆红素脑病(BE)中的作用及其潜在机制。方法:选取80只3日龄新生SD大鼠,随机分为对照组和BE组,通过腹腔注射胆红素溶液建立BE模型,采用苏木精-伊红(HE)染色和尼氏染色观察各组大鼠海马病理变化,Western blot检测海马磷酸化组蛋白H2AX(γ-H2AX)、PARP-1和凋亡诱导因子(AIF)蛋白表达,免疫组织荧光染色检测海马AIF的表达情况及分布。结果:与对照组相比,新生SD大鼠注射胆红素12 h后发生黄疸,同时伴随体重增长缓慢。HE染色和尼氏染色结果显示,BE组大鼠海马组织损伤,尼氏体含量减少。Western blot检测结果显示:海马γ-H2AX蛋白表达于造模后72 h开始升高(P<0.05),PARP-1、AIF蛋白水平在72 h后明显升高(P<0.05),免疫组织荧光染色显示:海马AIF的表达升高且出现核易位。结论:经腹腔注射胆红素可诱导新生SD大鼠海马神经元DNA损伤,并激活PARP-1/AIF通路造成大鼠海马神经元PARP-1依赖性细胞死亡。
Objective:To investigate the role and underlying mechanism of parthanatos death in neonatal SD rats with bilirubin encephalopathy(BE).Methods:Eighty 3-day-old neonatal SD rats were selected and randomly divided into control group and BE group.The BE model was established by intraperitoneal injection of bilirubin solution,and the pathological changes in the hippocampus were observed by hematoxylin-eosin(HE)staining and Nissl staining.The protein expressions of the phosphorylation of the core histone protein H2AX(termed gamma H2AX),poly ADP-ribose polymerasw-1(PARP-1)and apoptosis-inducing factor(AIF)in hippocampus were detected by Western blot.Immunofluorescence staining was used to detect the expression and distribution of AIF in hippocampus.Results:Compared with the control group,neonatal SD rats developed jaundice 12 hours after bilirubin injection,accompanied by slow weight gain.HE staining and Nissl staining showed that the hippocampus in BE group were damaged and the content of Nissl bodies was decreased.Western blot results showed that the expression ofγ-H2AX protein in hippocampus began to increase at 72 h after modeling(P<0.05),and the levels of PARP-1 and AIF protein in hippocampus increased significantly at 72 h after modeling(P<0.05).Immunofluorescence staining showed increased AIF expression and nuclear translocation.Conclusion:Intraperitoneal injection of bilirubin can induce DNA damage in hippocampal neurons of neonatal SD rats and activate the PARP-1/AIF pathway to cause parthanatos death of hippocampal neurons.
作者
胡俊楠
李涵
黄麒屹
彭安妮
牛煜媛
谭恒
杜琨
王茜
HU Junnan;LI Han;HUANG Qiyi;PENG Anni;NIU Yuyuan;TAN Heng;DU Kun;WANG Qian(Department of Pathology and Pathophysiology,Faculty of Basic Medical Sciences,Kunming Medical University,Kunming,650000;Department of Neonatology Kunming Children’s Hospital,Kunming 650000,China)
出处
《神经解剖学杂志》
北大核心
2025年第5期606-612,共7页
Chinese Journal of Neuroanatomy
基金
云南省科技厅应用基础研究一般项目(202201AT070197)
昆明医科大学大学生创新创业训练计划项目(J1301307509)
昆明医科大学2022年校级教研教改项目(2022-JY-Y-011)
昆明医科大学2023年院级教研教改项目(J13395001)。
