Studies of renal injury III: Lipid-induced nephropathy in type II diabetes
Studies of renal injury III: Lipid-induced nephropathy in type II diabetes
复制标题
DOI：
10.1046/j.1523-1755.2000.00814.x
复制
发表时间：
2000-01-01
影响因子：
19.6
通讯作者：
Peterson, R
中科院分区：
文献类型：
--
作者：
Dominguez, JH;Tang, NJ;Peterson, R
背景在实验和临床情况下，循环脂质升高会导致肾毒性。我们在伴有2型糖尿病和血脂异常的大鼠中检验了脂诱导性肾病导致晚期肾功能衰竭的假设。对自发性高血压性心力衰竭大鼠（SHHF/Gmi-fa）和LA/NIH肥胖大鼠（LA/N-fa）的第一代（F1）杂种大鼠进行了为期41周的研究。第1组（14只大鼠）摄入11.5%蛋白质、47.9%脂肪和40.6%碳水化合物。第2组（8只）摄入26.9%蛋白质、16.7%动物脂肪和56.4%碳水化合物;第3组（20只）摄入20.2%蛋白质、40.4%大豆和椰子油和39.4%碳水化合物。高血压是更严重的大鼠组1和2比组3。相反，循环胆固醇和氢过氧化物水平在第3组中最高，在第2组中居中，在第1组中最低。第3组继发于肾小球硬化和肾小管间质疾病的严重肾衰竭，肾小球和肾微血管中脂质过氧化应激生物标志物4-羟基壬烯醛显著沉积。此外，在第3组中，动脉壁厚度增加也意味着血管损伤。相比之下，糖基氧化应激生物标志物戊糖苷和羧甲基赖氨酸优先定位于第1组和第2组高血糖大鼠的肾小管，并且不与最严重的肾损伤分离。肾小球和间质纤维化伴随着肾转化生长因子β 1水平的成比例增加，其中第3组高胆固醇血症大鼠比第1组高血糖大鼠高3倍。2型糖尿病大鼠非结节性肾小球硬化和肾小管间质疾病的发生依赖于脂氧化应激另一方面，在没有高胆固醇血症的情况下，长期的糖氧化应激似乎不是唯一的肾毒性。
Background. Nephrotoxicity from elevated circulating lipids occurs in experimental and clinical situations. We tested the hypothesis that lipid-induced nephropathy causes advanced renal failure in rats with type II diabetes and dyslipidemia.Methods. First generation (F1) hybrid rats derived from the spontaneous hypertensive heart failure rat (SHHF/Gmi-fa) and the LA/NIH-corpulent rat (LA/N-fa) were studied for 41 weeks while being on specific diets. Group 1 (14 rats) ingested 11.5% protein, 47.9% fat, and 40.6% carbohydrate. Group 2 (8 rats) ingested 26.9% protein, 16.7% animal fat, and 56.4% carbohydrate, and group 3 (20 rats) ingested 20.2% protein, 40.4% soy and coconut oil, and 39.4% carbohydrate.Results. Hyperglycemia was more severe in rat groups 1 and 2 than in group 3. In contrast, circulating cholesterol and hydroperoxide levels were highest in group 3, intermediate in group 2, and lowest in group 1. Group 3 had severe renal failure secondary to glomerulosclerosis and tubulointerstitial disease, with striking deposition of the lipid peroxidation stress biomarker 4-hydroxynonenal in glomeruli and renal microvessels. Moreover, in group 3, increased arterial wall thickness also connoted vascular injury. In contrast, the glycoxidation stress biomarkers pentosidine and carboxymethyl-lysine were preferentially localized to renal tubules of hyperglycemic rats in groups 1 and 2 and did not segregate with the most severe renal injury. Glomerular and interstitial fibrosis was accompanied by proportional increases in renal transforming growth factor-beta 1 levels, which were threefold higher in the hypercholesterolemic rats of group 3 than in the hyperglycemic rats of group 1.Conclusions. Acquisition of non-nodular glomerular sclerosis and tubulointerstitial disease is dependent on lipoxidation stress in rats with type II diabetes. On the other hand, in the absence of hypercholesterolemia, prolonged glycoxidation stress does not appear to be uniquely nephrotoxic.