Objective. The primary initiating mechanism in diabetes nephropathy (DN) is hyperglycemia-induced inflammation in which macrophage and podocyte play important roles. The present research is aimed at exploring the effects of kaempferol (Ka) and hydroxysafflor yellow A (HSYA) on classically activated (M1)/alternatively activated (M2) macrophage polarization and podocyte apoptosis under hyperglycaemic conditions in vitro. Methods. (1) RAW264.7 cells were treated with 11.1 mM glucose (NG), 33.3 mM glucose (HG), Ka 4–8 μM, and HSYA 100–200 μM separately. The expressions of inducible nitric oxide synthase (iNOS), tumor necrosis factor- (TNF-) α, mannose receptor (CD206), and arginase- (Arg-) 1 were quantified by Western blotting and real-time quantitative PCR. The collected supernatants from macrophage were named as (NG) MS, (HG) MS, (Ka) MS, and (HSYA) MS. (2) The podocyte survival rate was assessed by Bromodeoxyuridine assay, while TNF-α and interleukin- (IL-) 1β levels were evaluated by Elisa. Results. (1) Compared to the HG group, the Ka and HSYA 100 μM groups decreased iNOS and TNF-α levels and increased Arg-1 and CD206 expressions significantly (protein and mRNA: , respectively). (2) The podocyte survival rate of Ka 8 μM was higher than that of HG, and the rates of (Ka) MS and (HSYA 100 μM) MS were higher than that of (HG) MS significantly (all: ). (3) TNF-α and IL-1β levels of Ka and HSYA 100 μM were significantly lower than those of the HG group, and both levels in the (Ka) MS and (HSYA) MS were lower than those in the (HG) MS group significantly (, respectively). Conclusion. The protective effects of Ka and HSYA on podocyte apoptosis under hyperglycemic stress are related to their modulation on M1/M2 polarization and the lowering effects on TNF-α and IL-1β levels.

中文翻译：

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两种红花衍生化合物山奈酚和羟基红花黄 A 通过调节巨噬细胞 M1/M2 极化对高血糖应激诱导的足细胞凋亡的保护作用

客观。糖尿病肾病（DN）的主要起始机制是高血糖引起的炎症，其中巨噬细胞和足细胞发挥重要作用。本研究旨在探索山柰酚（Ka）和羟基红花黄A（HSYA）在体外高血糖条件下对经典活化（M1）/交替活化（M2）巨噬细胞极化和足细胞凋亡的影响。方法。(1) RAW264.7 细胞分别用 11.1 mM 葡萄糖 (NG)、33.3 mM 葡萄糖 (HG)、Ka 4–8  μM和 HYA 100–200  μM处理。诱导型一氧化氮合酶（iNOS）、肿瘤坏死因子-（TNF-）α的表达、甘露糖受体 (CD206) 和精氨酸酶- (Arg-) 1 通过蛋白质印迹和实时定量 PCR 进行定量。从巨噬细胞收集的上清液命名为(NG) MS、(HG) MS、(Ka) MS和(HSYA) MS。(2)足细胞存活率采用溴脱氧尿苷法测定，TNF -α和白细胞介素-(IL-) 1β水平采用Elisa法测定。结果。(1)与HG组相比，Ka和HSYA 100  μM组降低了iNOS和TNF - α的水平，显着增加了Arg-1和CD206的表达（蛋白和mRNA：，分别）。(2)Ka 8 μM足细胞存活率 高于HG，(Ka)MS和(HSYA  100μM )MS的存活率显着高于(HG)MS(均：）。(3)Ka和HSYA 100  μ M的TNF- α和IL- 1β水平显着低于HG组，且(Ka) MS和(HSYA) MS均低于( HG) MS 组显着 (，分别）。结论。Ka和HSYA对高血糖应激下足细胞凋亡的保护作用与其对M1/M2极化的调节以及对TNF - α和IL- 1β水平的降低作用有关。