Fuzhou General Hospital of Nanjing Military Command, Fuzhou, Fujian 350025, P.R. China.
Int J Mol Med. 2012 Jul;30(1):119-25. doi: 10.3892/ijmm.2012.955. Epub 2012 Apr 2.
Diabetic nephropathy (DN), which is characterized by mesangial cell proliferation, is a common complication observed in diabetic patients. The protective effects of quercetin for DN have been reported; however, the mechanism has yet to be determined. We aimed to identify the underlying mechanism for quercetin protection against DN. High glucose (HG)-induced human mesangial cell (HMC) proliferation, a feature of the early stages of diabetic nephropathy, was employed as an in vitro model. Cells were grown in normal glucose (5.6 mM), high glucose (30 mM) or high glucose with various concentrations of quercetin. Cell proliferation, cell cycle progression, and expression of NF-κB and MCP-1 were examined by MTT assay, DNA staining, immunocytochemistry and western blot analysis, respectively. HMCs cultured in high glucose had signficantly greater proliferation, accumulation in the G1 phase, upregulated NF-κB and MCP-1 expression. Quercetin treatment reversed the effects of high glucose in a dose-dependent manner. Cotreatment of quercetin with pyrrolidine dithiocarbamate (PDTC), an inhibitor of NF-κB activation, suggest that the effects of quercetin are partially mediated by NF-κB signaling. Quercetin partially suppresses the effects of high glucose in HMC cultures, which are mediated at least in part through the suppression of NF-κB.
糖尿病肾病 (DN) 以系膜细胞增殖为特征，是糖尿病患者常见的并发症。槲皮素对 DN 具有保护作用，但作用机制尚未确定。本研究旨在探讨槲皮素对 DN 的保护作用机制。高糖 (HG) 诱导的人肾小球系膜细胞 (HMC) 增殖是糖尿病肾病早期的特征，被用作体外模型。细胞在正常葡萄糖 (5.6mM)、高葡萄糖 (30mM) 或高葡萄糖加不同浓度槲皮素中培养。通过 MTT 法检测细胞增殖、细胞周期进程，免疫细胞化学和 Western blot 分析分别检测 NF-κB 和 MCP-1 的表达。高糖培养的 HMC 增殖明显增加，G1 期积累增加，NF-κB 和 MCP-1 表达上调。槲皮素处理以剂量依赖的方式逆转高葡萄糖的作用。槲皮素与吡咯烷二硫代氨基甲酸盐 (PDTC) 共同处理，NF-κB 激活抑制剂，表明槲皮素的作用部分通过 NF-κB 信号转导介导。槲皮素部分抑制 HMC 培养物中高葡萄糖的作用，至少部分通过抑制 NF-κB 来实现。
