伴微量白蛋白尿2型糖尿病患者血清脂肪细胞型脂肪酸结合蛋白和4和第10号染色体缺失的磷酸酶张力蛋白同源物蛋白的研究
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摘要
目的探讨2型糖尿病(T2DM)伴微量白蛋白尿患者血清脂肪细胞型脂肪酸结合蛋白(FABP4)和第10号染色体缺失的磷酸酶和张力蛋白同源物(PTEN)蛋白表达水平变化及两者在糖尿病肾病(DN)发生过程中的相互关系。方法收集T2DM患者120例,据尿白蛋白肌酐比值(UACR)进行分组,其中正常白蛋白尿组(D0)39例,微量白蛋白尿组(D1)81例。同时收集39例正常对照组(NC)。采用ELI-SA法检测受试者外周血清FABP4和PTEN蛋白表达的水平。结果 T2DM组血清FABP4和PTEN蛋白水平均显著高于正常对照组(P <0.001)。D1组血清FABP4和PTEN蛋白水平显著高于NC组及D0组(均P <0.05)。T2DM患者中,Log(FABP4)与PTEN蛋白(r=0.524,P <0.001)、Log(UACR)(r=0.202,P <0.05)均呈正相关。二分类Logistic回归分析显示,血清FABP4水平与T2DM患者尿微量白蛋白的出现独立相关(OR=1.147,95%CI∶1.042～1.263,P=0.005)。结论血清FABP4水平也许可作为DN患者的早期预测指标。FABP4和PTEN蛋白可能在DN的发生中存在着相互联系。
Objective To investigate the changes of serum fatty acid-binding protein 4(FABP4)and phosphatase and tensin homology deleted on chromosome ten(PTEN)protein expression in the type 2 diabetes mellitus(T2DM)patients with microalbuminuria,and to explore the correlation between FABP4 and PTEN in the onset of diabetic nephropathy(DN).Methods120 T2DM patients and 39 healthy subjects were enrolled in this study.The patients were divided into two groups according to urinary albumin creatinine ratio(UACR):39 diabetes mellitus without microalbuminuria(D0)cases and 81 diabetes mellitus with microalbuminuria(D1)cases.The serum FABP4 and PTEN protein expression level of the subjects were detected with enzyme-linked immunosorbent assay(ELISA).ResultsThe patients with T2DM showed high FABP4 and PTEN protein expression levels compared to normal control group(P<0.001).The serum levels of FABP4 and PTEN protein expression in diabetes mellitus patients with microalbuminuria were all significantly higher than those in the normal control group and the diabetes mellitus without microalbuminuria(P<0.05).In type 2 diabetes mellitus patients,Log FABP4 correlated positively with PTEN protein(r=0.524,P<0.001)and Log UACR(r=0.202,P<0.05).Binary logistic regressions showed that serum FABP4 level was independently associated with the occurrence of microalbuminuria in T2DM patients(OR=1.156,95%CI=1.062-1.258,P=0.001).Conclusion The serum levels of FABP4 might be considered to be the earlier markers in the onset of DN.There might be correlation between FABP4 and PTEN protein in the occurrence of DN.
Objective To investigate the changes of serum fatty acid-binding protein 4(FABP4)and phosphatase and tensin homology deleted on chromosome ten(PTEN)protein expression in the type 2 diabetes mellitus(T2DM)patients with microalbuminuria,and to explore the correlation between FABP4 and PTEN in the onset of diabetic nephropathy(DN).Methods120 T2DM patients and 39 healthy subjects were enrolled in this study.The patients were divided into two groups according to urinary albumin creatinine ratio(UACR):39 diabetes mellitus without microalbuminuria(D0)cases and 81 diabetes mellitus with microalbuminuria(D1)cases.The serum FABP4 and PTEN protein expression level of the subjects were detected with enzyme-linked immunosorbent assay(ELISA).ResultsThe patients with T2DM showed high FABP4 and PTEN protein expression levels compared to normal control group(P<0.001).The serum levels of FABP4 and PTEN protein expression in diabetes mellitus patients with microalbuminuria were all significantly higher than those in the normal control group and the diabetes mellitus without microalbuminuria(P<0.05).In type 2 diabetes mellitus patients,Log FABP4 correlated positively with PTEN protein(r=0.524,P<0.001)and Log UACR(r=0.202,P<0.05).Binary logistic regressions showed that serum FABP4 level was independently associated with the occurrence of microalbuminuria in T2DM patients(OR=1.156,95%CI=1.062-1.258,P=0.001).Conclusion The serum levels of FABP4 might be considered to be the earlier markers in the onset of DN.There might be correlation between FABP4 and PTEN protein in the occurrence of DN.
引文
[1]王华,张浩军,赵婷婷,等.糖尿病肾病ETFβ表达变化与脂毒性关系研究[J].中国比较医学杂志,2015,25(5):5-8.
