Internal medicine department of Hebei Medical University Shijiazhuang, Hebei, PR China.
Kidney Blood Press Res. 2012;36(1):85-97. doi: 10.1159/000341485. Epub 2012 Aug 27.
Recent studies indicate farnesoid X receptor (FXR) plays an important role in regulating lipid metabolism in kidney disease. The purpose of the present study is to investigate the effect of chenodeoxycholic acid (CDCA), a FXR agonist, on fibrosis, inflammation and oxidative stress in kidney in rats fed on high fructose.
Twenty-four healthy male Wistar rats were randomly divided into three groups (n=8): normal control group, high fructose group and chenodeoxycholic acid group. Rats were sacrificed by the end of 16 weeks after feeding. Blood urea nitrogen, serum creatinine, fast glucose, lipid concentration were observed, spot urine samples were obtained to measure the albumin and creatinine levels. Triglyceride of renal cortices was detected. The mRNA level and protein contents of the fibrosis-inducing growth factor transforming growth factor β1 (TGF-β1) and plasminogen activator inhibitor (PAI-I), inflammatory cytokines tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6), oxidative stress index NADPH oxidase 2 (Nox2) and p22phox in kidney were examined. The pathological changes of kidney were examined by PAS staining and immunohistochemical staining. Electron microscope sections were made to measure glomerular basement membrane (GBM) width.
Renal injuries including mesangial expansion, GBM thickness and podocyte foot process effacement were found in fructose-fed Wistar rats, FXR agonist CDCA modulates renal lipid metabolism, decreases proteinuria and improves renal fibrosis, inflammation and oxidation stress. High-fructose-feeding may cause lipid nephrotoxicity through down-regulated farnesoid X receptor and increases expression of profibrotic growth factors, proinflammatory cytokines, and oxidative stress in Wistar rats.
FXR activation by chenodeoxycholic acid can prevent the injury in kidney induced by high fructose feeding.
最近的研究表明法尼醇 X 受体（FXR）在肾脏疾病的脂质代谢调节中发挥重要作用。本研究旨在探讨 FXR 激动剂鹅去氧胆酸（CDCA）对高果糖喂养大鼠肾脏纤维化、炎症和氧化应激的影响。
将 24 只健康雄性 Wistar 大鼠随机分为三组（n=8）：正常对照组、高果糖组和鹅去氧胆酸组。喂养 16 周后处死大鼠。观察血尿素氮、血清肌酐、空腹血糖、血脂浓度，留取尿标本检测白蛋白和肌酐水平。检测肾皮质甘油三酯。检测纤维化诱导生长因子转化生长因子 β1（TGF-β1）和纤溶酶原激活物抑制剂（PAI-I）、炎症细胞因子肿瘤坏死因子 α（TNF-α）和白细胞介素 6（IL-6）、氧化应激指标 NADPH 氧化酶 2（Nox2）和 p22phox 的 mRNA 水平和蛋白含量。通过 PAS 染色和免疫组织化学染色观察肾脏的病理变化。制作电镜切片测量肾小球基底膜（GBM）宽度。
果糖喂养的 Wistar 大鼠出现系膜扩张、GBM 增厚和足细胞足突消失等肾损伤，FXR 激动剂 CDCA 可调节肾脏脂质代谢，减少蛋白尿，改善肾纤维化、炎症和氧化应激。高果糖喂养可能通过下调法尼醇 X 受体增加致纤维化生长因子、促炎细胞因子和氧化应激的表达，导致脂质肾毒性。
鹅去氧胆酸激活 FXR 可预防高果糖喂养引起的肾脏损伤。
