Yonsei University College of Medicine, Department of Internal Medicine, 134 Shinchon-Dong, Seodaemoon-Gu, Seoul, South Korea.
Nephrol Dial Transplant. 2010 Jul;25(7):2134-41. doi: 10.1093/ndt/gfq063. Epub 2010 Feb 15.
Previous studies have demonstrated that AST-120 (Kremezin((R))), a well-known oral adsorbent, inhibits the progression of diabetic (DM) and non-DM chronic kidney disease along with a decrease in oxidative stress. This study was undertaken to investigate whether AST-120 could reduce oxidative stress and ameliorate the development of nephropathy in experimental DM rats with normal renal function.
Rats were injected with diluent (C, n = 16) or 65 mg/kg streptozotocin intraperitoneally (DM, n = 16), and eight rats from each group were treated with chow containing 5% AST-120. After 3 months, plasma advanced oxidation protein products (AOPP) and total malondialdehyde (MDA) levels, 24-h urinary albumin excretion, and urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) excretion were determined by ELISA. Glomerular endothelial nitric oxide synthase (eNOS), subunits of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (gp91phox, p47phox and p22phox), and fibronectin (FN) mRNA and protein expressions were determined by real-time PCR and western blot, respectively. In addition, dichlorodihydrofluorescein diacetate (DCF-DA) staining was performed to detect glomerular reactive oxygen species (ROS) production.
Compared to the C group, 24-h urinary albumin excretion was significantly higher in the DM group (P < 0.01), and AST-120 treatment significantly reduced albuminuria in DM rats (P < 0.05). Glomerular eNOS, gp91phox, p47phox and FN expression were significantly increased in DM rats compared to C rats, and these increases in DM glomeruli were significantly abrogated by AST-120 treatment (P < 0.05). The increases in plasma AOPP and MDA levels as well as renal oxidative stress in DM rats, assessed by DCF-DA staining and urinary 8-OHdG excretion rates, were also significantly attenuated by AST-120 treatment (P < 0.05).
In conclusion, the renoprotective effects of AST-120 in DM nephropathy seem to be associated with the amelioration of enhanced oxidative stress and FN expression under diabetic conditions.
先前的研究表明，AST-120（Kremezin((R))），一种知名的口服吸附剂，可抑制糖尿病（DM）和非 DM 慢性肾病的进展，同时降低氧化应激。本研究旨在探讨 AST-120 是否可降低氧化应激并改善肾功能正常的实验性 DM 大鼠的肾病发展。
大鼠腹腔内注射稀释剂（C 组，n = 16）或 65mg/kg 链脲佐菌素（DM 组，n = 16），每组 8 只大鼠给予含 5% AST-120 的普通饲料。3 个月后，通过 ELISA 测定血浆晚期氧化蛋白产物（AOPP）和总丙二醛（MDA）水平、24 小时尿白蛋白排泄量和尿 8-羟基-2'-脱氧鸟苷（8-OHdG）排泄量。实时 PCR 和 Western blot 分别测定肾小球内皮型一氧化氮合酶（eNOS）、烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶亚基（gp91phox、p47phox 和 p22phox）和纤维连接蛋白（FN）mRNA 和蛋白表达。此外，通过二氯二氢荧光素二乙酸酯（DCF-DA）染色检测肾小球活性氧（ROS）产生。
与 C 组相比，DM 组 24 小时尿白蛋白排泄量明显升高（P < 0.01），AST-120 治疗可显著降低 DM 大鼠的蛋白尿（P < 0.05）。与 C 组大鼠相比，DM 组大鼠肾小球 eNOS、gp91phox、p47phox 和 FN 表达明显增加，AST-120 治疗明显减弱了 DM 肾小球的这些增加（P < 0.05）。DM 大鼠的血浆 AOPP 和 MDA 水平升高以及肾脏氧化应激，通过 DCF-DA 染色和尿 8-OHdG 排泄率评估，也被 AST-120 治疗显著减弱（P < 0.05）。
总之，AST-120 在 DM 肾病中的肾脏保护作用似乎与改善糖尿病条件下增强的氧化应激和 FN 表达有关。