[2]DEY N,BERA A,DAS F,et al.High glucose enhances microR-NA-26a to activate mTORC1 for mesangial cell hypertrophy and matrix protein expression[J].Cell Signal,2015,27(7):1276-1285.
[3]SU D,ZHANG C L,GAO Y C,et al.Gene Expression and correlation of pten and fabp4 in liver,muscle,and adipose tissues of type 2 diabetes rats[J].Med Sci Monit,2015,21:3616-3621.
[4]LI Y Y,XIAO R,LI C P,et al.Increased plasma levels of FABP4and PTEN is associated with more severe insulin resistance in women with gestational diabetes mellitus[J].Med Sci Monit,2015,21:426-431.
[5]ZHAN M,USMAN I M,SUN L,et al.Disruption of renal tubular mitochondrial quality control by Myo-inositol oxygenase in diabetic kidney disease[J].J Am Soc Nephrol,2015,26(6):1304-1321.
[6]MCCLELLAND A D,HERMAN-EDELSTEIN M,KOMERS R,et al.miR-21 promotes renal fibrosis in diabetic nephropathy by targeting PTEN and SMAD7[J].Clin Sci(Lond),2015,129(12):1237-1249.
[7]SANGHAVI M,VAJIR M,KUMAR S,et al.NFAT inhibitor tributyl hexadecyl phosphonium bromide,ameliorates high fructose induced insulin resistance and nephropathy[J].Chem Biol Interact,2015,240:268-277.
[8]SANTAMARIA B,MARQUEZ E,LAY A,et al.IRS2 and PTEN are key molecules in controlling insulin sensitivity in podocyte[sJ].Biochim BiophysActa,2015,1853(12):3224-3234.
[9]邢玲玲.PI3K/Akt通路在糖尿病肾病足细胞损伤中的作用[D].河北石家庄:河北医科大学,2012.
[10]邢玲玲,傅淑霞,杨林,等.PTEN在糖尿病肾病患者足细胞损伤中的作用[J].临床与实验病理学杂志,2014,30(12):1375-1378.
[11]KRALISCH S,STEPAN H,KRATZSCH J,et al.Serum levels of adipocyte fatty acid binding protein are increased in gestational diabetes mellitus[J].Eur J Endocrinol,2009,160(1):33-38.
[12]吴迁,王海燕.脂肪细胞脂肪酸结合蛋白与糖尿病肾病早期的相关性研究[J].中国实用医药,2011,6(5):1-2.
[13]ARAGONèS G,SAAVEDRA P,HERAS M,et al.Fatty acidbinding protein 4 impairs the insulin-dependent nitric oxide pathway in vascular endothelial cells[J].Cardiovasc Diabetol,2012,11:72.
[14]XING L,LIU Q,FU S,et al.PTEN Inhibits High Glucose-Induced Phenotypic Transition in Podocytes[J].J Cell Biochem,2015,116(8):1776-1784.
[15]LIU L,HU X,CAI G Y,et al.High glucose-induced hypertrophy of mesangial cells is reversed by connexin43 overexpression via PTEN/Akt/mTOR signaling[J].Nephrol Dial Transplant,2012,27(1):90-100.
[16]ZHU L,ZHAO S,LIU S,et al.PTEN Regulates Renal Extracellular Matrix Deposit via Increased CTGF in Diabetes Mellitus[J].JCell Biochem,2016,117(5):1187-1198.
[17]SHEMESH I I,ROZEN-ZVI B,KALECHMAN Y,et al.AS101prevents diabetic nephropathy progression and mesangial cell dysfunction:regulation of the AKT downstream pathway[J].PLoS One,2014,9(12):e114287.
[18]章娜,刘琳,严宗逊.血浆脂肪细胞型脂肪酸结合蛋白与2型糖尿病患者慢性肾脏病的相关性研究[J].四川医学,2016,7(37):760-763.
[19]NI X,GU Y,YU H,et al.Serum adipocyte fatty acid-binding protein 4 levels are independently associated with radioisotope glomerular filtration rate in type 2 diabetic patients with early diabetic nephropathy[J].Biomed Res Int,2018,2018:4578140.
[20]皇甫建,徐焱成,李彩萍,等.糖调节受损及初发2型糖尿病患者外周血脂肪细胞型脂肪酸结合蛋白4及人第10号染色体缺失的磷酸酶及张力蛋白同源物水平变化及与胰岛素抵抗的相关性[J].中华糖尿病杂志,2014,6(9):660-664.
[21]NAKAMURA R,OKURA T,FUJIOKA Y,et al.Serum fatty acid-binding protein 4(FABP4)concentration is associated with insulin resistance in peripheral tissues,A clinical study[J].PLoSOne,2017,12(6):e0179737.
