中国临床药理学与治疗学2017,Vol.22Issue(5):481-489,9.
糖尿病肾病细胞模型三羧酸循环代谢异常和机制初探
Preliminary study on mechanism of tricarboxylic acid cycle disruption in diabetic nephropathy cell model
摘要
Abstract
AIM:To explore the difference of tricarboxylic acid cycle (TCA) intermediates levels between diabetic nephropathy (DN) model cells and normal HK-2 cells and the metabolic disruption of DN model.METHODS:HK-2 cells were cultured in vitro and were divided into normal group,glucose group,palmitic acid (PA) group,PA high glucose group.Kidney cell damage was observed by fluorescence microscopy after mitochondrial staining.Metabolic disruption was evaluated by a GC-MS based metabolomics method.Concentration of TCA intermediates was measured by a GC-MS based quantification method.Expressions of relative enzymes were measured by qPCR method.RESULTS:High glucose did not exert as strong an effect on cell damage or metabolic disruption as PA,which caused obvious cell damage or metabolic disruption in a short period.The combined inducement presented the strongest effect.TCA intermediates variation was the main change in PA caused HK-2 cells metabolic disruption.Further,PA could increase the level of citrate and succinate in HK-2 cells.And instead of SDH in model cell,the increase of succinate level was closely related to succinate-CoA ligase.CONCLUSION:Metabolic disruption of TCA induced by PA may be closely related to diabetic nephropathy.关键词
糖尿病肾病/人肾小管上皮细胞/棕榈酸/琥珀酸Key words
diabetic nephropathy/HK-2/palmitic acid/succinate分类
医药卫生引用本文复制引用
俞晓忆,周芷若,谢媛,孙润彬,费菲,高浩雪,黄京秋,阿基业,王广基..糖尿病肾病细胞模型三羧酸循环代谢异常和机制初探[J].中国临床药理学与治疗学,2017,22(5):481-489,9.基金项目
江苏省科技计划项目临床医学科技专项(BL2014070) (BL2014070)
国家自然科学基金项目(81072692) (81072692)
973“国家重点基础研究发展计划资助”子课题(2012CB517606) (2012CB517606)