Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Chongqing Medical University, 76 Linjiang Road, Yuzhong District, Chongqing 400010, China.
J Endocrinol Invest. 2013 Jul-Aug;36(7):453-9. doi: 10.3275/8764. Epub 2012 Nov 27.
Thioredoxin-interacting protein (Txnip), an inhibitor of thioredoxin (Trx), increases in diabetic nephropathy and promotes oxidative stress. The angiotensin II (Ang II) receptor blocker telmisartan may protect renal function in diabetic models and patients via multiple effects including antioxidation. However, its mechanism has not been fully elucidated, and its relationship to Txnip remains unclear.
This study aimed to investigate whether telmisartan ameliorates oxidative stress by regulating Txnip and Trx expression in Type 2 diabetic rat kidneys and explore the possible relationship between renoprotection by telmisartan and Txnip.
Twenty-one rats were equally divided into control (C), streptozotocin-induced diabetic (D), and telmisartan- treated diabetic (T) groups. Txnip and Trx expression in rat kidneys was analyzed by immunohistochemistry, RTPCR, and western blot. Peroxisome proliferator-activated receptor- γ (PPARγ), NADPH oxidase activity, and parameters of renal function and oxidative stress were also measured.
Trx and PPARγ were significantly decreased, and Txnip expression and NADPH oxidase activity markedly increased, in the D and T groups compared to the C group. After telmisartan treatment, Trx and PPARγ were upregulated, while Txnip expression and NADPH oxidase activity were downregulated. Parameters of renal function and oxidative stress were improved by telmisartan.
Telmisartan ameliorates oxidative stress and protects renal function in Type 2 diabetic rat kidneys. The downregulation of Txnip by telmisartan may be associated with PPARγ activation.
硫氧还蛋白相互作用蛋白（Txnip）是硫氧还蛋白（Trx）的抑制剂，在糖尿病肾病中增加，并促进氧化应激。血管紧张素 II（Ang II）受体阻滞剂替米沙坦可能通过多种作用，包括抗氧化作用，来保护糖尿病模型和患者的肾功能。然而，其机制尚未完全阐明，其与 Txnip 的关系尚不清楚。
本研究旨在探讨替米沙坦是否通过调节 2 型糖尿病大鼠肾脏中的 Txnip 和 Trx 表达来改善氧化应激，并探讨替米沙坦的肾保护作用与 Txnip 之间的可能关系。
21 只大鼠平均分为对照组（C）、链脲佐菌素诱导的糖尿病组（D）和替米沙坦治疗的糖尿病组（T）。通过免疫组织化学、RTPCR 和 Western blot 分析大鼠肾脏中 Txnip 和 Trx 的表达。还测量了过氧化物酶体增殖物激活受体-γ（PPARγ）、NADPH 氧化酶活性以及肾功能和氧化应激的参数。
与 C 组相比，D 组和 T 组的 Trx 和 PPARγ 显著降低，而 Txnip 表达和 NADPH 氧化酶活性显著增加。替米沙坦治疗后，Trx 和 PPARγ 上调，而 Txnip 表达和 NADPH 氧化酶活性下调。替米沙坦改善了肾功能和氧化应激的参数。
替米沙坦改善了 2 型糖尿病大鼠肾脏的氧化应激和肾功能。替米沙坦下调 Txnip 可能与 PPARγ 激活有关。
