上海交通大学学报（医学版）

上海交通大学学报（医学版） ›› 2018, Vol. 38 ›› Issue (3): 305-.doi: 10.3969/j.issn.1674-8115.2018.03.012

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终末期肾病患者骨骼肌中丙酮酸脱氢酶活性与丙酮酸脱氢酶激酶 4 的表达

徐辰祺 1*，闵璐琳 1*，陈晓欢 3 ，陆任华 1 ，朱铭力 1 ，谢可炜 1 ，钱盈盈 1 ，郭相江 2 ，倪兆慧 1 ，阿依加肯·卡司木马力 3#，顾乐怡 1#   

  1. 1. 上海交通大学 医学院附属仁济医院肾脏科，分子细胞（肾病）实验室，上海 200127；2. 上海交通大学 医学院附属仁济医院血管外科，上海 200127；3. 新疆维吾尔自治区喀什地区第二人民医院肾病科，喀什 844000
  • 出版日期:2018-03-28 发布日期:2018-05-03
  • 通讯作者: ?顾乐怡，电子信箱：guleyi@aliyun.com。阿依加肯·卡司木马力，电子信箱：15809042291@163.com。# 为共同通信作者。
  • 作者简介:徐辰祺（1988—），男，博士生；电子信箱：chenqi_xu_nephro@hotmail.com。闵璐琳（1985—），女，住院医师，硕士；电子信箱：lulin0311019@hotmail.com。* 为共同第一作者。
  • 基金资助:
    新疆维吾尔自治区自然科学基金（2015211C227)

Pyruvate dehydrogenase activity and pyruvate dehydrogenase kinase 4 expression in skeletal muscle of end-stage renal disease patients

XU Chen-qi1* , MIN Lu-lin1* , CHEN Xiao-huan3 , LU Ren-hua1 , ZHU Ming-li1 , XIE Ke-wei1 , QIAN Ying-ying1 , GUO Xiang-jiang2 , NI Zhao-hui1 , AYIJIAKEN Kasimumali3#, GU Le-yi1#   

  1. 1. Molecular Cell Laboratory for Kidney Diseases, Renal Division, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China; 2. Department of Vascular Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China; 3. Department of Nephrology, Kashgar Second People′s Hospital, Xinjiang Uygur Autonomous Region, Kashgar 844000, China
  • Online:2018-03-28 Published:2018-05-03
  • Supported by:
     Natural Science Foundation of Xinjiang Uygur Autonomous Region，2015211C227

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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