他汀类药物通过抑制肾脏集合管中的 NOX2/NOX4 和线粒体途径来减轻胆固醇诱导的 ROS。
Statins attenuate cholesterol-induced ROS via inhibiting NOX2/NOX4 and mitochondrial pathway in collecting ducts of the kidney.
机构信息
Cardiovascular Center, The 5thAffiliated Hospital, Sun Yat-Sen University, Zhuhai, 519000, China.
Department of Pathology, Zhujiang Hospitial, Southern Medical University, Guangzhou, 510282, China.
出版信息
BMC Nephrol. 2022 May 13;23(1):184. doi: 10.1186/s12882-022-02815-6.
BACKGROUND
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.
METHODS
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.
RESULTS
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.
CONCLUSION
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.
背景
他汀类药物治疗主要推荐用于预防慢性肾脏病患者的心血管风险。他汀类药物在脂质诱导的肾脏疾病中也被证明有一些益处。本研究旨在探讨他汀类药物对胆固醇超负荷诱导的肾小管损伤的保护作用及其潜在机制。
方法
我们使用来自大鼠肾脏的髓质内集合管（IMCD）细胞的管状悬浮液和小鼠集合管细胞系 mpkCCD 细胞，研究他汀类药物对胆固醇诱导的活性氧（ROS）产生的影响。体外研究和 5/6 肾切除和高脂肪饮食的大鼠中，通过 Western blot 和 RT-PCR 检测 NADPH 氧化酶 2（NOX2）/NOX4 的蛋白和 mRNA 表达。通过 Mito-tracker 和 JC-1 观察线粒体形态和膜电位。
结果
他汀类药物治疗与高脂肪饮食 5/6Nx 大鼠中 NOX2 和 NOX4 蛋白表达和 mRNA 水平降低有关。他汀类药物治疗明显减少了 IMCD 悬浮液和 mpkCCD 细胞中的 ROS 产生。此外，他汀类药物降低了胆固醇超负荷 mpkCCD 细胞中 NOX2 和 NOX4 的蛋白表达和 mRNA 水平，并改善了线粒体形态和功能。
结论
他汀类药物可预防肾脏中胆固醇诱导的 ROS 产生，可能通过抑制 NOXs 蛋白表达和改善线粒体功能。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。
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