Ebenezer Philip J, Mariappan Nithya, Elks Carrie M, Haque Masudul, Soltani Zohreh, Reisin Efrain, Francis Joseph
Department of Comparative Biomedical Sciences, Louisiana State University School of Veterinary Medicine, Baton Rouge, LA 70803, USA.
Life Sci. 2009 Aug 26;85(9-10):357-64. doi: 10.1016/j.lfs.2009.06.019. Epub 2009 Jul 23.
We investigated the effects of the nuclear factor kappa B (NFkappaB) blocker pyrrolidine dithiocarbamate (PDTC) on high-fat diet (HFD)-induced metabolic and renal alterations in obese and lean Zucker rats (OZR and LZR, respectively).
Rats were fed a HFD resembling the typical "Western" diet or a regular diet (RD) and allowed free access to tap water or tap water containing PDTC (150 mg/kg body weight) for 10 weeks; rats were then sacrificed. Total ROS production rates were measured using electron paramagnetic resonance spectroscopy, and superoxide production was measured with lucigenin assay. Blood, plasma, and urine were analyzed. Semi-quantitative reverse transcriptase-polymerase chain reaction and electrophoretic mobility shift assay were conducted to assess NFkappaB mRNA levels and DNA binding activities, respectively; immunofluorescence was performed to assess protein levels.
OZR-HFD rats exhibited significantly higher levels of total renal cortical reactive oxygen species production, plasma lipids, insulin, C-reactive protein, blood urea nitrogen, creatinine, and urinary albumin excretion than all other groups (p<0.05); these changes were accompanied by a significant decrease in plasma high density lipoprotein levels (p<0.05). Gene expression levels of desmin, cytokine and oxidative stress genes were significantly higher in the renal cortical tissues of OZR-HFD; NFkappaB p65 DNA binding activity was also significantly higher in these animals. PDTC attenuated these changes.
Our data suggest that NFkappaB blockade may prove beneficial in treating the nephropathy often associated with metabolic syndrome.
我们研究了核因子κB（NFκB）阻滞剂吡咯烷二硫代氨基甲酸盐（PDTC）对高脂饮食（HFD）诱导的肥胖和瘦素 Zucker 大鼠（分别为 OZR 和 LZR）代谢及肾脏改变的影响。
给大鼠喂食类似典型“西方”饮食的高脂饮食或常规饮食（RD），并让它们自由饮用自来水或含 PDTC（150 毫克/千克体重）的自来水，持续 10 周；然后处死大鼠。使用电子顺磁共振光谱法测量总活性氧生成率，用光泽精测定法测量超氧化物生成。对血液、血浆和尿液进行分析。分别进行半定量逆转录聚合酶链反应和电泳迁移率变动分析以评估 NFκB mRNA 水平和 DNA 结合活性；进行免疫荧光以评估蛋白水平。
与所有其他组相比，OZR-HFD 大鼠的肾皮质总活性氧生成、血浆脂质、胰岛素、C 反应蛋白、血尿素氮、肌酐和尿白蛋白排泄水平显著更高（p<0.05）；这些变化伴随着血浆高密度脂蛋白水平显著降低（p<0.05）。结蛋白、细胞因子和氧化应激基因的基因表达水平在 OZR-HFD 的肾皮质组织中显著更高；这些动物的 NFκB p65 DNA 结合活性也显著更高。PDTC 减轻了这些变化。
我们的数据表明，NFκB 阻断可能对治疗常与代谢综合征相关的肾病有益。