[2]DEY N,BERA A,DAS F,et al.High glucose enhances microR-NA-26a to activate mTORC1 for mesangial cell hypertrophy and matrix protein expression[J].Cell Signal,2015,27(7):1276-1285.
[3]SU D,ZHANG C L,GAO Y C,et al.Gene Expression and correlation of pten and fabp4 in liver,muscle,and adipose tissues of type 2 diabetes rats[J].Med Sci Monit,2015,21:3616-3621.
[4]LI Y Y,XIAO R,LI C P,et al.Increased plasma levels of FABP4and PTEN is associated with more severe insulin resistance in women with gestational diabetes mellitus[J].Med Sci Monit,2015,21:426-431.
[5]ZHAN M,USMAN I M,SUN L,et al.Disruption of renal tubular mitochondrial quality control by Myo-inositol oxygenase in diabetic kidney disease[J].J Am Soc Nephrol,2015,26(6):1304-1321.
[6]MCCLELLAND A D,HERMAN-EDELSTEIN M,KOMERS R,et al.miR-21 promotes renal fibrosis in diabetic nephropathy by targeting PTEN and SMAD7[J].Clin Sci(Lond),2015,129(12):1237-1249.
[7]SANGHAVI M,VAJIR M,KUMAR S,et al.NFAT inhibitor tributyl hexadecyl phosphonium bromide,ameliorates high fructose induced insulin resistance and nephropathy[J].Chem Biol Interact,2015,240:268-277.
[8]SANTAMARIA B,MARQUEZ E,LAY A,et al.IRS2 and PTEN are key molecules in controlling insulin sensitivity in podocyte[sJ].Biochim BiophysActa,2015,1853(12):3224-3234.
[9]邢玲玲.PI3K/Akt通路在糖尿病肾病足细胞损伤中的作用[D].河北石家庄:河北医科大学,2012.
[10]邢玲玲,傅淑霞,杨林,等.PTEN在糖尿病肾病患者足细胞损伤中的作用[J].临床与实验病理学杂志,2014,30(12):1375-1378.
[11]KRALISCH S,STEPAN H,KRATZSCH J,et al.Serum levels of adipocyte fatty acid binding protein are increased in gestational diabetes mellitus[J].Eur J Endocrinol,2009,160(1):33-38.
[12]吴迁,王海燕.脂肪细胞脂肪酸结合蛋白与糖尿病肾病早期的相关性研究[J].中国实用医药,2011,6(5):1-2.
[13]ARAGONèS G,SAAVEDRA P,HERAS M,et al.Fatty acidbinding protein 4 impairs the insulin-dependent nitric oxide pathway in vascular endothelial cells[J].Cardiovasc Diabetol,2012,11:72.
[14]XING L,LIU Q,FU S,et al.PTEN Inhibits High Glucose-Induced Phenotypic Transition in Podocytes[J].J Cell Biochem,2015,116(8):1776-1784.
[15]LIU L,HU X,CAI G Y,et al.High glucose-induced hypertrophy of mesangial cells is reversed by connexin43 overexpression via PTEN/Akt/mTOR signaling[J].Nephrol Dial Transplant,2012,27(1):90-100.
[16]ZHU L,ZHAO S,LIU S,et al.PTEN Regulates Renal Extracellular Matrix Deposit via Increased CTGF in Diabetes Mellitus[J].JCell Biochem,2016,117(5):1187-1198.
[17]SHEMESH I I,ROZEN-ZVI B,KALECHMAN Y,et al.AS101prevents diabetic nephropathy progression and mesangial cell dysfunction:regulation of the AKT downstream pathway[J].PLoS One,2014,9(12):e114287.
[18]章娜,刘琳,严宗逊.血浆脂肪细胞型脂肪酸结合蛋白与2型糖尿病患者慢性肾脏病的相关性研究[J].四川医学,2016,7(37):760-763.
[19]NI X,GU Y,YU H,et al.Serum adipocyte fatty acid-binding protein 4 levels are independently associated with radioisotope glomerular filtration rate in type 2 diabetic patients with early diabetic nephropathy[J].Biomed Res Int,2018,2018:4578140.
[20]皇甫建,徐焱成,李彩萍,等.糖调节受损及初发2型糖尿病患者外周血脂肪细胞型脂肪酸结合蛋白4及人第10号染色体缺失的磷酸酶及张力蛋白同源物水平变化及与胰岛素抵抗的相关性[J].中华糖尿病杂志,2014,6(9):660-664.
[21]NAKAMURA R,OKURA T,FUJIOKA Y,et al.Serum fatty acid-binding protein 4(FABP4)concentration is associated with insulin resistance in peripheral tissues,A clinical study[J].PLoSOne,2017,12(6):e0179737.
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