Rosiglitazone Suppresses Renal Crystal Deposition by Ameliorating Tubular Injury Resulted from Oxidative Stress and Inflammatory Response via Promoting the Nrf2/HO‐1 Pathway and Shifting Macrophage Polarization

作者：Hongyan Lu, Xifeng Sun, Min Jia, Fa Sun, Jianguo Zhu, Xiaolong Chen, Kun Chen, Kehua Jiang · 发表于：Oxidative Medicine and Cellular Longevity · 年份：2021 · DOI：10.1155/2021/5527137 · 被引用次数：37 · 研究领域：Kidney Stones and Urolithiasis Treatments、Renal function and acid-base balance、Acute Kidney Injury Research

Oxidative stress and inflammatory response are closely related to nephrolithiasis. This study is aimed at exploring whether rosiglitazone (ROSI), a regulator of macrophage (Mp) polarization, could reduce renal calcium oxalate (CaOx) deposition by ameliorating oxidative stress and inflammatory response. Male C57 mice were equally and randomly divided into 7 groups. Kidney sections were collected on day 5 or day 8 after treatment. Pizzolato staining and polarized light optical microscopy were used to detect crystal deposition. PAS staining and TUNEL assay were performed to assess the tubular injury and cell apoptosis, respectively. Gene expression was assessed by immunohistochemistry, immunofluorescence, ELISA, qRT‐PCR, and Western blot. The reactive oxygen species (ROS) level was assessed using a fluorescence microplate and fluorescence microscope. Hydrogen peroxide (H 2 O 2 ), malonaldehyde (MDA), and glutathione (GSH) were evaluated to determine oxidative stress. Lactic dehydrogenase (LDH) activity was examined to detect cell injury. Adhesion of CaOx monohydrate (COM) crystals to HK‐2 cells was detected by crystal adhesion assay. HK‐2 cell death or renal macrophage polarization was assessed by flow cytometry. In vivo , renal crystal deposition, tubular injury, crystal adhesion, cell apoptosis, oxidative stress, and inflammatory response were significantly increased in the 7‐day glyoxylic acid‐ (Gly‐) treated group but were decreased in the ROSI‐treated groups, especially in ...