齐墩果酸和熊果酸对糖尿病小鼠肾脏的抗糖基化作用。
Anti-glycative effects of oleanolic acid and ursolic acid in kidney of diabetic mice.
机构信息
Department of Nutritional Science, Chung Shan Medical University, Taichung City, Taiwan.
出版信息
Eur J Pharmacol. 2010 Feb 25;628(1-3):255-60. doi: 10.1016/j.ejphar.2009.11.019. Epub 2009 Nov 14.
Inhibitory effects of oleanolic acid (OA) and ursolic acid (UA) on aldose reductase (AR) and glycative products in kidney of diabetic mice were examined. OA or UA at 0.05, 0.1 or 0.2% was supplied for 10 weeks. Diabetic mice with 0.1 or 0.2% OA or UA treatments had significantly higher body weight and lower kidney weight at weeks 5 and 10 (P<0.05). OA or UA intake at 0.1 or 0.2% increased their content in the kidney, dose-dependently decreased plasma glucose, HbA1c, renal N(epsilon)-(carboxymethyl)lysine, urinary glycated albumin and urinary albumin levels; elevated plasma insulin and renal creatinine clearance levels; as well as decreased renal sorbitol and fructose concentrations (P<0.05). OA or UA treatments at 0.1 and 0.2% also significantly diminished renal AR activity and dose-dependently down-regulated renal AR mRNA expression (P<0.05). These two compounds at 0.2% significantly reduced renal sorbitol dehydrogenase activity (P<0.05). OA, not UA, treatments at 0.1 or 0.2% dose-dependently enhanced renal glyoxalase I (GLI) activity, up-regulated renal GLI mRNA expression and lowered renal methylglyoxal level (P<0.05). Based on these marked anti-glycative effects, the supplement of OA or UA might be helpful for the prevention or alleviation of glycation associated renal diseases.
考察了齐墩果酸（OA）和熊果酸（UA）对糖尿病小鼠醛糖还原酶（AR）和糖基化产物的抑制作用。0.05%、0.1%或 0.2%的 OA 或 UA 喂养 10 周。用 0.1%或 0.2%OA 或 UA 治疗的糖尿病小鼠在第 5 周和第 10 周时体重显著增加，肾脏重量显著降低（P<0.05）。OA 或 UA 摄入 0.1%或 0.2%可增加其在肾脏中的含量，剂量依赖性地降低血浆葡萄糖、HbA1c、肾 N（epsilon）-（羧甲基）赖氨酸、尿糖化白蛋白和尿白蛋白水平；提高血浆胰岛素和肾肌酐清除率水平；以及降低肾山梨醇和果糖浓度（P<0.05）。OA 或 UA 治疗 0.1%和 0.2%还显著降低了肾 AR 活性，并剂量依赖性地下调了肾 AR mRNA 表达（P<0.05）。这两种化合物在 0.2%时显著降低了肾山梨醇脱氢酶活性（P<0.05）。OA，而不是 UA，在 0.1%或 0.2%剂量依赖性地增强了肾乙二醛酶 I（GLI）活性，上调了肾 GLI mRNA 表达，并降低了肾甲基乙二醛水平（P<0.05）。基于这些明显的抗糖化作用，OA 或 UA 的补充可能有助于预防或缓解糖基化相关的肾脏疾病。
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