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SNP-9对Aβ25-35导致bEnd.3细胞损伤的作用及其机制

孟悦, 姚思远, 高向东, 陈松

孟悦, 姚思远, 高向东, 陈松. SNP-9对Aβ25-35导致bEnd.3细胞损伤的作用及其机制[J]. 中国药科大学学报, 2022, 53(3): 333-339. DOI: 10.11665/j.issn.1000-5048.20220311
引用本文: 孟悦, 姚思远, 高向东, 陈松. SNP-9对Aβ25-35导致bEnd.3细胞损伤的作用及其机制[J]. 中国药科大学学报, 2022, 53(3): 333-339. DOI: 10.11665/j.issn.1000-5048.20220311
MENG Yue, YAO Siyuan, GAO Xiangdong, CHEN Song. Effects and mechanisms of SNP-9 on Aβ25-35-induced damage in bEnd.3 cells[J]. Journal of China Pharmaceutical University, 2022, 53(3): 333-339. DOI: 10.11665/j.issn.1000-5048.20220311
Citation: MENG Yue, YAO Siyuan, GAO Xiangdong, CHEN Song. Effects and mechanisms of SNP-9 on Aβ25-35-induced damage in bEnd.3 cells[J]. Journal of China Pharmaceutical University, 2022, 53(3): 333-339. DOI: 10.11665/j.issn.1000-5048.20220311

SNP-9对Aβ25-35导致bEnd.3细胞损伤的作用及其机制

基金项目: 国家自然科学基金资助项目(No.82073755;No.82173728;No.81872850)

Effects and mechanisms of SNP-9 on Aβ25-35-induced damage in bEnd.3 cells

Funds: This study was supported by the National Natural Science Foundation of China (No.82073755, No.82173728, No.81872850)
  • 摘要: 为了研究来源于丝素蛋白水解物的神经保护活性多肽SNP-9对于阿尔茨海默病(Alzheimer′s disease,AD)中血脑屏障损伤的作用,使用Aβ25-35损伤脑微血管内皮细胞bEnd.3建立AD损伤模型,并给药干预。通过MTT实验检测SNP-9和Aβ25-35对细胞活力的影响;RT-qPCR法检测SNP-9和Aβ25-35对细胞紧密连接(tight junctions,TJs)相关的ZO-1、occludin和claudin-5 mRNA水平的影响;Western blot检测SNP-9和Aβ25-35对细胞TNF-α、磷酸化NF-κB、NF-κB、IκBα和RAGE蛋白水平的影响。实验结果显示,SNP-9给药减少了Aβ25-35诱导的bEnd.3细胞损伤,改善了模型细胞中ZO-1、occludin和claudin-5 mRNA水平的异常情况,缓解了Aβ25-35导致的TNF-α、磷酸化NF-κB、IκBα和RAGE蛋白水平异常。研究结果表明,SNP-9可能通过影响RAGE/NF-κB通路,调控模型细胞炎症因子TNF-α水平,改善TJs相关指标异常,缓解Aβ25-35诱导的bEnd.3细胞损伤。
    Abstract: In order to investigate the effects of neuroprotective peptide SNP-9 which is derived from silk fibroin hydrolysate on the injury of the blood-brain barrier in Alzheimer′s disease (AD), Aβ25-35 was used to damage brain microvascular endothelial cells bEnd.3 to establish AD injury model and drug intervention was performed.MTT assay was used to detect the effects of SNP-9 and Aβ25-35 on cell viability.RT-qPCR was used to determine the effects of SNP-9 and Aβ25-35 on the mRNA levels of tight junctions (TJs)-related ZO-1, occludin and claudin-5.Western blot was used to detect the effects of SNP-9 and Aβ25-35 on the protein levels of TNF-α, phosphorylated NF-κB, NF-κB, IκBα and RAGE.The results showed that SNP-9 reduced bEnd.3 cell damage induced by Aβ25-35, and improved the abnormal mRNA levels of ZO-1, occludin and claudin-5 in model cells.It alleviated the abnormal protein levels of TNF-α, phosphorylated NF-κB, IκBα and RAGE induced by Aβ25-35. These results suggest that SNP-9 may regulate the levels of TNF-α in model cells by influencing RAGE/NF-κB pathway, and then ameliorate TJs-related abnormalities and alleviate bEnd.3 cell injury induced by Aβ25-35.
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出版历程
  • 收稿日期:  2022-01-18
  • 修回日期:  2022-05-10
  • 刊出日期:  2022-06-24

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