Division of Nephrology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Am J Nephrol. 2020;51(5):381-389. doi: 10.1159/000506729. Epub 2020 Mar 6.
Autoclaving rodent diets is common in laboratory animals, but autoclaving increases the formation of dietary advanced glycation end-products (AGE). We studied the effect of autoclaved (AC) diet alone or in combination with a diet high in bioavailable phosphorus on biochemistries of chronic kidney disease-mineral and bone disorder (CKD-MBD), intestinal gene expression, and oxidative stress.
Male CKD rats (Cy/+) and normal littermates were fed 1 of 3 diets: AC 0.7% phosphorus grain-based diet for 28 weeks (AC); AC diet for 17 weeks followed by non-autoclaved (Non-AC) 0.7% phosphorus casein diet until 28 weeks (AC + Casein); or Non-AC diet for 16 weeks followed by a Non-AC purified diet until 30 weeks (Non-AC + Casein).
AC diets contained ~3× higher AGEs and levels varied depending on the location within the autoclave. Rats fed the AC and AC + Casein diets had higher total AGEs and oxidative stress, irrespective of kidney function. Kidney function was more severely compromised in CKD rats fed AC or AC + Casein compared to Non-AC + Casein. There was a disease-by-diet interaction for plasma phosphorus, parathyroid hormone, and c-terminal fibroblast growth factor-23, driven by high values in the CKD rats fed the AC + Casein diet. Compared to Non-AC + Casein, AC and AC + Casein-fed groups had increased expression of receptor of AGEs and intestinal NADPH oxidase dual oxidase-2, independent of kidney function.
Autoclaving rodent diets impacts the progression of CKD and CKD-MBD, highlighting the critical importance of standardizing diets in experiments.
在实验动物中，高压蒸汽灭菌处理啮齿动物饲料很常见，但高压蒸汽灭菌会增加饮食中晚期糖基化终产物（AGE）的形成。我们研究了单独使用高压蒸汽灭菌（AC）饲料或与高生物可利用磷饮食联合使用对慢性肾脏病-矿物质和骨异常（CKD-MBD）的生化指标、肠道基因表达和氧化应激的影响。
雄性 CKD 大鼠（Cy/+）和正常同窝仔鼠分别喂食 3 种饮食中的 1 种：28 周的 AC 0.7%磷谷物基础饮食（AC）；17 周的 AC 饮食后，改为非高压蒸汽灭菌（Non-AC）0.7%磷酪蛋白饮食直至 28 周（AC+Casein）；或 16 周的 Non-AC 饮食后，改为 Non-AC 纯化饮食直至 30 周（Non-AC+Casein）。
AC 饮食含有~3 倍的 AGE，其水平取决于高压蒸汽灭菌器内的位置。无论肾功能如何，喂食 AC 和 AC+Casein 饮食的大鼠总 AGE 和氧化应激水平均较高。与喂食 Non-AC+Casein 的 CKD 大鼠相比，喂食 AC 或 AC+Casein 的大鼠的肾功能受损更为严重。由于 CKD 大鼠喂食 AC+Casein 饮食时，其血浆磷、甲状旁腺激素和 C 端成纤维细胞生长因子-23 值较高，导致了疾病与饮食之间存在交互作用。与 Non-AC+Casein 相比，AC 和 AC+Casein 饮食组的 AGE 受体和肠道 NADPH 氧化酶双氧化酶-2 的表达增加，与肾功能无关。
高压蒸汽灭菌处理啮齿动物饲料会影响 CKD 和 CKD-MBD 的进展，突出了在实验中标准化饮食的重要性。
