Evaluation of sphingolipid metabolism in the renal cortex of rats with streptozotocin-induced diabetes and the effects of rapamycin
Evaluation of sphingolipid metabolism in the renal cortex of rats with streptozotocin-induced diabetes and the effects of rapamycin
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DOI：
10.1093/ndt/gfq633
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发表时间：
2011-05-01
影响因子：
6.1
通讯作者：
Chen, JiangHua
中科院分区：
文献类型：
--
作者：
Liu, GuangYi;Han, Fei;Chen, JiangHua
背景。脂质代谢异常有助于糖尿病的发病，但尚不确定其是否在糖尿病肾病（DN）的发展中发挥作用。虽然在我们之前的研究中，雷帕霉素被证明可以预防链脲佐菌素 (STZ) 诱导的糖尿病大鼠的 DN 发展，但尚不清楚它是否干预脂质代谢。我们将大鼠分为四组：正常对照大鼠、雷帕霉素治疗的正常大鼠、糖尿病大鼠和雷帕霉素治疗的 DN 大鼠。通过免疫组织化学评估细胞凋亡。从大鼠肾皮质中提取粗脂质和鞘脂，并通过基质辅助激光解吸电离飞行时间质谱法进行分析。采用蛋白质印迹法和免疫组化法检测大鼠肾皮质中鞘脂代谢中的三种关键酶丝氨酸棕榈酰转移酶、酸性鞘磷脂酶和鞘磷脂合酶的表达。结果。糖尿病大鼠的细胞凋亡水平增加，而雷帕霉素治疗可减少细胞凋亡。 STZ 处理通过提高从头合成显着增加了许多鞘脂种类的形成。这些变化受到雷帕霉素治疗的抑制。结论。鞘脂的积累导致 STZ 诱发的糖尿病，雷帕霉素对糖尿病肾病的治疗作用部分是通过抑制鞘脂异常来实现的。
Background. Abnormal lipid metabolism contributes to the pathogenesis of diabetes, but it is uncertain whether it plays a role in the development of diabetic nephropathy (DN). While rapamycin was shown to prevent DN development in streptozotocin (STZ)-induced diabetic rats in our previous studies, it is unknown if it intervenes with lipid metabolism.Methods. We divided the rats into four groups: normal control rats, rapamycin-treated normal rats, diabetic rats and rapamycin-treated DN rats. The apoptosis was evaluated by immunohistochemistry. The crude lipid and sphingolipid were extracted from rat renal cortex and analysed by matrix-assisted laser desorption ionization-time of flight mass spectrometry. The expression of the three key enzymes in sphingolipid metabolism including serine palmitoyltransferase, acid sphingomyelinase and sphingomyelin synthase was measured by western blot and immunohistochemistry in rat renal cortex.Results. The level of apoptosis was increased in diabetic rats, and rapamycin treatment reduced apoptosis. STZ treatment significantly increased formation of many sphingolipids species through elevated de novo synthesis. These changes were inhibited by treatment with rapamycin.Conclusions. Accumulation of sphingolipids contributes to STZ-induced diabetes, and the therapeutic effect of rapamycin on diabetic nephropathy is partly through suppression of sphingolipid abnormality.