Astaxanthin attenuates contrast-induced acute kidney injury in rats by inhibiting dynamin-related protein 1-mediated mitochondrial fission through activating SIRT1 pathway
10.3760/cma.j.cn441217-20211227-00101
- VernacularTitle:虾青素通过激活SIRT1通路抑制动力相关蛋白1介导的线粒体分裂减轻大鼠对比剂急性肾损伤
- Author:
Cheng ZHANG
1
;
Di ZHENG
;
Chihao ZHANG
;
Liang SONG
;
Yongli XUAN
;
Wenhua LI
Author Information
1. 徐州医科大学附属医院心内科，徐州 221000
- Keywords:
Acute kidney injury;
Mitochondria;
Rats;
Astaxanthin;
Contrast-induced acute kidney injury;
Mitochondrial fission;
Silent mating type information regulation
- From:
Chinese Journal of Nephrology
2022;38(8):710-717
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate whether astaxanthin (AST) down-regulates dynamin-related protein 1 (Drp1) through activating the silent mating type information regulation 2 homolog-1 (SIRT1) signaling pathway, thereby attenuating contrast-induced acute kidney injury.Methods:Forty adult male Sprague-Dawley rats weighing 160-180 g were randomly divided into five groups: sham surgery group (Sham group), contrast medium injury group (CM group), astaxanthin-intervention group (AST+CM group), SIRT1 inhibitor Ex527 intervention group (Ex527+CM group), and astaxanthin combined with Ex527 intervention group (AST+Ex527+CM group). After 72 hours of modeling, heart blood was removed and kidney tissues were collected for follow-up testing. Serum creatinine (Scr), blood urea nitrogen (BUN), and oxidative stress-related indexes total superoxide dismutase (T-SOD) and malondialdehyde (MDA) were measured by biochemistry; hematoxylin and eosin staining was performed to observe the pathological changes in the kidney; mitochondrial morphology and number were observed by transmission electron microscopy; reactive oxygen species (ROS) levels were detected by ROS staining in frozen sections; TUNEL staining was performed to detect apoptosis level. The expression levels of SIRT1, p53, peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), Drp1 and apoptosis-related proteins Bcl-2 and Bax were detected by Western blotting.Results:(1) Compared with the CM group, Scr and BUN level were significantly lower, T-SOD level was higher and MDA level was lower in the AST+CM group, while T-SOD level decreased and MDA level increased after the combination of Ex527 (all P<0.05). (2) ROS expression was lower in the AST+CM group compared to the CM group and higher after the combination of Ex527 (both P<0.05). (3) The number of apoptotic cells was significantly reduced in the AST+CM group compared to the CM group and increased after the combination of Ex527 (both P<0.05). (4) The protein expression levels of SIRT1, PGC-1α and Bcl-2 were increased and the protein expression levels of p53, Drp1 and Bax were decreased (all P<0.05) in the AST+CM group compared with the CM group, and the protein expression levels of SIRT1, PGC-1α and Bcl-2 were decreased and the protein expression levels of p53, Drp1 and Bax were increased when Ex527 was combined (all P<0.05). Conclusion:Astaxanthin can inhibit Drp1-mediated mitochondrial fission by activating the SIRT1 pathway, thereby reducing contrast-induced acute kidney injury in rats.
