期刊
FOOD AND CHEMICAL TOXICOLOGY
卷 135, 期 -, 页码 -出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.fct.2019.110901
关键词
Acute kidney injury; Salvianolic acid A; Oxidative stress; Inflammatory; Lipopolysaccharide
资金
- National Natural Science Foundation of China [81803766]
- Natural Science Foundation of Shandong Province [ZR2018BH036]
- China's Post-doctoral Science Fund [2019M652336]
- Qingdao Postdoctoral Application Research Project
- Shandong Key Research and Development Program [2018GSF118124]
Acute kidney injury (AKI) is an abrupt loss of kidney function with high mortality. Inflammatory is considered driving the progression of AKI. Salvianolic acid A (SA), one of the major ingredients of Salvia miltiorrhiza Bunge, displays plenty of biological effects. Herein, the effect of SA on lipopolysaccharide (LPS)-induced AKI in mice and further related mechanism in inflammatory cells were explored. In vivo experiments demonstrated that SA significantly ameliorated LPS-challenged MU by preventing glomerulus atrophy and decreasing plasma creatinine and blood urea nitrogen (BUN) levels. Meanwhile, SA significantly decreased the release of serum inflammatory cytokines and blocked macrophage infiltration in damaged renal tissue. In in vitro studies, SA significantly decreased TNF-alpha and IL-6 release levels and altered the expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in LPS-stimulated macrophages, which were consistent with the results from in vivo experiments. Furthermore, SA that bound to Toll-Like Receptor 4 (TLR4) was able to reduce endoplasmic reticulum (ER) stress and reactive oxygen species (ROS) generation in response to LPS stimulation. All silence of TLR4 gene, ROS scavenger and Ca2+ chelator decreased inflammatory cytokines releases. Taken together, SA could be used as a potential therapeutic agent for preventing AKI by suppressing inflammatory responses.
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