Teoh Soon Hui, Miyajima Katsuhiro, Shinozaki Yuichi, Shinohara Masami, Ohata Keiichi, Briand François, Morimoto Rika, Nakamura Yuka, Uno Kinuko, Kemuriyama Noriko, Nakae Dai, Ohta Takeshi, Maekawa Tatsuya
Department of Food and Nutritional Science, Graduate School of Agriculture, Tokyo University of Agriculture.
Department of Nutritional Science and Food Safety, Faculty of Applied Biosciences, Tokyo University of Agriculture.
J Toxicol Sci. 2021;46(12):589-599. doi: 10.2131/jts.46.589.
Type 2 diabetes mellitus represents an international health concern with its growing number of patients worldwide. At the same time, excessive salt consumption is also seen as a major cause of diseases such as hypertension and may expedite renal complications in diabetic patients. In this study, we investigated the effects of excessive sodium chloride supplementation on the kidney of the Spontaneously Diabetic Torii-Lepr (SDT fatty) rat, an obese type 2 diabetes model. Male and female SDT fatty rats and normal Sprague-Dawley (SD) rats at 5 weeks of age were loaded with 0.3% sodium chloride (NaCl) in drinking water for 13 weeks. Blood serum and urinary parameters were observed throughout the experiment and kidney samples were examined in histopathological and genetical analyses. Significant changes on the body weight, blood pressure, urine volume, creatinine clearance, blood urea nitrogen (BUN), relative gene expressions of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), monocyte chemotactic protein-1 (MCP-1) and transforming growth factor-β (TGF-β) were observed in the salt-loaded male SDT fatty rats. Urinary L-type fatty acid-binding protein (L-FABP) and albumin levels were higher observed in the salt-loaded male SDT fatty rats throughout the period, but urinary albumin levels in the female SDT fatty rats remain unchanged. In the kidney, slight Armani-Ebstein changes, tubular degeneration, hyaline cast, and inflammatory cell infiltration were observed in female SDT fatty rats while the levels of some changes were higher in the salt-loaded group. The kidney of the salt-loaded male SDT fatty rats demonstrated a higher degree of lesions compared to the female group and the male unloaded group. Histopathological changes in salt-loaded SDT fatty rats show that excessive salt consumption may act as a diabetic pathology exacerbation factor, but the pathology may be influenced by gender difference. Urinary L-FABP levels may act as a useful biomarker to detect slight tubular damages in the kidney. Excessive salt loading was shown to exacerbate the renal injury in SDT fatty rats.
2型糖尿病是一个国际健康问题，全球患者数量不断增加。与此同时，过量摄入盐分也被视为高血压等疾病的主要病因，并且可能加速糖尿病患者的肾脏并发症。在本研究中，我们调查了过量补充氯化钠对肥胖型2型糖尿病模型——自发性糖尿病Torii-Lepr（SDT肥胖）大鼠肾脏的影响。5周龄的雄性和雌性SDT肥胖大鼠以及正常的Sprague-Dawley（SD）大鼠饮用含0.3%氯化钠（NaCl）的水13周。在整个实验过程中观察血清和尿液参数，并对肾脏样本进行组织病理学和遗传学分析。在摄入盐分的雄性SDT肥胖大鼠中，观察到体重、血压、尿量、肌酐清除率、血尿素氮（BUN）、肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）、单核细胞趋化蛋白-1（MCP-1）和转化生长因子-β（TGF-β）的相对基因表达有显著变化。在整个期间，摄入盐分的雄性SDT肥胖大鼠尿液中的L型脂肪酸结合蛋白（L-FABP）和白蛋白水平较高，但雌性SDT肥胖大鼠的尿液白蛋白水平保持不变。在雌性SDT肥胖大鼠的肾脏中，观察到轻微的阿马尼-埃布斯坦变化、肾小管变性、透明管型和炎症细胞浸润，而在摄入盐分的组中某些变化的程度更高。与雌性组和未摄入盐分的雄性组相比，摄入盐分的雄性SDT肥胖大鼠的肾脏病变程度更高。摄入盐分的SDT肥胖大鼠的组织病理学变化表明，过量摄入盐分可能作为糖尿病病理加重因素，但这种病理可能受性别差异影响。尿液L-FABP水平可能作为检测肾脏轻微肾小管损伤的有用生物标志物。结果表明，过量摄入盐分加剧了SDT肥胖大鼠的肾脏损伤。
