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p53/microRNA-22 对蛛网膜下腔出血的神经保护作用调控炎症和细胞凋亡。

Neuroprotective effects of p53/microRNA‑22 regulate inflammation and apoptosis in subarachnoid hemorrhage.

机构信息

Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China.

出版信息

Int J Mol Med. 2018 Apr;41(4):2406-2412. doi: 10.3892/ijmm.2018.3392. Epub 2018 Jan 16.

Abstract

The present study aimed to investigate whether the neuroprotective effects of p53/microRNA‑22 regulate inflammation and apoptosis in subarachnoid hemorrhage (SAH). In a mouse model of SAH, microRNA‑22 expression was upregulated. In addition, downregulation of microRNA‑22 in HEB cells increased the mRNA expression levels of interleukin (IL)‑6, induced cysteine rich angiogenic inducer 61 (Cyr61) expression, and suppressed the protein expression levels of B‑cell lymphoma 2‑associated X protein (Bax) and caspase‑3 activity. Treatment with the p53 inhibitor, pifithrin‑α, suppressed p53 protein expression, increased IL‑6 mRNA expression, decreased microRNA‑22 expression, Bax protein expression and caspase‑3 activity, and induced Cyr61 expression in mice with SAH. Furthermore, p53 expression was knocked down using p53 small interfering RNA, which suppressed microRNA‑22 expression and increased IL‑6 mRNA expression, inhibited Bax protein expression and caspase‑3 activity, and induced Cyr61 expression in HEB cells. The present study demonstrated that the neuroprotective effects of p53/microRNA‑22 may regulate inflammation and apoptosis in SAH. Reverse transcription quantitative polymerase chain reaction (qPCR) was used to analyze the expression of microRNA-22, western blot analysis was used to analyze the protein expression of Bax and Cyr61.

摘要

本研究旨在探讨 p53/微小 RNA-22 是否通过调节炎症和细胞凋亡对蛛网膜下腔出血 (SAH) 发挥神经保护作用。在 SAH 小鼠模型中,miR-22 的表达上调。此外,在 HEB 细胞中下调 miR-22 可增加白细胞介素 (IL)-6mRNA 的表达,诱导胱氨酸丰富血管生成诱导因子 61 (Cyr61) 的表达,并抑制 B 细胞淋巴瘤 2 相关 X 蛋白 (Bax) 的蛋白表达和半胱天冬酶-3 活性。用 p53 抑制剂 pifithrin-α 处理可抑制 p53 蛋白表达,增加 IL-6mRNA 的表达,降低 miR-22 的表达,Bax 蛋白表达和半胱天冬酶-3 活性,并诱导 SAH 小鼠 Cyr61 的表达。此外,用 p53 小干扰 RNA 敲低 p53 表达,可抑制 miR-22 的表达并增加 IL-6mRNA 的表达,抑制 Bax 蛋白表达和半胱天冬酶-3 活性,并诱导 HEB 细胞 Cyr61 的表达。本研究表明,p53/微小 RNA-22 的神经保护作用可能通过调节 SAH 中的炎症和细胞凋亡发挥作用。逆转录定量聚合酶链反应 (qPCR) 用于分析 miR-22 的表达,Western blot 分析用于分析 Bax 和 Cyr61 的蛋白表达。

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