早期应用低蛋白加α酮酸饮食对延缓KK-Ay小鼠糖尿病肾病进展的作用

Slowing Progression of Diabetic Nephropathy in KK-Ay Mice by Early Using Low Protein Diet Associate with α-ketose

目的:观察早期应用低蛋白加α酮酸饮食对2型糖尿病肾病动物模型KK-Ay小鼠肾脏病变的影响,并探讨其作用机制。方法:雄性KK-Ay小鼠30只,12周龄开始给予不同饮食干预,分为正常蛋白组(22%酪蛋白,NPD组)15只和低蛋白加α酮酸组(5%酪蛋白+1%α酮酸,Keto组)15只;另设性别周龄相同的C57/BL6J小鼠15只为对照(CON组),始终给予正常蛋白饮食。检测第8、14、20周龄各组小鼠尿白蛋白,血清中葡萄糖、胰岛素、糖化血红蛋白、胆固醇、三酰甘油、尿素氮、肌酐、白蛋白等生化变化。对20周龄小鼠肾组织病理进行图文分析和半定量检测,免疫组化方法测定肾组织中TGF-β、FN表达量。结果:Keto组小鼠14周龄时血糖、ACR(白蛋白/肌酐)、尿白蛋白排泄率、三酰甘油低于NPD组(P<0.05),20周龄时糖化血红蛋白、血胰岛素、肾小球面积及系膜区面积显著降低(P<0.05)。免疫组化结果显示NPD组小鼠肾内TGF-β蛋白表达及肾小球FN沉积明显增多(P<0.05)。结论:早期应用低蛋白加α酮酸饮食能够显著降低KK-Ay小鼠尿白蛋白,减轻系膜基质增生和结节性硬化,而不引起营养不良,并可能通过减少TGF-β表达抑制FN等系膜基质增加而延缓糖尿病肾病的进展。

Objective：To evaluate the effects of early low protein diet （LPD）supplemented with α- keto acid on diabetic nephropathy of type 2 diabetes mellitus in KK -Ay mice,and to elucidate the mechanisms involved. Methods：30 male 12 - weekage KK - Ay mice were divided into two groups,normal protein diet group（22 % casein diet, n = 15） and LPD＋α - keto group （5% casein ＋ 1%a - keto, n = 15）. 15 sex - and - age matched C57/BL6J mice were served as the control group. Urine album,serum glucose, insulin, lipids, albumin, creatinine and urea nitrogen were measured at the age of 8,14 and 20 weeks. Renal tissue was observed to assess pathologic change. Immunohistochemistry method was used to evaluate the extent of expression of TGF - β and FN. Re- suits：The levels of urine album, serum glucose, triglyceride in LPD ＋ α- keto group were significantly lower than that in NPD group after 14 weeks （P〈 0.05）. There were significant differences in glycosylated hemoglobin, insulin and area of mesangial region after treated than before at groups NPD and keto （P〈0.05）. Expressions of TGF- β and FN were also lower in keto group （P〈0.05）. Conclusion： LPD supplemented with α - keto acid can protect early diabetic kidney from malnutrition and aggravation of metabolic disturbance. Keto acid may ameliorate the renal fibrosis by reducing the expressions of TGF- β and FN.