Diabetic nephropathy induces alterations in the glomerular and tubule lipid profiles
Diabetic nephropathy induces alterations in the glomerular and tubule lipid profiles
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DOI：
10.1194/jlr.m049189
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发表时间：
2014-07-01
影响因子：
6.5
通讯作者：
Caprioli, Richard M.
中科院分区：
文献类型：
--
作者：
Grove, Kerri J.;Voziyan, Paul A.;Caprioli, Richard M.
糖尿病肾病（diabetic nephropathy，DN）是糖尿病的主要并发症之一。肾脏病变影响肾小球和肾小管，但其发病机制尚未完全清楚。磷脂和糖脂是在健康和疾病中执行多种细胞功能的分子，它们在DN发病机制中的作用尚不清楚。我们采用高空间分辨率MALDI成像MS来确定eNOS（-/-）db/db小鼠肾脏中的脂质变化，eNOS（-/-）db/db小鼠是DN的稳健模型。在不干扰组织形态的情况下，在单个肾小球和肾小管中测定磷脂和糖脂结构、定位模式和相对组织水平。来自四种不同类别的特定肾小球和肾小管脂质种类的水平显著增加，即，与非糖尿病对照组相比，在糖尿病肾脏中检测到神经节苷脂、磺基糖鞘脂、溶血磷脂和磷脂酰乙醇胺。非酶氧化和糖氧化途径的抑制减弱了脂质水平的升高，并改善了肾脏病理，即使血糖水平保持不变。我们的数据表明，肾小球和/或肾小管中特异性磷酸脂和糖脂的水平与糖尿病肾脏病理学相关。我们认为，高血糖诱导的DN的致病机制需要中间氧化步骤，涉及特定的磷脂和糖脂物种。
Diabetic nephropathy (DN) is a major life-threatening complication of diabetes. Renal lesions affect glomeruli and tubules, but the pathogenesis is not completely understood. Phospholipids and glycolipids are molecules that carry out multiple cell functions in health and disease, and their role in DN pathogenesis is unknown. We employed high spatial resolution MALDI imaging MS to determine lipid changes in kidneys of eNOS(-/-) db/db mice, a robust model of DN. Phospholipid and glycolipid structures, localization patterns, and relative tissue levels were determined in individual renal glomeruli and tubules without disturbing tissue morphology. A significant increase in the levels of specific glomerular and tubular lipid species from four different classes, i.e., gangliosides, sulfoglycosphingolipids, lysophospholipids, and phosphatidylethanolamines, was detected in diabetic kidneys compared with nondiabetic controls. Inhibition of nonenzymatic oxidative and glycoxidative pathways attenuated the increase in lipid levels and ameliorated renal pathology, even though blood glucose levels remained unchanged. Our data demonstrate that the levels of specific phospho-and glycolipids in glomeruli and/or tubules are associated with diabetic renal pathology. We suggest that hyperglycemia-induced DN pathogenic mechanisms require intermediate oxidative steps that involve specific phospholipid and glycolipid species.