Statins attenuate cholesterol-induced ROS via inhibiting NOX2/NOX4 and mitochondrial pathway in collecting ducts of the kidney.
Statins attenuate cholesterol-induced ROS via inhibiting NOX2/NOX4 and mitochondrial pathway in collecting ducts of the kidney.
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DOI：
10.1186/s12882-022-02815-6
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发表时间：
2022-05-13
期刊：
影响因子：
2.3
通讯作者：
Kong, Yonglun
中科院分区：
文献类型：
--
作者：
Wang, Ani;Lin, Yu;Liang, Baien;Zhao, Xiaoduo;Qiu, Miaojuan;Huang, Hui;Li, Chunling;Wang, Weidong;Kong, Yonglun
他汀类药物治疗主要被推荐用于预防慢性肾脏病患者的心血管风险。他汀类药物也被证明对脂质引起的肾脏疾病有一定的益处。本研究旨在探讨他汀类药物对胆固醇超载所致肾小管损伤的保护作用及其潜在机制。我们使用来自大鼠肾脏的内髓集合管 (IMCD) 细胞和小鼠集合管细胞系 mpkCCD 细胞的管状悬浮液来研究他汀类药物对胆固醇诱导的活性氧 (ROS) 产生的影响。通过蛋白质印迹和 RT-PCR 体外研究以及 5/6 肾切除和高脂肪饮食的大鼠体内 NADPH 氧化酶 2 (NOX2) /NOX4 的蛋白质和 mRNA 表达进行了检查。通过Mito-tracker和JC-1观察线粒体形态和膜电位。他汀类药物治疗与高脂饮食的 5/6Nx 大鼠中 NOX2 和 NOX4 蛋白表达和 mRNA 水平降低相关。他汀类药物治疗显着减少了 IMCD 悬浮液和 mpkCCD 细胞中 ROS 的产生。此外，他汀类药物还可降低胆固醇超载 mpkCCD 细胞中 NOX2 和 NOX4 蛋白表达和 mRNA 水平，并改善线粒体形态和功能。他汀类药物可能通过抑制 NOX 蛋白表达和改善线粒体功能来阻止肾脏中胆固醇诱导的 ROS 产生。他汀类药物可能是治疗肥胖相关肾脏疾病的一种治疗选择。在线版本包含可在 10.1186/s12882-022-02815-6 获取的补充材料。
Statins therapy has been primarily recommended for the prevention of cardiovascular risk in patients with chronic kidney diseases. Statins has also been proved some benefits in lipid-induced kidney diseases. The current study aims to investigate the protection and underlying mechanisms of statins on renal tubular injuries induced by cholesterol overloaded. We used tubular suspensions of inner medullary collecting duct (IMCD) cells from rat kidneys and mouse collecting duct cell line mpkCCD cells to investigate the effect of statins on reactive oxygen species (ROS) production induced by cholesterol. Protein and mRNA expression of NADPH oxidase 2 (NOX2) /NOX4 was examined by Western blot and RT-PCR in vitro studies and in rats with 5/6 nephrectomy and high-fat diet. Mitochondrial morphology and membrane potential was observed by Mito-tracker and JC-1. Statins treatment was associated with decreased NOX2 and NOX4 protein expression and mRNA levels in 5/6Nx rats with high-fat diet. Statins treatment markedly reduced the ROS production in IMCD suspensions and mpkCCD cells. Also, statins reduced NOX2 and NOX4 protein expression and mRNA levels in cholesterol overload mpkCCD cells and improved mitochondrial morphology and function. Statins prevented ROS production induced by cholesterol in the kidney, likely through inhibiting NOXs protein expression and improving mitochondrial function. Statins may be a therapeutic option in treating obesity-associated kidney diseases. The online version contains supplementary material available at 10.1186/s12882-022-02815-6.
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影响因子：
5.6
作者：
Srivastava SP;Kanasaki K;Goodwin JE
通讯作者：
Goodwin JE
管状Mas受体介导脂质诱导的肾损伤
影响因子：
9
作者：
Kong Y;Zhao X;Qiu M;Lin Y;Feng P;Li S;Liang B;Zhu Q;Huang H;Li C;Wang W
通讯作者：
Wang W
DOI：
10.1152/ajprenal.00196.2019
发表时间：
2019-10-01
影响因子：
4.2
作者：
Repetti, Robert L.;Meth, Jennifer;Rohatgi, Rajeev
通讯作者：
Rohatgi, Rajeev
影响因子：
3.2
作者：
Bobulescu IA
通讯作者：
Bobulescu IA
二氢槲皮素通过抑制ROS和NLRP3炎症小体对糖尿病肾病的肾脏保护作用
影响因子：
7.9
作者：
Ding Tao;Wang Shaofei;Mei Xiaobin
通讯作者：
Mei Xiaobin