Baicalin Alleviates Contrast-Induced Acute Kidney Injury Through ROS/NLRP3/Caspase-1/GSDMD Pathway-Mediated Proptosis in vitro

作者全名："Li, Yanyan; Wang, Junda; Huang, Dan; Yu, Chao"

作者地址："[Li, Yanyan; Yu, Chao] Chongqing Med Univ, Coll Pharm, Chongqing, Peoples R China; [Li, Yanyan; Wang, Junda; Huang, Dan] Chongqing Tradit Chinese Med Hosp, Chongqing, Peoples R China; [Yu, Chao] Chongqing Med Univ, Coll Pharm, Yixueyuan Rd, Chongqing 400016, Peoples R China"

通信作者："Yu, C (通讯作者)，Chongqing Med Univ, Coll Pharm, Yixueyuan Rd, Chongqing 400016, Peoples R China."

来源：DRUG DESIGN DEVELOPMENT AND THERAPY

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:000863440700001

JCR分区：Q1

影响因子：4.8

年份：2022

卷号：16

期号：　

开始页：3353

结束页：3364

文献类型：Article

关键词：pyroptosis; baicalin; iohexol; ROS; NLRP3; Caspase-1; GSDMD pathway; kidney injury

摘要："Purpose: To investigate the effect of baicalin on the reactive oxygen species (ROS)/ NOD-like receptor protein 3 (NLRP3)/Caspase-1/gasdermin-D (GSDMD) inflammasome pathway and its related mechanism in regulating pyroptosis of human renal tubular epithelial cells (HK-2) induced by contrast media.Methods: Iohexol was used to act on HK-2 cells to establish a renal tubular cell pyroptosis model; and the signal pathway genes were silenced, cytokines were detected by enzyme-linked immunosorbent assay (ELISA), and cell viability, gene expression, and protein expression were evaluated by double fluorescence staining and flow cytometry. To assess the cytotoxicity caused by the contrast agent; cells were pretreated with different concentrations of baicalin; and then the cells were exposed to iohexol again, and the relevant indicators were tested again.Results: After HK-2 cells were exposed to iohexol, the NLRP3 inflammasome pathway markers NLRP3, interleukin (IL)-113, and IL-18 mRNA levels as well as the protein expression levels of NLRP3, ASC, Caspase-1, and GSDMD were up-regulated. In addition, the effect also significantly increased the IL-18, IL-113, lactate dehydrogenase (LDH), superoxide dismutase (SOD), malondialdehyde (MDA) release, and cellular ROS levels. The results of Annexin V-FITC/PI flow cytometry showed that the level of apoptosis was increased. However, after the intervention of baicalin, the changes in the above indexes caused by iohexol stimulation of HK-2 cells were inhibited.Conclusion: Exposure to iohexol can induce pyroptosis of HK-2 cells through the ROS/NLRP3/Caspase-1/GSDMD signaling pathway. Baicalin ameliorated iohexol-induced pyroptosis in HK-2 cells by regulating the NLRP3 inflammasome pathway."

基金机构："Natural Science Foundation of Chongqing, China [cstc2020jcyj-msxmX0187]; Chongqing Science and health joint traditional Chinese medicine science and technology project, China [2020ZY3539]"

基金资助正文："Natural Science Foundation of Chongqing in 2020 (cstc2020jcyj-msxmX0187), China; Chongqing Science and health joint traditional Chinese medicine science and technology project in 2020 (2020ZY3539), China."