Department of Physiology and Pharmacology, Federal University of Pernambuco, Recife, Brazil.
Department of Physiology and Pharmacology, Federal University of Pernambuco, Recife, Brazil; Department of Histology and Embriology, Federal University of Pernambuco, Recife, Brazil.
Mol Cell Endocrinol. 2024 Dec 1;594:112349. doi: 10.1016/j.mce.2024.112349. Epub 2024 Sep 2.
The vitamin D receptor (VDR) is associated with antioxidative and anti-inflammatory effects and modulation of the renin-angiotensin-aldosterone system. This study evaluated whether VDR agonist paricalcitol protects renal ischemia-reperfusion (IR) induced tubular injury in rats by evaluating: 1) ATP-dependent tubular Na transport; 2) renal redox signaling; 3) renal content of proinflammatory cytokines TNF-α and IL-6; and 4) renal content of renin and angiotensin II receptor type 1 (ATR). Paricalcitol prevented IR-induced tubular injury, evidenced by the prevention of histopathological changes and renal fibrosis with preservation of the activity of ATP-dependent Na transporters in the renal cortex. Paricalcitol decreased renal oxidative stress by reducing NADPH oxidase activity and increasing catalase. Paricalcitol also decreased the renal content of TNF-α, IL-6, and ATR. The NADPH oxidase inhibitor apocynin did not present additive protection to paricalcitol-induced effects. The protective effects of paricalcitol on tubular injury induced by renal IR may dependent on the modulation of redox and proinflammatory signaling and renal angiotensin II/ATR signaling.
维生素 D 受体（VDR）与抗氧化和抗炎作用以及肾素-血管紧张素-醛固酮系统的调节有关。本研究通过评估以下方面来评估 VDR 激动剂帕立骨化醇是否通过以下方式保护大鼠肾缺血再灌注（IR）诱导的肾小管损伤：1）ATP 依赖性管状 Na 转运；2）肾氧化还原信号；3）促炎细胞因子 TNF-α和 IL-6 的肾含量；和 4）肾素和血管紧张素 II 受体 1（ATR）的含量。帕立骨化醇通过防止组织病理学变化和肾纤维化，同时保持肾皮质中 ATP 依赖性 Na 转运体的活性，从而预防 IR 诱导的肾小管损伤。帕立骨化醇通过降低 NADPH 氧化酶活性和增加过氧化氢酶来减少肾氧化应激。帕立骨化醇还降低了 TNF-α、IL-6 和 ATR 的肾含量。NADPH 氧化酶抑制剂 apocynin 对帕立骨化醇诱导的作用没有附加保护作用。帕立骨化醇对肾 IR 诱导的肾小管损伤的保护作用可能依赖于氧化还原和促炎信号以及肾血管紧张素 II/ATR 信号的调节。
