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  

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

作　　者：徐辰祺 闵璐琳 陈晓欢 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 顾乐怡[1] XU Chen-qi;MIN Lu-lin;CHEN Xiao-huan;LU Ren-hua;ZHU Ming-li;XIE Ke-wei;QIAN Ying-ying;GUO Xiang-jiang;NI Zhao-hui;AYIJIAKEN Kasimumali;GU Le-yi(Molecular Cell Laboratory for Kidney Diseases,Renal Division,Renji Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200127,China;Department of Vascular Surgery,Renji Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200127,China;Department of Nephrology,Kashgar Second People′s Hospital,Xinjiang Uygur Autonomous Region,Kashgar 844000,China)

机构地区：[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　　处：《上海交通大学学报（医学版）》2018年第3期305-309,共5页Journal of Shanghai Jiao tong University:Medical Science

基　　金：新疆维吾尔自治区自然科学基金(2015211C227)

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。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(non-CKD)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.

关 键 词：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 

分 类 号：R692.5[医药卫生—泌尿科学]