Department of Endocrinology and Metabolism, Kunshan Hospital Afffiliated to Jiangsu University, Kunshan, Nanjing, 215300, China.
Department of Endocrinology and Metabolism, Jiangsu Hospital of Traditional Chinese Medicine, Nanjing, 210029, China.
Curr Med Sci. 2020 Dec;40(6):1114-1120. doi: 10.1007/s11596-020-2304-z. Epub 2021 Jan 11.
Angiopoietin-like protein 2 (ANGPTL2) stimulates inflammation and is important in the pathogenesis of diabetic kidney disease (DKD). Irbesartan is helpful in reducing diabetes-induced renal damage. In this study, the effects of irbesartan on DKD and its renal protective role involving ANGPTL2 in DKD rats were examined. Wistar rats were divided into normal, DKD, and DKD + irbesartan groups. The DKD + irbesartan group was treated once daily for 8 weeks with 50 mg/kg irbesartan via intragastric gavage. The 24-h urinary albumin was determined each week, renal pathological changes were observed, and expression of ANGPTL2 and nuclear factor-kappa B (NF-κB) in rat renal tissue was assessed by immunohistochemistry. Mouse podocytes cultured in a high concentration of glucose were classified into four groups based on the irbesartan concentrations (0, 25, 50, and 75 ºg/mL). Expression of ANGPTL2 and phosphorylated IκB-α was assessed by Western blotting. The mRNA levels of ANGPTL2 and monocyte chemotactic protein 1 (MCP-1) were assessed by real-time polymerase chain reaction. The DKD rats displayed proteinuria, podocyte injury, and increased ANGPTL2 and NF-κB expression. All were relieved by irbesartan treatment. In podocytes cultured in elevated glucose, ANGPTL2 and phosphorylated IκB-α were overexpressed at the protein level, and ANGPTL2 and MCP-1 were highly expressed at the mRNA level. Irbesartan down-regulated ANGPTL2 and phosphorylated IκB-αexpression at the protein level and inhibited ANGPTL2 and MCP-1 expression at the mRNA level. The ameliorative effects of irbesartan against DKD involves podocyte protection and suppression of ANGPTL2.
血管生成素样蛋白 2（ANGPTL2）可刺激炎症反应，在糖尿病肾病（DKD）的发病机制中起重要作用。厄贝沙坦有助于减少糖尿病引起的肾损伤。在这项研究中，观察了厄贝沙坦对 DKD 的影响及其在 DKD 大鼠中的肾脏保护作用，该作用涉及 DKD 大鼠中的 ANGPTL2。Wistar 大鼠分为正常组、DKD 组和 DKD+厄贝沙坦组。DKD+厄贝沙坦组通过灌胃给予 50mg/kg 厄贝沙坦，每日 1 次，共 8 周。每周测定 24 小时尿白蛋白，观察肾脏病理变化，免疫组化法检测大鼠肾组织中 ANGPTL2 和核因子-κB（NF-κB）的表达。将培养在高浓度葡萄糖中的小鼠足细胞分为厄贝沙坦浓度（0、25、50 和 75 ºg/mL）的 4 组。通过 Western blot 检测 ANGPTL2 和磷酸化 IκB-α的表达。通过实时聚合酶链反应检测 ANGPTL2 和单核细胞趋化蛋白 1（MCP-1）的 mRNA 水平。DKD 大鼠表现出蛋白尿、足细胞损伤和 ANGPTL2 和 NF-κB 表达增加。厄贝沙坦治疗可缓解所有这些情况。在高葡萄糖培养的足细胞中，ANGPTL2 和磷酸化 IκB-α的蛋白水平表达增加，ANGPTL2 和 MCP-1 的 mRNA 水平表达增加。厄贝沙坦可下调 ANGPTL2 和磷酸化 IκB-α的蛋白水平表达，并抑制 ANGPTL2 和 MCP-1 的 mRNA 水平表达。厄贝沙坦对 DKD 的改善作用涉及足细胞保护和抑制 ANGPTL2。
