Guo Qiongqiong, Wang Junxia
Department of Blood Purification Center, the First Affiliated Hospital of Henan University of Science and Technology, Luoyang, China.
J Biochem Mol Toxicol. 2025 Jul;39(7):e70377. doi: 10.1002/jbt.70377.
Hypertension-induced renal injury arises from endothelial dysfunction and elevated glomerular permeability. Telmisartan, an Angiotensin II (Ang II) receptor blocker (ARB), is commonly used to treat hypertension and is known for its long-lasting effects, as well as its antioxidant and anti-inflammatory properties. However, the effects of Telmisartan on glomerular permeability are less well-documented. This study investigates the protective effects of Telmisartan (TEL), an Ang II receptor blocker, on hypertension-induced kidney damage. Using a mouse model of Angiotensin II/high salt (ANG/HS)-induced hypertension, TEL treatment significantly reduced mean arterial pressure, alleviated renal fibrosis, and improved kidney function, as indicated by lower urinary albumin and serum creatinine levels. TEL also suppressed oxidative stress and reduced the expression of inflammatory markers interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in renal tissues. Furthermore, TEL restored the expression of the tight junction protein zonula occludens-1 (ZO-1) in the glomeruli, which was downregulated in ANG/HS-treated mice. In vitro studies on human renal glomerular endothelial cells (HrGECs) confirmed that TEL reduced endothelial monolayer permeability and restored ZO-1 expression, effects that were mediated by Krüppel-like factor 4 (KLF4). These findings suggest that TEL mitigates glomerular endothelial permeability and kidney damage through antioxidant, anti-inflammatory, and KLF4-dependent mechanisms, offering potential therapeutic benefits for hypertension-related renal damage.
高血压所致肾损伤源于内皮功能障碍和肾小球通透性升高。替米沙坦是一种血管紧张素II（Ang II）受体阻滞剂（ARB），常用于治疗高血压，以其长效作用以及抗氧化和抗炎特性而闻名。然而，替米沙坦对肾小球通透性的影响鲜有文献记载。本研究调查了血管紧张素II受体阻滞剂替米沙坦（TEL）对高血压所致肾损伤的保护作用。使用血管紧张素II/高盐（ANG/HS）诱导的高血压小鼠模型，TEL治疗显著降低平均动脉压，减轻肾纤维化，并改善肾功能，表现为尿白蛋白和血清肌酐水平降低。TEL还抑制氧化应激，并降低肾组织中炎症标志物白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）的表达。此外，TEL恢复了肾小球中紧密连接蛋白闭合蛋白-1（ZO-1）的表达，而在ANG/HS处理的小鼠中该蛋白表达下调。对人肾小球内皮细胞（HrGECs）的体外研究证实，TEL降低内皮单层通透性并恢复ZO-1表达，这些作用由Krüppel样因子4（KLF4）介导。这些发现表明，TEL通过抗氧化、抗炎和KLF4依赖性机制减轻肾小球内皮通透性和肾损伤，为高血压相关肾损伤提供了潜在的治疗益处。
