Riedl Eva, Pfister Frederick, Braunagel Margarita, Brinkkötter Paul, Sternik Paula, Deinzer Martina, Bakker Stephan J L, Henning Rob H, van den Born Jacob, Krämer Bernhard K, Navis Gerjan, Hammes Hans-Peter, Yard Benito, Koeppel Hannes
5th Medical Clinic, University Medicine Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Cell Physiol Biochem. 2011;28(2):279-88. doi: 10.1159/000331740. Epub 2011 Aug 16.
BACKGROUND/AIMS: We identified carnosinase-1 (CN-1) as risk-factor for diabetic nephropathy (DN). Carnosine, the substrate for CN-1, supposedly is a protective factor regarding diabetic complications. In this study, we hypothesized that carnosine administration to diabetic rats might protect the kidneys from glomerular apoptosis and podocyte loss.
We examined the effect of oral L-carnosine administration (1g/kg BW per day) on apoptosis, podocyte loss, oxidative stress, AGEs and hexosamine pathway in kidneys of streptozotocin-induced diabetic Wistar rats after 3 months of diabetes and treatment.
Hyperglycemia significantly reduced endogenous kidney carnosine levels. In parallel, podocyte numbers significantly decreased (-21% compared to non-diabetics, p<0.05), apoptotic glomerular cells numbers increased (32%, compared to non-diabetic, p<0.05) and protein levels of bax and cytochrome c increased (175% and 117%). Carnosine treatment restored carnosine kidney levels, prevented podocytes loss (+23% compared to diabetic, p<0.05), restrained glomerular apoptosis (-34% compared to diabetic; p<0.05) and reduced expression of bax and cytochrome c (-63% and -54% compared to diabetics, both p<0.05). In kidneys of all diabetic animals, levels of ROS, AGEs and GlcNAc-modified proteins were increased.
By inhibition of pro-apoptotic signaling and independent of biochemical abnormalities, carnosine protects diabetic rat kidneys from apoptosis and podocyte loss.
背景/目的：我们确定肌肽酶-1（CN-1）是糖尿病肾病（DN）的一个风险因素。肌肽作为CN-1的底物，据推测是一种针对糖尿病并发症的保护因子。在本研究中，我们假设给糖尿病大鼠施用肌肽可能保护肾脏免受肾小球凋亡和足细胞丢失的影响。
我们检测了口服L-肌肽（每天1g/kg体重）对链脲佐菌素诱导的糖尿病Wistar大鼠肾脏凋亡、足细胞丢失、氧化应激、晚期糖基化终产物（AGEs）和己糖胺途径的影响，糖尿病及治疗持续3个月。
高血糖显著降低内源性肾脏肌肽水平。与此同时，足细胞数量显著减少（与非糖尿病大鼠相比减少21%，p<0.05），凋亡的肾小球细胞数量增加（与非糖尿病大鼠相比增加32%，p<0.05），bax和细胞色素c的蛋白水平升高（分别升高175%和117%）。肌肽治疗恢复了肾脏肌肽水平，防止了足细胞丢失（与糖尿病大鼠相比增加23%，p<0.05），抑制了肾小球凋亡（与糖尿病大鼠相比减少34%；p<0.05），并降低了bax和细胞色素c的表达（与糖尿病大鼠相比分别降低63%和54%，两者均p<0.05）。在所有糖尿病动物的肾脏中，活性氧（ROS）、AGEs和N-乙酰葡糖胺修饰蛋白的水平均升高。
通过抑制促凋亡信号传导且独立于生化异常情况，肌肽可保护糖尿病大鼠肾脏免受凋亡和足细胞丢失的影响。
