Department for BioMedical Research (DBMR), University of Bern, 3010 Bern, Switzerland.
Department of Nephrology and Hypertension, Inselspital, Bern University Hospital, University of Bern, 3010 Bern, Switzerland.
Biomolecules. 2022 Aug 19;12(8):1147. doi: 10.3390/biom12081147.
Cardiovascular events are the main cause of death in patients with chronic kidney disease. We hypothesize that the protective effects of renal cholesterol and vitamin D metabolism are lost under this condition. Nephropathy was induced by adenine in Apolipoprotein E knockout mice. The atherosclerotic phenotype was compared to mice with normal renal function.
Mice were fed a western diet ±0.15% adenine. Urine and feces were collected to assess renal function and fecal output. Atherosclerosis, serum lipoprotein composition and functionality, hepatic lipids, and expression of genes involved in lipid metabolism, vitamin D and Na homeostasis, were assessed. Bones were analyzed by microCT.
Mice fed with adenine showed enhanced urinary Na, Ca, and Pi excretion, reduced urinary pH, Urea/Urea, and Creatinine/Creatinine ratios. They developed less atherosclerosis. Lipoproteins in serum and hepatic lipids remained unchanged. Cholesterol efflux increased. Fecal output of cholesteryl ester and triglycerides increased. In the liver, mRNA levels of , , and increased; in the kidneys, , , and decreased. Adenine increased cholesterol efflux in vitro. Tibias were shorter.
Adenine induced tubular damage and was athero-protective because of enhanced cholesterol efflux and lipids elimination in feces. Bone growth was also affected.
心血管事件是慢性肾脏病患者死亡的主要原因。我们假设在这种情况下，肾脏胆固醇和维生素 D 代谢的保护作用会丧失。载脂蛋白 E 基因敲除小鼠通过腺嘌呤诱导发生肾病。将动脉粥样硬化表型与肾功能正常的小鼠进行比较。
用含或不含 0.15%腺嘌呤的西方饮食喂养小鼠。收集尿液和粪便以评估肾功能和粪便排出量。评估动脉粥样硬化、血清脂蛋白组成和功能、肝脂质以及参与脂质代谢、维生素 D 和钠稳态的基因的表达。通过 microCT 分析骨骼。
喂食腺嘌呤的小鼠表现出增强的尿钠、钙和磷排泄，降低的尿 pH 值、尿素/尿素和肌酐/肌酐比值。它们的动脉粥样硬化程度较低。血清中的脂蛋白和肝脂质保持不变。胆固醇外排增加。胆甾醇酯和甘油三酯的粪便排出量增加。在肝脏中，mRNA 水平增加；在肾脏中，mRNA 水平降低。腺嘌呤增加了体外胆固醇外排。胫骨变短。
腺嘌呤诱导肾小管损伤，并通过增强胆固醇外排和粪便中脂质的消除而具有抗动脉粥样硬化作用。骨生长也受到影响。
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