Objective. It has been shown that podocyte injury represents an important pathological basis that contributes to proteinuria and eventually leads to kidney failure. High glucose (HG) activates macrophage polarization, further exacerbating HG-induced podocyte injury. Our previous study on diabetic nephropathy rats indicated that thalidomide (Tha) has renoprotective properties. The present study explored the effects of Tha on mRNA and protein expressions of inducible nitric oxide synthase (iNOS), tumor necrosis factor- (TNF-) α, mannose receptor (CD206), and arginase- (Arg-) 1 in HG-activated macrophages. iNOS and TNF-α are established as markers of classically activated macrophage (M1). CD206 and Arg-1 are regarded as markers of alternatively activated macrophages (M2). During the experiment, the supernatants of (HG)-treated and (Tha)-treated macrophages, designated as (HG) MS and (Tha) MS, were simultaneously collected and processed. TNF-α and interleukin- (IL-) 1β levels as well as protein expressions of nephrin and podocin in HG, (HG) MS, and (Tha) MS-cultured podocytes were evaluated. The results showed that compared to the 11.1 mM normal glucose (NG), the 33.3 mM HG-cultured RAW 264.7 cells exhibited upregulated iNOS and TNF-α mRNAs and protein expressions, and downregulated CD206 and Arg-1 expressions significantly (). Tha 200 μg/ml suppressed iNOS and TNF-α, and promoted CD206 and Arg-1 expressions significantly compared to the HG group (). Furthermore, (HG) MS-treated podocytes showed an increase in TNF-α and IL-1β levels and a downregulation in nephrin and podocin expression significantly compared to NG-treated and HG-treated podocytes (). The (Tha 200 μg/ml) MS group exhibited a decrease in TNF-α and IL-1β level, and an upregulation in nephrin and podocin expressions significantly compared to the (HG) MS group (). Our research confirmed that HG-activated macrophage differentiation aggravates HG-induced podocyte injury in vitro and the protective effects of Tha might be related to its actions on TNF-α and IL-1β levels via its modulation on M1/M2 differentiation.

中文翻译：

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沙利度胺通过体外调节巨噬细胞 M1/M2 分化对高葡萄糖诱导的足细胞损伤的保护作用。

客观的。研究表明，足细胞损伤是导致蛋白尿并最终导致肾衰竭的重要病理基础。高葡萄糖 (HG) 激活巨噬细胞极化，进一步加剧 HG 诱导的足细胞损伤。我们之前对糖尿病肾病大鼠的研究表明沙利度胺（Tha）具有肾脏保护作用。本研究探讨了 Tha 对 HG 激活的诱导型一氧化氮合酶 (iNOS)、肿瘤坏死因子 (TNF-) α、甘露糖受体 (CD206) 和精氨酸酶 (Arg-) 1 的 mRNA和蛋白表达的影响巨噬细胞。iNOS 和 TNF- α被确立为经典活化巨噬细胞 (M1) 的标志物。CD206 和 Arg-1 被认为是替代激活巨噬细胞 (M2) 的标记。在实验过程中，同时收集和处理（HG）处理和（Tha）处理的巨噬细胞的上清液，指定为（HG）MS和（Tha）MS。评估了 HG、(HG) MS 和 (Tha) MS 培养的足细胞中的TNF- α和白细胞介素 (IL-) 1 β水平以及去氧肾上腺素和足多蛋白的蛋白表达。结果显示，与11.1 mM正常葡萄糖（NG）相比，33.3 mM HG培养的RAW 264.7细胞表现出iNOS和TNF- α mRNA和蛋白表达上调，并显着下调CD206和Arg-1表达。）。与 HG 组相比，Tha 200  μg /ml 抑制 iNOS 和 TNF- α ，并显着促进 CD206 和 Arg-1 表达（）。此外，与 NG 处理和 HG 处理的足细胞相比， (HG) MS 处理的足细胞显示 TNF- α和 IL-1 β水平增加）。与(HG) MS 组相比，(Tha 200  μg /ml) MS 组的 TNF- α和 IL-1 β水平显着降低，nephrin 和 podocin 表达显着上调。）。我们的研究证实，HG 激活的巨噬细胞分化在体外加重了 HG 诱导的足细胞损伤，Tha 的保护作用可能与其通过调节 M1/M2 分化而对 TNF- α和 IL-1 β水平的作用有关