Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalai Nagar-608 002, Tamil Nadu, India.
Eur J Pharmacol. 2011 Sep 30;667(1-3):355-64. doi: 10.1016/j.ejphar.2011.06.011. Epub 2011 Jun 17.
The study determines the effect of genistein on inflammatory status and expression of nuclear factor-kappa B (NF-κB p65), transforming growth factor-β1 (TGF-β1) and receptor for advanced glycation end products (RAGE) in kidney of fructose-fed rats. Adult male Wistar rats were fed a diet containing either starch or fructose as the source of carbohydrate. Fifteen days later, after confirming the development of insulin resistance in fructose-fed rats, the rats in each dietary group were divided into two and treated with either genistein (1 mg/kg/day) in 30% dimethylsulfoxide (DMSO) or 30% DMSO alone for the next 45 days. The expression of NF-κB P(65), TGF-β1 and RAGE, histochemical localization of α-smooth muscle actin (α-SMA), levels of tumour necrosis factor-α (TNF-α) and interleukin-6(IL-6) and ultrastructural analysis were performed at the end of the experimental period. Fructose-fed rats displayed inflammatory changes in kidney. Increased expression of TGF-β1 and RAGE in cytosol and NF-κB p65 in nuclear fraction were observed. α-SMA expression was higher in fructose-fed rat kidney. Proliferation of connective tissue was evident from increased collagen deposition in perivascular and intraglomerular regions. Administration of genistein to fructose-fed rats reduced inflammation, fibrogenesis and NF-κB activation. Genistein also mitigated the structural changes such as basement membrane thickening, reduction in podocyte number and loss of glomerular filtration barrier integrity. These findings suggest that genistein prevents inflammation, fibrosis and early nephropathic changes in fructose-fed insulin resistant rats secondary to the attenuation of NF-κB activation.
该研究旨在确定染料木黄酮对果糖喂养大鼠肾脏中炎症状态以及核因子-κB（NF-κB p65）、转化生长因子-β1（TGF-β1）和晚期糖基化终产物受体（RAGE）表达的影响。成年雄性 Wistar 大鼠喂食含淀粉或果糖作为碳水化合物来源的饮食。15 天后，在确认果糖喂养大鼠发生胰岛素抵抗后，将每组饮食中的大鼠分为两组，分别用 30%二甲亚砜（DMSO）中的染料木黄酮（1mg/kg/天）或单独的 30%DMSO 处理 45 天。实验结束时，检测 NF-κB P(65)、TGF-β1 和 RAGE 的表达、α-平滑肌肌动蛋白（α-SMA）的组织化学定位、肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）的水平以及超微结构分析。果糖喂养的大鼠肾脏出现炎症变化。细胞质中 TGF-β1 和 RAGE 的表达增加，核部分的 NF-κB p65 表达增加。α-SMA 在果糖喂养大鼠的肾脏中表达更高。肾小球内和血管周围区域胶原沉积增加，表明结缔组织增生。给予染料木黄酮可减少果糖喂养大鼠的炎症、纤维化和 NF-κB 激活。染料木黄酮还减轻了结构变化，如基底膜增厚、足细胞数量减少和肾小球滤过屏障完整性丧失。这些发现表明，染料木黄酮通过抑制 NF-κB 激活，预防果糖喂养的胰岛素抵抗大鼠的炎症、纤维化和早期肾病变化。
