Abstract：
Polyuria is an early sign of diabetic nephropathy (DN) that produces dehydration in diabetic patients. This could be caused by alteration of renal aquaporin 2 (AQP2) expression. This study aimed to describe the relation between autophagy modulation via intermittent fasting (IF) and renal AQP2 expression and polyuria in case of DN. We divided the rats into control, DN and IF groups. After 2 and 4 weeks of diabetes induction, blood glucose (BG), serum creatinine (Scr), urine volume, and 24 hours urine protein (UP) were examined. Diabetic nephropathy histopathological index (DNHI) was calculated to evaluate histopathological changes. Immunohistochemistry and real-time PCR were performed to measure the levels of AQP2 and the autophagy marker; LC3 in kidney tissue. DNHI was correlated to the PCR and immunoexpression of AQP2 and LC3. Intermittent fasting significantly decreased the BG, Scr, urine volume, 24 hours UP, and DNHI as compared diabetes. Diabetes significantly elevated the immunoreactivity and mRNA expression levels of AQP2 and LC3 as compared to the control. However, the IF decreased AQP2 and stimulated autophagy in cyclic fashion. Our data revealed significant positive correlations between AQP2 and LC3 at the level of immunoexpression and mRNA at 2nd weeks. Taken together, these data showed that autophagy stimulation didn\'t regulate AQP2 expression in case of diabetic nephropathy, however IF decreased polyuria through improvement of glycemic state.
摘要：
多尿是糖尿病肾病（DN）的早期征兆，可在糖尿病患者中产生脱水。这可能是由肾脏水通道蛋白2（AQP2）表达的改变引起的。本研究旨在描述间歇性禁食（IF）自噬与肾脏AQP2表达与DN多尿症的关系。我们把老鼠分成对照组，DN和IF组。糖尿病诱导2周和4周后，血糖（BG），血清肌酐(Scr),尿量,并检查24小时尿蛋白（UP）。计算糖尿病肾病组织病理学指数（DNHI）以评估组织病理学变化。采用免疫组化和实时荧光定量PCR检测肾组织AQP2和自噬标志物LC3的水平。DNHI与AQP2和LC3的PCR和免疫表达相关。间歇性禁食显著降低BG,Scr,尿量,24小时以上,与DNHI相比，糖尿病。与对照组相比，糖尿病显着提高了AQP2和LC3的免疫反应性和mRNA表达水平。然而,IF以循环方式降低AQP2并刺激自噬。我们的数据显示，在第2周时，AQP2和LC3在免疫表达水平和mRNA水平上呈显着正相关。一起来看,这些数据表明，在糖尿病肾病的情况下，自噬刺激不能调节AQP2的表达，然而，如果通过改善血糖状态减少多尿。
