[1]刘 伟,吴鸿波,杨红秀,等.β淀粉样蛋白对缺氧缺血性脑损伤新生鼠神经元凋亡影响的实验研究[J].陕西医学杂志,2024,(4):462-467.[doi:DOI:10.3969/j.issn.1000-7377.2024.04.006]
　LIU Wei,WU Hongbo,YANG Hongxiu,et al.Effect of β-amyloid protein on neuronal apoptosis in neonatal rats with hypoxic ischemic brain damage[J].,2024,(4):462-467.[doi:DOI:10.3969/j.issn.1000-7377.2024.04.006]
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β淀粉样蛋白对缺氧缺血性脑损伤新生鼠神经元凋亡影响的实验研究
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《陕西医学杂志》[ISSN:1000-7377/CN:61-1281/TN]

卷:
期数:
2024年4期
页码:
462-467
栏目:
基础研究
出版日期:
2024-04-05

文章信息/Info

Title:
Effect of β-amyloid protein on neuronal apoptosis in neonatal rats with hypoxic ischemic brain damage
作者:
刘 伟; 吴鸿波; 杨红秀; 刘春静; 李丽华
(首都医科大学附属北京潞河医院儿童中心,北京 101100)
Author(s):
LIU Wei; WU Hongbo; YANG Hongxiu; LIU Chunjing; LI Lihua
(Children's Center,Beijing Luhe Hospital Affiliated to Capital Medical University,Beijing 101100,China)
关键词:
β-淀粉样蛋白;  缺氧缺血;  脑损伤;  凋亡;  神经元;  新生鼠
Keywords:
Aβ protein;  Hypoxia-ischemia;  Brain damage;  Apoptosis;  Neuron;  Newbornl rats
分类号:
R -332
DOI:
DOI:10.3969/j.issn.1000-7377.2024.04.006
文献标志码:
A
摘要:
目的:通过建立新生大鼠缺氧缺血性脑损伤(HIBD)模型,以β淀粉样蛋白(Aβ)为切入点,研究其在模型的表达以及与神经元凋亡的关系,探讨Aβ在新生鼠缺氧缺血性脑损伤模型中对神经元的作用及机制。方法:建立10日龄新生大鼠缺血性脑损伤模型,模型后2、4、8、24 h心脏灌注,分别检测脑组织中Aβ、脑内淀粉样前体蛋白(APP)、β-分泌酶(BACE1)、Caspase-3、Cleaved caspase-3、B淋巴细胞瘤-2(Bcl-2)的蛋白表达,BACE1的mRNA表达。使用BACE1抑制剂干预,实验分为三组,缺氧缺血组、抑制剂组和溶剂组,抑制剂组在缺氧缺血后即给予BACE1抑制剂 AZD3293处理24 h后再次检测以上指标。结果:APP、Aβ的蛋白表达、BACE1的蛋白表达和mRNA水平在建模后呈时间依赖的上升,24 h达到高峰。同时,促凋亡蛋白Cleaved caspase-3在建模后也呈时间依赖的上升,24 h达到高峰。而在缺氧缺血2 h后,凋亡抑制蛋白Bcl-2的蛋白水平显著升高(P<0.05)。之后逐渐降低,24 h最低。当使用BACE1抑制剂后,Aβ及BACE1在脑组织中的表达显著下降(均P<0.05),而BACE1mRNA的表达没有变化(P>0.05)。同时促凋亡蛋白Cleaved caspase-3的表达明显下降(P<0.05),同时,Bcl-2蛋白的表达也显著升高(P<0.05)。结论:在新生鼠HIBD时Aβ产生增多,应用BACE1抑制剂可降低Aβ的表达,增加Bcl-2的表达,减轻神经元凋亡。
Abstract:
Objective:To establish a hypoxic ischemic brain damage(HIBD)model in neonatal rats,in order to β amyloid protein(Aβ)as a starting point,study its expression in the model and its relationship with neuronal apoptosis,and explore Aβ The role and mechanism of neurons in a neonatal rat model of hypoxic ischemic brain injury.Methods:A 10 day old neonatal rat model of ischemic brain injury was established.Cardiac perfusion was performed at 2,4,8,and 24 hours after the model was established,and the protein expressions of Aβ,APP,BACE1,Caspase-3,Cleared Caspase-3,and Bcl-2,as well as the mRNA expression of BACE1 in brain tissue were measured separately.Intervention was conducted using BACE1 inhibitors,and the experiment was divided into three groups:hypoxia ischemia group,inhibitor group,and solvent group.The inhibitor group was treated with BACE1 inhibitor AZD3293 for 24 hours after hypoxia ischemia,and the above indicators were detected again.Results:The protein expressions of APP,Aβ,and BACE1 protein and mRNA levels increased in a time-dependent manner after modeling,reaching a peak at 24 hours.At the same time,the pro-apoptotic protein Cleaved caspase-3 also increased in a time-dependent manner after modeling,reaching a peak at 24 hours.After 2 hours of hypoxia and ischemia,the protein level of the apoptosis inhibitory protein Bcl-2 increased significantly(P<0.05).Then it gradually decreases,reaching the lowest level within 24 hours.When BACE1 inhibitor was used,the expressions of Aβ and BACE1 in brain tissue decreased significantly(all P<0.05),while the expression of BACE1 mRNA did not change(P>0.05).At the same time,the expression of pro-apoptotic protein Cleaved caspase-3 decreased significantly,and the expression of Bcl-2 protein increased significantly(all P<0.05).Conclusion:The production of Aβ increases in neonatal rats with HIBD.Application of BACE1 inhibitor can reduce the expression of Aβ,increase the expression of Bcl-2,and alleviate neuronal apoptosis.

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备注/Memo

备注/Memo:
基金项目:北京市教育委员会科技计划、社科计划项目(KM201910025001); 出生缺陷与相关妇儿疾病教育部重点实验室开放基金资助项目(2022KF04)
更新日期/Last Update: 2024-04-07