Clinical significance study of serum 4-hydroxynonenal, human cartilage glycoprotein-39 and renal injury molecular-1 in the diagnosis of early diabetic nephropathy
YU Shi-ji1 SU Xiao-qing2▲ WANG Gui-liang3 WU Su-zhen4 XIE Yong-li2
1.Gannan Medical University, Jiangxi Province, Ganzhou 341000, China;
2.Department of Endocrinology, Pingxiang People′s Hospital Affiliated to Gannan Medical University, Jiangxi Province, Pingxiang 337000, China;
3.Department of Gastroenterology, Pingxiang People′s Hospital Affiliated to Gannan Medical University, Jiangxi Province, Pingxiang 337000, China;
4.Basic Medical College of Gannan Medical University, Jiangxi Province, Ganzhou 341000, China
Abstract:Objective To investigate the clinical value of serum 4-hydroxynonenal (4-HNE), serum human chondroglycoprotein-39 (YKL-40) and kidney injury molecule 1 (KIM-1) in early renal injury of diabetic nephropathy (DN), and to analyze the correlation of 4-HNE, YKL-40 and KIM-1 with renal injury index, blood glucose and lipid level.Methods A total of 89 patients with type 2 diabetes mellitus (T2DM) hospitalized in the Department of Endocrinology of Pingxiang People′s Hospital from January to July in 2019 were selected, and the patients were divided into normal albuminuria group or only diabetes group (group NA), microalbuminuria group (group MI) and macro albuminuria group(group MA) according to the 24 h urinary protein excretion rate (UAER).In addition, 53 healthy patients in the Physical Examination Department of Pingxiang People′s Hospital were selected as the normal control group (NC).Serum concentrations of 4-HNE, YKL-40 and KIM-1 were determined by enzyme linked immunosorbent assay (ELISA).Results The serum 4-HNE, YKL-40 and KIM-1 in the group MA were higher than those in the group MI, with statistically significant differences (P<0.05).The serum 4-HNE, YKL-40 and KIM-1 in the group MI were higher than those in the group NA, with statistically significant difference (P<0.05).The serum 4-HNE, YKL-40 and KIM-1 in the groups NA, MI and MA were higher than those in the group NC, and the differences were statistically significant (P<0.05).The fasting blood glucose (FPG), glycosylated hemoglobin (HbA1c), serum creatinine (SCr), blood urea nitrogen(BUN), UAER indexes in groups NA, MI MA were higher than those in group NC, with statistically significant differences (P<0.05).Correlation analysis showed that SCR, BUN, Urinary microprotein (UmALB), UAER, FPG and HbA1c were positively correlated with 4-HNE, YKL-40 and KIM-1 (r=0.428, 0.349, 0.390; 0.501, 0.446, 0.491; 0.478, 0.409,0.461; 0.414, 0.502, 0.497; 0.584, 0.558, 0.607; P<0.05).BUN was positively correlated with 4-HNE and YKL-40 (r=0.223, 0.176; P<0.05).Low density lipoprotein (LDL) was negatively correlated with 4-HNE, YKL-40 and KIM-1 (r=-0.169,-0.289,-0.247; P<0.05).Conclusion 4-HNE, YKL-40 and KIM-1 can be used as a sensitive indicator for the early diagnosis of DN, and is expected to provide a basis for the diagnosis of DN in clinical practice.Serum 4-HNE,YKL-40 and KIM-1 are positively correlated with renal injury index and blood glucose level.
余世纪; 苏晓清; 王桂良; 吴素珍; 谢勇丽. 血清4-羟基壬烯醛、人软骨糖蛋白-39、肾损伤分子-1诊断早期糖尿病肾病的临床意义研究[J]. 中国当代医药, 2020, 27(12): 59-62.
YU Shi-ji; SU Xiao-qing; WANG Gui-liang; WU Su-zhen; XIE Yong-li. Clinical significance study of serum 4-hydroxynonenal, human cartilage glycoprotein-39 and renal injury molecular-1 in the diagnosis of early diabetic nephropathy. 中国当代医药, 2020, 27(12): 59-62.
Figueroa-Pérez,Marely G,Pérez-Ramírez,et al.Diabetic nephropathy is ameliorated with peppermint (Mentha piperita)infusions prepared from salicylic acid-elicited plants[J].J Funct Foods,2018,43:55-61.
[2]
Wang M,Wang S,Yao D,et al.A novel long non-coding RNA CYP4B1-PS1-001 regulates proliferation and fibrosis in diabetic nephropathy[J].Mol Cell Endocrinol,2016,426:136-145.
[3]
Bjornstad P,Cherney D,Maahs DM.Early diabetic nephropathy in type 1 diabetes-new insights[J].Curr Opin Endocrinol Diabetes Obes,2014,21(4):279-286.
[4]
Wang J,Wang G,Liang Y,et al.Expression profiling and clinical significance of plasma microRNAs in diabetic nephropathy[J].Diabetes Res,2019,2019:5 204 394.
Han JY,Ma XY,Yu LJ,et al.Correlation between serum YKL-40 levels and albuminuria in type 2 diabetes[J].Genet Mol Res,2015,14(4):18 596-18 603.
[8]
Ramana KV,Srivastava SK,Ansari NH,et al.4-Hydroxynonenal in the pathogenesis and progression of human diseases[J].Curr Med Chem,2014,21(2):230-237.
[9]
Liu G,Ji W,Huang J,et al.4-HNE expression in diabetic rat kidneys and the protective effects of probucol[J].J Endocrinol Invest,2016,39(8):865-873.
[10]
Fritz KS,Galligan JJ,Smathers RL,et al.4-Hydroxynonenal inhibits SIRT3 via thiol-specific modification[J].Chem Res Toxicol,2011,24(5):651-662.
[11]
Chen ZH,Niki E.4-Hydroxynonenal(4-HNE)has been widely accepted as an inducer of oxidative stress.Is this the whole truth about it or can 4-HNE also exert protective effects?[J].IUBMB Life,2010,58(5-6):372-373.
[13]
Rathcke CN,Vestergaard H.YKL-40,a new inflammatory marker with relation to insulin resistance and with a role in endothelial dysfunction and atherosclerosis[J].Inflamm Res,2006,55(6):221-227.
[14]
Malinda KM,Ponce L,Kleinman HK,et al.Gp38k,a protein synthesized by vascular smooth muscle cells,stimulates directional migration of human umbilical vein endothelial cells[J].Exp Cell Res,1999,250(1):168-173.
[15]
Mahdy RA,Nada WM,Hadhoud KM,et al.The role of vascular endothelial growth factor in the progression of diabetic vascular complications[J].Eye(London,England),2010,24(10):1576-1584.
[16]
Ismail OZ,Zhang X,Bonventre JV,et al.G protein α12(Gα12)is a negative regulator of kidney injury molecule-1-mediated efferocytosis[J].AJP Renal Physiology,2015,310(7):607-620.
[17]
Lim AI,Tang SCW,Lai KN,et al.Kidney injury molecule-1:more than just an injury marker of tubular epithelial cells?[J].J Cell Physiol,2013,228(5):917-924.
[18]
Sabbisetti VS,Waikar SS,Antoine DJ,et al.Blood kidney injury molecule-1 is a biomarker of acute and chronic kidney injury and predicts progression to ESRD in type Ⅰdiabetes[J].J Am Soc Nephrol,2014,25(10):2177-2186.