Mxene-bpV 通过激活 Akt 和促进 M2 小胶质细胞极化信号通路,在脑缺血再灌注损伤中发挥神经保护作用。

IF 4.2 3区 医学 Q2 ENGINEERING, BIOMEDICAL
Jing Cheng, Han Yu, Zhi-Feng Zhang, Hong-Xiang Jiang, Ping Wu, Zhou-Guang Wang, Zhi-Biao Chen, Li-Quan Wu
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引用次数: 0

摘要

研究表明,抑制染色体10上缺失的磷酸酶和天丝同源物(PTEN)对缺血/再灌注(I/R)损伤具有神经保护作用。双过氧钒(bpV)是钒酸盐的一种衍生物,是一种成熟的 PTEN 抑制剂。然而,由于其穿透细胞膜的能力普遍不足,其功能受到了限制。Mxene(Ti3C2Tx)是一种新型二维片状纳米材料,具有极佳的穿透细胞膜的能力。然而,这种纳米材料对神经系统疾病的影响还有待进一步研究。本文首次利用 Mxene(Ti3C2Tx)携带 bpV(HOpic),创造出一种新型纳米复合材料 Mxene-bpV,并在脑 I/R 损伤模型中进行了研究。研究结果表明,这种人工合成的 Mxene-bpV 具有足够的稳定性,可以轻松穿过细胞膜。我们观察到,Mxene-bpV能显著提高小鼠脑I/R损伤后氧葡萄糖剥夺/再灌注(OGD/R)损伤神经元的存活率,缩小梗死面积,促进脑功能的恢复。最重要的是,在同一时期,Mxene-bpV治疗比单独使用bpV(HOpic)治疗更有效。从机理上讲,Mxene-bpV 可抑制 PTEN 在体外和体内的酶活性。它还通过抑制 PTEN 促进磷酸化-Akt(Ser473)的表达,然后激活 Akt 通路以提高细胞存活率。此外,在 PTEN 转基因小鼠中,Mxene-bpV 通过抑制 PTEN 促进 M2 小胶质细胞极化,从而抑制了 I/R 诱导的炎症反应。总之,纳米合成的 Mxene-bpV 通过激活 Akt 通路和促进 M2 小胶质细胞极化,抑制了 PTEN 的酶活性,最终发挥了对脑 I/R 损伤的神经保护作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Mxene-bpV plays a neuroprotective role in cerebral ischemia-reperfusion injury by activating the Akt and promoting the M2 microglial polarization signaling pathways

Mxene-bpV plays a neuroprotective role in cerebral ischemia-reperfusion injury by activating the Akt and promoting the M2 microglial polarization signaling pathways

Studies have shown that the inhibition of phosphatase and tensin homolog deleted on chromosome 10 (PTEN)was neuroprotective against ischemia/reperfusion(I/R) injury. Bisperoxovanadium (bpV), a derivative of vanadate, is a well-established inhibitor of PTEN. However, its function islimited due to its general inadequacy in penetrating cell membranes. Mxene(Ti3C2Tx) is a novel two-dimensional lamellar nanomaterial with an excellent ability to penetrate the cell membrane. Yet, the effects of this nanomaterial on nervous system diseases have yet to be scrutinized. Here, Mxene(Ti3C2Tx) was used for the first time to carry bpV(HOpic), creating a new nanocomposite Mxene-bpV that was probed in a cerebral I/R injury model. The findings showed that this synthetic Mxene-bpV was adequately stable and can cross the cell membraneeasily. We observed that Mxene-bpV treatment significantly increased the survival rate of oxygen glucose deprivation/reperfusion(OGD/R)--insulted neurons, reduced infarct sizes and promoted the recovery of brain function after mice cerebral I/R injury. Crucially, Mxene-bpV treatment was more therapeutically efficient than bpV(HOpic) treatment alone over the same period. Mechanistically, Mxene-bpV inhibited the enzyme activity of PTEN in vitro and in vivo. It also promoted the expression of phospho-Akt (Ser473) by repressing PTEN and then activated the Akt pathway to boost cell survival. Additionally, in PTEN transgenic mice, Mxene-bpV suppressed I/R-induced inflammatory response by promoting M2 microglial polarization through PTEN inhibition. Collectively, the nanosynthetic Mxene-bpV inhibited PTEN’ enzymatic activity by activating Akt pathway and promoting M2 microglial polarization, and finally exerted neuroprotection against cerebral I/R injury.

Graphical Abstract

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来源期刊
Journal of Materials Science: Materials in Medicine
Journal of Materials Science: Materials in Medicine 工程技术-材料科学:生物材料
CiteScore
8.00
自引率
0.00%
发文量
73
审稿时长
3.5 months
期刊介绍: The Journal of Materials Science: Materials in Medicine publishes refereed papers providing significant progress in the application of biomaterials and tissue engineering constructs as medical or dental implants, prostheses and devices. Coverage spans a wide range of topics from basic science to clinical applications, around the theme of materials in medicine and dentistry. The central element is the development of synthetic and natural materials used in orthopaedic, maxillofacial, cardiovascular, neurological, ophthalmic and dental applications. Special biomedical topics include biomaterial synthesis and characterisation, biocompatibility studies, nanomedicine, tissue engineering constructs and cell substrates, regenerative medicine, computer modelling and other advanced experimental methodologies.
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