Notch1信号通路相关蛋白在急性期缺氧缺血脑损伤SD乳鼠脑组织中表达变化及其对神经细胞凋亡的作用OACSTPCD
Expression changes of Notch1 signaling pathway-related proteins in brain tissues of immature SD rats with acute hypoxic-ischemic brain injury and their effect on neuronal apoptosis
目的 观察急性期缺氧缺血脑损伤SD乳鼠脑组织中Notch1信号通路相关蛋白(转录因子Notch1和其活性成分NICD以及其下游的蛋白HES1)表达变化及Notch1信号通路抑制后急性期缺氧缺血脑损伤SD乳鼠脑组织中神经细胞凋亡情况,以探讨Notch1信号通路在新生儿脑损伤中的作用及机制.方法 18只3日龄SD乳鼠随机分成Notch1抑制组、模型组及对照组,均分为6只.Notch1抑制组于造模前30 min腹腔注射DAPT(100 mg/kg),然后缺血缺氧处理;模型组缺氧和缺血处理前腹腔注射1%DMSO;对照组接受假手术.采用Western blottting法检测各组Notch1信号通路蛋白(Notch1、NICD、HES1)及凋亡蛋白(Caspas-3、Bax、Bcl-2);通过尼氏染色和TUNEL染色观察脑组织结构变化和细胞凋亡情况.结果 与对照组相比,模型组Notch1信号通路的转录因子NICD以及下游的调控蛋白HES1相对表达量升高(P均<0.05),促凋亡蛋白Caspas-3相对表达量升高(P<0.05),抗凋亡蛋白Bcl-2表达减少(P<0.05);与模型组相比,Notch1抑制组NICD和HES1蛋白相对表达量降低(P均<0.05),Caspas-3蛋白相对表达量降低(P<0.05),而Bcl-2相对表达量升高(P<0.05);与模型组比较,Notch1抑制组缺氧缺血损伤的脑组织结构明显改善,细胞凋亡数减少(P<0.05).结论 急性期缺氧缺血脑损伤SD乳鼠脑组织Notch1信号通路相关蛋白NICD、HES1升高,促凋亡蛋白Caspas-3表达增加、抗凋亡蛋白Bcl-2表达减少;Notch1信号通路抑制后,急性期缺氧缺血脑损伤SD乳鼠脑组织中神经细胞凋亡减少;Notch1信号通路可通过促进脑组织中神经细胞凋亡从而诱发新生儿脑损伤.
Objective To observe the expression changes of Notch1 signaling pathway-related proteins(transcrip-tion factor notch1,NICD,and its downstream protein HES1),and the apoptosis of neurons after inhibition of Notch1 sig-naling pathway in brain tissues of immature SD rats with acute hypoxic-ischemic brain injury,so as to investigate the role and mechanism of Notch1 signaling pathway in neonatal brain injury.Methods Eighteen three-day-old Sprague-Dawley rats were randomly divided into the Notch1 inhibition group,model group,and control group(6 rats),respectively.Rats in the Notch1 inhibition group were intraperitoneally injected with DAPT(100 mg/kg)30 min before modeling,and then were treated with ischemia and hypoxia.Rats in the model group were intraperitoneally injected with 1%DMSO before hy-poxia and ischemia treatment.Rats in the control group received sham surgery.Notch1 signaling pathway proteins(notch1,NICD,and HES1)and apoptotic proteins(Caspas-3,Bax,and Bcl-2)were detected by Western blotting.The changes of brain structure and apoptosis were observed by Niss staining and TUNEL staining.Results Compared with the control group,the expression levels of transcription factor NICD of Notch1 signaling pathway and its downstream regula-tory protein HES1 increased(both P<0.05),the expression level of pro-apoptotic protein Caspas-3 increased(P<0.05),and the expression level of anti-apoptotic protein Bcl-2 decreased in the model group(P<0.05).Compared with the model group,the expression levels of NICD and HES1 protein decreased(both P<0.05),the expression level of Caspas-3 pro-tein decreased(P<0.05),and the expression level of Bcl-2 increased in the Notch1 inhibition group(P<0.05).Com-pared with the model group,the brain tissue structure of the Notch1 inhibition group was significantly improved and the number of apoptotic neurons decreased(both P<0.05).Conclusions Notch1 signaling pathway-related proteins NICD and HES1 increased,the expression of pro-apoptotic protein Caspase-3 increased,and the expression of anti-apoptotic pro-tein Bcl-2 decreased in SD rats with acute hypoxic-ischemic brain injury.After the inhibition of Notch1 signaling pathway,the apoptosis of nerve cells decreased in SD rats with acute hypoxic-ischemic brain injury.Notch1 signaling pathway in-duced the neonatal brain injury by promoting nerve cell apoptosis in the brain tissues.
高力敏;李莎莎;高树强;单海蕾;郭春艳;赵宏伟;武彦秋
承德医学院附属医院新生儿科 河北省泛血管疾病重点实验室,河北承德 067000
临床医学
Notch1信号通路细胞凋亡缺氧缺血脑损伤早产儿脑损伤
Notch1 signaling pathwayapoptosishypoxic-ischemic brain injurypremature brain injury
《山东医药》 2024 (027)
31-34 / 4
河北省自然科学基金资助项目(241 H2022406039);河北省卫健委项目(20231401).
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