College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China.
Heilongjiang Province Key Laboratory of Pathogenic Mechanism for Animal Disease and Comparative Medicine, Harbin 150030, China.
Int J Mol Sci. 2023 Jan 4;24(2):969. doi: 10.3390/ijms24020969.
Effective and targeted prevention and treatment methods for acute kidney injury (AKI), a common clinical complication, still needs to be explored. Paricalcitol is a biologically active chemical that binds to vitamin D receptors in the body to exert anti-oxidant and anti-inflammatory effects. However, the molecular mechanism of the effect of paricalcitol on AKI remains unclear. The current study uses a paricalcitol pretreatment with a mouse AKI model induced by cisplatin to detect changes in renal function, pathology and ultrastructure. Results showed that paricalcitol significantly improved renal function in mice and reduced inflammatory cell infiltration and mitochondrial damage in renal tissue. Furthermore, paricalcitol markedly suppressed reactive oxygen species and malondialdehyde levels in the kidneys of AKI mice and increased the levels of glutathione, superoxide dismutase, Catalase and total anti-oxidant capacity. In addition, we detected renal necrosis and inflammation-related proteins in AKI mice by immunofluorescence and Western blot, and found that their levels were markedly decreased after paricalcitol pretreatment. Moreover, paricalcitol promotes nuclear factor erythroid 2-related factor 2 () in the nucleus and activates the /heme oxygenase-1 () signaling pathway; while HO-1 is inhibited, the protective effect of paricalcitol on the kidney is attenuated. In conclusion, paricalcitol exerts a renoprotective effect by decreasing renal oxidative injury and inflammation through / signaling, providing a new insight into AKI prevention.
有效且有针对性的急性肾损伤 (AKI) 防治方法仍需探索，AKI 是一种常见的临床并发症。帕立骨化醇是一种具有生物活性的化学物质，它与体内的维生素 D 受体结合，发挥抗氧化和抗炎作用。然而，帕立骨化醇对 AKI 影响的分子机制尚不清楚。本研究采用帕立骨化醇预处理顺铂诱导的 AKI 小鼠模型，检测肾功能、病理和超微结构的变化。结果表明，帕立骨化醇可显著改善 AKI 小鼠的肾功能，减少肾组织中炎性细胞浸润和线粒体损伤。此外，帕立骨化醇可显著抑制 AKI 小鼠肾脏中活性氧和丙二醛水平，并增加谷胱甘肽、超氧化物歧化酶、过氧化氢酶和总抗氧化能力水平。此外，我们通过免疫荧光和 Western blot 检测 AKI 小鼠的肾坏死和炎症相关蛋白，发现帕立骨化醇预处理后其水平明显降低。此外，帕立骨化醇促进核因子红细胞 2 相关因子 2 () 在核内的表达，并激活 /血红素加氧酶-1 () 信号通路；而抑制 HO-1 后，帕立骨化醇对肾脏的保护作用减弱。总之，帕立骨化醇通过减少肾脏氧化损伤和炎症发挥肾脏保护作用，通过 / 信号通路为 AKI 的防治提供了新的思路。
