de Assis Adriano M, Rech Anderson, Longoni Aline, da Silva Morrone Maurílio, de Bittencourt Pasquali Matheus A, Perry Marcos L S, Souza Diogo O, Moreira José C F
Postgraduate Program in Biochemistry, ICBS, Federal University of Rio Grande do Sul, Porto Alegre, RS 90035-003, Brazil; Department of Biochemistry, Federal University of Rio Grande do Sul, Porto Alegre, RS 90035-003, Brazil.
Postgraduate Program in Biochemistry, ICBS, Federal University of Rio Grande do Sul, Porto Alegre, RS 90035-003, Brazil.
Nutr Res. 2015 Jun;35(6):512-22. doi: 10.1016/j.nutres.2015.04.013. Epub 2015 Apr 25.
Renal dysfunction is a severe complication that is caused by diabetes mellitus. Many factors associate the progression of this complication with high levels of proinflammatory and pro-oxidant substances, such as advanced glycation end products (AGEs), which form a heterogeneous group of compounds that can accumulate in tissues such as retinas, joints, and kidneys. The hypothesis of this study is that n-3 polyunsaturated fatty acids (n-3 PUFAs) have a nephroprotective effect on rats after exposing them to a combination of 2 protocols that increase the AGE amounts: a high-fat diet enriched with AGEs and a diabetes rat model. Adult Wistar rats were divided into 6 groups that received the following diets for 4 weeks: (1) control group; 2) HAGE: high AGE fat-containing diet group; (3) HAGE + n-3: high AGE fat-containing diet plus n-3 PUFAs group; (4) diabetic group; (5) Db + HAGE: high AGE fat-containing diet diabetic group; and (6) Db + HAGE + n-3: high AGE fat-containing diet plus n-3 PUFAs diabetic group. Diabetes mellitus was induced by an intraperitoneal injection of alloxan (150 mg kg(-1)). In diabetic and nondiabetic rats, the high HAGE fat-containing diet increased the serum creatinine, tumor necrosis factor-α, thiobarbituric acid reactive substances, and reactive oxygen species levels, as well as the superoxide dismutase/catalase + glutathione peroxidase ratio and the superoxide dismutase 2 and receptor for advanced glycation end products immunocontent of the kidneys. n-3 Polyunsaturated fatty acids attenuated these alterations and influenced the receptor for advanced glycation end products/oxidative stress/tumor necrosis factor-α axis. In summary, this study showed that the extrinsic AGE pathway (HAGE diet) had a greater effect on renal metabolism than the intrinsic AGE pathway (diabetes induction) and that n-3 PUFAs appear to prevent renal dysfunction via antioxidant and anti-inflammatory pathways.
肾功能障碍是糖尿病引发的一种严重并发症。许多因素将这种并发症的进展与高水平的促炎和促氧化物质联系起来，比如晚期糖基化终末产物（AGEs），它们是一类异质性化合物，可在视网膜、关节和肾脏等组织中蓄积。本研究的假设是，n-3多不饱和脂肪酸（n-3 PUFAs）在将大鼠暴露于两种增加AGE量的方案组合后，对大鼠具有肾脏保护作用：富含AGE的高脂饮食和糖尿病大鼠模型。成年Wistar大鼠被分为6组，接受以下饮食4周：（1）对照组；（2）HAGE：富含AGE的高脂饮食组；（3）HAGE + n-3：富含AGE的高脂饮食加n-3 PUFAs组；（4）糖尿病组；（5）Db + HAGE：富含AGE的高脂饮食糖尿病组；（6）Db + HAGE + n-3：富含AGE的高脂饮食加n-3 PUFAs糖尿病组。通过腹腔注射四氧嘧啶（150 mg kg(-1)）诱导糖尿病。在糖尿病和非糖尿病大鼠中，富含HAGE的高脂饮食增加了血清肌酐、肿瘤坏死因子-α、硫代巴比妥酸反应性物质和活性氧水平，以及肾脏中超氧化物歧化酶/过氧化氢酶 + 谷胱甘肽过氧化物酶比值和超氧化物歧化酶2及晚期糖基化终末产物受体的免疫含量。n-3多不饱和脂肪酸减轻了这些改变，并影响晚期糖基化终末产物受体/氧化应激/肿瘤坏死因子-α轴。总之，本研究表明，外源性AGE途径（HAGE饮食）对肾脏代谢的影响大于内源性AGE途径（糖尿病诱导），并且n-3 PUFAs似乎通过抗氧化和抗炎途径预防肾功能障碍。
