Chengdu Medical College, Chengdu Sichuan 610500, China.
Department of Critical Care Medicine, The First Affiliated Hospital of Chengdu Medical College, Chengdu Sichuan 610500, China.
Comput Math Methods Med. 2022 Sep 8;2022:1949344. doi: 10.1155/2022/1949344. eCollection 2022.
Alzheimer's disease (AD) is the most commonly seen neurodegenerative brain disorder. The paracrine effects of mesenchymal stem cells (MSCs) signify to trigger immunomodulation and neural regeneration. However, the role and mechanism of bone marrow MSC- (BMSC-) derived CX3CL1 in AD remains elusive. In this study, A -intervened SH-SY5Y cells were used for AD cell model construction. pcDNA-ligated CX3CL1 overexpression plasmids were transfected into BMSCs. The levels of soluble and membrane-bound CX3CL1 were detected by ELISA and Western blotting (WB), respectively. The growth, apoptosis, and pathology of AD model cells were evaluated by CCK-8, flow cytometry, immunofluorescence, morphology observation, biochemical examination, and WB. It was found that A significantly reduced CX3CL1 expression either in soluble or membrane-bound form, cell viability, relative protein expression of synaptic markers, SOD, CAT, and GSH-Px contents, as well as Trx protein expression; in addition, it enhanced the apoptosis rate, the relative expression of cleaved caspase-3, A, tau, p-Tau, Iba1, MDA, TXNIP, and NLRP3 in SH-SY5Y cells; however, the above effects were prominently reversed by the coculture of BMSCs. Moreover, overexpression of CX3CL1 in BMSCs observably strengthened the corresponding tendency caused by BMSCs. In conclusion, through the TXNIP/NLRP3 pathway, CX3CL1 derived from BMSCs inhibited pathological damage in A -induced SH-SY5Y.
阿尔茨海默病（AD）是最常见的神经退行性脑疾病。间充质干细胞（MSCs）的旁分泌作用表明可以触发免疫调节和神经再生。然而，骨髓间充质干细胞（BMSC）衍生的 CX3CL1 在 AD 中的作用和机制仍不清楚。在本研究中，使用 A 干预的 SH-SY5Y 细胞构建 AD 细胞模型。将 pcDNA 连接的 CX3CL1 过表达质粒转染到 BMSCs 中。通过 ELISA 和 Western blot（WB）分别检测可溶性和膜结合型 CX3CL1 的水平。通过 CCK-8、流式细胞术、免疫荧光、形态观察、生化检查和 WB 评估 AD 模型细胞的生长、凋亡和病理学。结果发现，A 以可溶性或膜结合形式显著降低 CX3CL1 的表达、细胞活力、突触标志物的相对蛋白表达、SOD、CAT 和 GSH-Px 含量以及 Trx 蛋白表达；此外，它还增强了细胞凋亡率、裂解型 caspase-3、A、tau、p-Tau、Iba1、MDA、TXNIP 和 NLRP3 在 SH-SY5Y 细胞中的相对表达；然而，BMSCs 的共培养显著逆转了上述效应。此外，BMSCs 中 CX3CL1 的过表达明显增强了 BMSCs 引起的相应趋势。综上所述，通过 TXNIP/NLRP3 通路，BMSCs 衍生的 CX3CL1 抑制了 A 诱导的 SH-SY5Y 中的病理损伤。
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