摘要/Abstract
摘要： 目的 · 探讨终末期肾病（end-stage renal disease，ESRD）患者骨骼肌丙酮酸脱氢酶（pyruvate dehydrogenase，PDH）活性及丙酮酸脱氢酶激酶 4（pyruvate dehydrogenase kinase 4，PDK4）在骨骼肌中表达水平的变化。方法 · 收取 ESRD 患者和非慢性肾脏病（non-chronic kidney diseases，non-CKD）患者骨骼肌样本，比较 2 组患者的临床特征，ELISA 法检测 PDH 活性，实时荧光定量 PCR 法检测 PDK1 ～ PDK4 型同工酶、PDH 各亚基的基因转录水平，Western blotting 检测 PDK1 和 PDK4 蛋白表达水平。结果 · non-CKD 组和 ESRD 组患者在一般人口学资料上无明显差异，ESRD 组血浆肌酐、尿素氮显著升高（均 P<0.05），估算的肾小球滤过率、血红蛋白、白蛋白则显著降低（均 P<0.05）。ESRD 组骨骼肌 PDH 活性显著低于 non-CKD 组（P=0.014），2 组患者骨骼肌 PDK1 ～ PDK4 及 PDH 各亚基 mRNA 转录水平无明显差异，ESRD 组 PDK4 蛋白表达量显著高于 non-CKD 对照组（P=0.000）。结论 · ESRD 患者骨骼肌中 PDH 活性下降，可能与 PDK4 表达上调有关。
关键词: &ensp, 终末期肾病；骨骼肌；丙酮酸脱氢酶；丙酮酸脱氢酶激酶 4；线粒体
Abstract:
Objective · To explore the changes of pyruvate dehydrogenase (PDH) activity and pyruvate dehydrogenase kinase 4 (PDK4) expression in the end-stage renal disease (ESRD) patients' skeletal muscles. Methods · Skeletal muscle samples were collected from non-chronic kidney disease (nonCKD) patients and ESRD patients. PDH activity was detected by ELISA assay. Real-time qPCR was performed to examine gene transcription levels of PDK1-PDK4 and PDH subunits. Western blotting analysis was used to detect protein expression levels of PDK1 and PDK4. Results · There were no demographic differences between two groups of patients. Plasma creatinine and urea nitrogen were significantly elevated in ESRD group (both P<0.05), while estimated glomerular filtration rate, hemoglobin and plasma albumin in ESRD group were significantly lower than those in non-CKD group (all P<0.05). Skeletal muscle PDH activity in ESRD group was markedly lower than that in non-CKD group (P=0.014). There were no differences in PDK1- PDK4 and PDH subunits mRNA transcription levels between ESRD and non-CKD group. PDK4 protein expression was significantly higher than that in non-CKD group (P=0.000). Conclusion · The decreased PDH activity in ESRD patients' skeletal muscle may be related to up-regulation of PDK4.
Key words: end-stage renal disease (ESRD), skeletal muscle, pyruvate dehydrogenase (PDH), pyruvate dehydrogenase kinase 4 (PDK4), mitochondria
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