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糖尿病肾病细胞模型三羧酸循环代谢异常和机制初探

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

中国临床药理学与治疗学2017,Vol.22Issue(5):481-489,9.
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

俞晓忆 1周芷若 2谢媛 1孙润彬 1费菲 1高浩雪 1黄京秋 1阿基业 1王广基1

作者信息

  • 1. 中国药科大学药科院药物代谢动力学重点实验室,南京210046,江苏
  • 2. 南京中医药大学药学院药效与安全性评价重点实验室,南京210023,江苏
  • 折叠

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)

中国临床药理学与治疗学

OACSCDCSTPCD

1009-2501

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