Section of Cardio-Renal Physiology and Medicine, Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama.
Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama.
Acta Physiol (Oxf). 2019 May;226(1):e13227. doi: 10.1111/apha.13227. Epub 2018 Dec 23.
Chronic high salt intake exaggerates renal injury and inflammation, especially with the loss of functional ET receptors. Tauroursodeoxycholic acid (TUDCA) is a chemical chaperone and bile salt that is approved for the treatment of hepatic diseases. Our aim was to determine whether TUDCA is reno-protective in a model of ET receptor deficiency with chronic high salt-induced renal injury and inflammation.
ET -deficient and transgenic control rats were placed on normal (0.8% NaCl) or high salt (8% NaCl) diet for 3 weeks, receiving TUDCA (400 mg/kg/d; ip) or vehicle. Histological and biochemical markers of kidney injury, renal cell death and renal inflammation were assessed.
In ET -deficient rats, high salt diet significantly increased glomerular and proximal tubular histological injury, proteinuria, albuminuria, excretion of tubular injury markers KIM-1 and NGAL, renal cortical cell death and renal CD4 T cell numbers. TUDCA treatment increased proximal tubule megalin expression as well as prevented high salt diet-induced glomerular and tubular damage in ET -deficient rats, as indicated by reduced kidney injury markers, decreased glomerular permeability and proximal tubule brush border restoration, as well as reduced renal inflammation. However, TUDCA had no significant effect on blood pressure.
TUDCA protects against the development of glomerular and proximal tubular damage, decreases renal cell death and inflammation in the renal cortex in rats with ET receptor dysfunction on a chronic high salt diet. These results highlight the potential use of TUDCA as a preventive tool against chronic high salt induced renal damage.
慢性高盐摄入可加重肾脏损伤和炎症，尤其是在功能性 ET 受体丧失的情况下。牛磺熊脱氧胆酸（TUDCA）是一种化学伴侣和胆盐，已被批准用于治疗肝脏疾病。我们的目的是确定 TUDCA 在 ET 受体缺乏的慢性高盐诱导的肾脏损伤和炎症模型中是否具有肾脏保护作用。
将 ET 缺陷型和转基因对照大鼠分别置于正常盐（0.8%NaCl）或高盐（8%NaCl）饮食 3 周，同时给予 TUDCA（400mg/kg/d；腹腔注射）或载体。评估肾脏损伤、肾细胞死亡和肾脏炎症的组织学和生化标志物。
在 ET 缺陷型大鼠中，高盐饮食显著增加肾小球和近端肾小管的组织损伤、蛋白尿、白蛋白尿、肾小管损伤标志物 KIM-1 和 NGAL 的排泄、肾皮质细胞死亡和肾 CD4 T 细胞数量。TUDCA 治疗增加了近端肾小管的 megalin 表达，并预防了 ET 缺陷型大鼠高盐饮食引起的肾小球和肾小管损伤，表现为肾脏损伤标志物减少、肾小球通透性降低和近端肾小管刷状缘恢复，以及肾脏炎症减少。然而，TUDCA 对血压没有显著影响。
TUDCA 可防止 ET 受体功能障碍大鼠在慢性高盐饮食中肾小球和近端小管损伤的发展，减少肾皮质中的肾细胞死亡和炎症。这些结果强调了 TUDCA 作为预防慢性高盐诱导的肾脏损伤的潜在工具的应用。
