Gao Dongmei, Wang Hu, Xu Yang, Zheng Di, Zhang Quan, Li Wenhua
Institute of Cardiovascular Disease Research, Xuzhou Medical University, Xuzhou, 221002, Jiangsu, China.
Department of Cardiology, The Affiliated Hospital of Xuzhou Medical University, No.99 Huaihai West Road, Xuzhou, 221002, Jiangsu, China.
Int Urol Nephrol. 2019 Feb;51(2):351-358. doi: 10.1007/s11255-018-2027-2. Epub 2018 Nov 19.
The present study was designed to further investigate the protective effect of astaxanthin (AST) on contrast-induced acute kidney injury (CI-AKI) in rats and the relationship between SIRT1-p53 pathway and astaxanthin.
40 adult male Sprague Dawley (SD) rats were randomly divided into five groups (n = 8/group): control (CON), normal rats treated with AST (AST), CM-treated (CM), CM rats treated with isoform of nitric oxide synthase (iNOS) inhibitor (iNOS + CM), and CM rats treated with AST (AST + CM). Serum creatinine (Scr) and blood urea nitrogen (BUN) values were measured at 72 h following the procedure. Hematoxylin and eosin (H-E) staining was used to observe the pathologic changes of kidney. Tunel staining was used to test apoptosis of kidney tubules. Oxidative stress, SIRT1 activity, nitric oxide (NO), and 3-nitrotyrosine (3-NT) content were individually measured with the commercial available kits.
Compared with the CON group, Scr and BUN levels significantly increased in the CM group (P < 0.05), and the values in two pre-treatment groups (iNOS + CM and AST + CM) had significantly decreased (P < 0.05). H-E and Tunel staining had shown that renal tubular injury was severe in CM group. The renal injury score and apoptosis index in the two pre-treatment groups also decreased (P < 0.05). The present study showed that in CM group the levels of oxidative stress indicators significantly increased, and the activities of antioxidant stress indicators significantly decreased. These indicators in two pre-treatment groups significantly improved (P < 0.05). In the CM group the expression levels of SITR1 significantly increased, and the ac-p53/p53 significantly increased (P < 0.05). Compared with the CM group, in AST + CM group the expression levels of SIRT1 increased, the expression levels of p53 and ac-p53/p53 decreased (P < 0.05).The levels of NO and 3-NT in CM group significantly increased (P < 0.05). Compared the CM group, the levels in the two pre-treatment groups significantly decreased (P < 0.05).
Astaxanthin has a protective effect on CI-AKI, the mechanism may be related to the SIRT1-p53 pathway. Astaxanthin can reduce the content of NO and 3-NT in renal tissue of CI-AKI, and alleviate the renal injury induced by contrast agents.
本研究旨在进一步探讨虾青素（AST）对大鼠造影剂诱导的急性肾损伤（CI-AKI）的保护作用以及SIRT1-p53信号通路与虾青素之间的关系。
将40只成年雄性Sprague Dawley（SD）大鼠随机分为五组（每组n = 8）：对照组（CON）、接受AST治疗的正常大鼠（AST）、接受造影剂治疗的大鼠（CM）、接受一氧化氮合酶（iNOS）抑制剂异构体治疗的CM大鼠（iNOS + CM）以及接受AST治疗的CM大鼠（AST + CM）。在实验操作后72小时测量血清肌酐（Scr）和血尿素氮（BUN）值。采用苏木精-伊红（H-E）染色观察肾脏的病理变化。采用Tunel染色检测肾小管细胞凋亡。分别使用市售试剂盒测量氧化应激、SIRT1活性、一氧化氮（NO）和3-硝基酪氨酸（3-NT）含量。
与CON组相比，CM组Scr和BUN水平显著升高（P < 0.05），而两个预处理组（iNOS + CM和AST + CM）的值显著降低（P < 0.05）。H-E染色和Tunel染色显示CM组肾小管损伤严重。两个预处理组的肾损伤评分和凋亡指数也降低（P < 0.05）。本研究表明，CM组氧化应激指标水平显著升高，抗氧化应激指标活性显著降低。两个预处理组的这些指标显著改善（P < 0.05）。CM组中SITR1的表达水平显著升高，乙酰化p53/总p53显著升高（P < 0.05）。与CM组相比，AST + CM组中SIRT1的表达水平升高，p53和乙酰化p５3/总p53的表达水平降低（P < 0.05）。CM组中NO和3-NT的水平显著升高（P < 0.05）。与CM组相比，两个预处理组的水平显著降低（P < 0.05）。
虾青素对CI-AKI具有保护作用，其机制可能与SIRT1-p53信号通路有关。虾青素可降低CI-AKI大鼠肾组织中NO和3-NT的含量，减轻造影剂所致的肾损伤。
