Background: Chronic kidney diseases (CKD) are usually associated with dyslipidemia. Statin therapy has been primarily recommended for the prevention of cardiovascular risk in patients with CKD; however, the effects of statins on kidney disease progression remain controversial. This study aims to investigate the effects of statin treatment on renal handling of water in patients and in animals on a high-fat diet./nMethods: Retrospective cohort patient data were reviewed and the protein expression levels of aquaporin-2 (AQP2) and NLRP3 inflammasome adaptor ASC were examined in kidney biopsy specimens. The effects of statins on AQP2 and NLRP3 inflammasome components were examined in nlrp3^-/- mice, 5/6 nephroectomized (5/6Nx) rats with a high-fat diet (HFD), and in vitro./nResults: In the retrospective cohort study, serum cholesterol was negatively correlated to eGFR and AQP2 protein expression in the kidney biopsy specimens. Statins exhibited no effect on eGFR but abolished the negative correlation between cholesterol and AQP2 expression. Whilst nlrp3^+/+ mice showed an increased urine output and a decreased expression of AQP2 protein after a HFD, which was moderately attenuated in nlrp3 deletion mice with HFD. In 5/6Nx rats on a HFD, atorvastatin markedly decreased the urine output and upregulated the protein expression of AQP2. Cholesterol stimulated the protein expression of NLRP3 inflammasome components ASC, caspase-1 and IL-1β, and decreased AQP2 protein abundance in vitro, which was markedly prevented by statins, likely through the enhancement of ASC speck degradation via autophagy./nConclusion: Serum cholesterol level has a negative correlation with AQP2 protein expression in the kidney biopsy specimens of patients. Statins can ameliorate cholesterol-induced inflammation by promoting the degradation of ASC speck, and improve the expression of aquaporin in the kidneys of animals on a HFD.

中文翻译：

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他汀类药物通过抑制肾脏中的NLRP3活化来改善胆固醇诱导的炎症并改善AQP2表达。

背景：慢性肾脏疾病（CKD）通常与血脂异常有关。主要推荐使用他汀类药物治疗来预防CKD患者的心血管风险。但是，他汀类药物对肾脏疾病进展的影响仍存在争议。这项研究的目的是研究他汀类药物治疗对高脂饮食对患者和动物肾脏水处理的影响。/n方法：回顾性研究队列患者的数据，并研究水通道蛋白2（AQP2）和蛋白的表达水平。在肾脏活检标本中检查了NLRP3炎性体衔接子ASC。在nlrp3 ^-/-小鼠，5/6切除高脂饮食（HFD）的5/6肾切除大鼠（5 / 6Nx）的大鼠中，检查了他汀类药物对AQP2和NLRP3炎性小体成分的影响。体外./n结果：在回顾性队列研究中，肾活检标本中血清胆固醇与eGFR和AQP2蛋白表达呈负相关。他汀类药物对eGFR没有影响，但消除了胆固醇与AQP2表达之间的负相关性。尽管nlrp3 ^{+ / +}小鼠在HFD后显示出尿量增加和AQP2蛋白表达降低，但在具有HFD的nlrp3缺失小鼠中被适度减弱。在使用HFD的5 / 6Nx大鼠中，阿托伐他汀显着降低了尿量并上调了AQP2的蛋白表达。胆固醇刺激NLRP3炎性部件ASC，胱天蛋白酶-1和IL-1β的蛋白的表达，并减少AQP2蛋白丰度在体外，他汀类药物可以明显预防这种情况，很可能是通过自噬促进了ASC斑点降解。/n结论：患者肾脏活检标本中的血清胆固醇水平与AQP2蛋白表达呈负相关。他汀类药物可通过促进ASC斑点的降解来改善胆固醇诱发的炎症，并通过HFD改善动物肾脏中水通道蛋白的表达。