Klotho、TXNIP在老年糖尿病心肌病中的表达及其临床意义

doi:10.3969/j.issn.1003-9198.2021.05.010

摘要/Abstract

摘要： 目的探讨血清硫氧还蛋白相互作用蛋白(TXNIP)、Klotho表达水平与老年糖尿病心肌病(DCM)的相关性。方法选取2018年5月至2020年3月期间于本院就诊的67例老年DCM病人为DCM组;选取同期住院及门诊的老年DM无心肌病病人72例作为DM组,同期老年健康体检者84例作为对照组。检测3组血清Klotho mRNA、TXNIP水平,并分析其与血清肌钙蛋白I(cTnI)、基质金属蛋白酶组织抑制因子-1(TIMP-1)、心钠素(ANP)、基质金属蛋白酶-2(MMP-2)水平的相关性及发生DCM的影响因素。结果 DCM组血清TXNIP、BNP、cTnI、TIMP-1、ANP水平高于DM组和对照组,Klotho mRNA、MMP-2水平低于DM组和对照组(P＜0.05)。DCM病人血清Klotho mRNA与TXNIP呈负相关(r=-0.646,P＜0.05);Klotho mRNA(TXNIP)与MMP-2呈正(负)相关(P＜0.05),与BNP、cTnI、TIMP-1、ANP呈负(正)相关(P＜0.05)。Logistic 回归结果显示,TXNIP、ANP是影响DM病人发生心肌病的独立危险因素(P＜0.05),Klotho mRNA是影响DM病人发生心肌病的保护因素(P＜0.05)。结论 DCM病人中血清TXNIP呈高表达、Klotho呈低表达,对于临床应用可能有较高的参考价值。

关键词: 糖尿病心肌病, 硫氧还蛋白相互作用蛋白, Klotho

Abstract: Objective To explore the correlation between the levels of serum thioredoxin-interacting protein (TXNIP) and Klotho and diabetic cardiomyopathy(DCM) in the elderly. Methods From May 2018 to March 2020, 67 elderly patients with DCM were selected as DCM group; At the same time, 72 elderly patients with diabetic mellitus (DM) without cardiomyopathy were selected as DM group, in addition, 84 cases of elderly healthy people were treated as normal control group. The expression of Klotho mRNA was detected by real-time fluorescence quantitative PCR (qRT-PCR); The level of serum TXNIP was detected by enzyme-linked immunosorbent assay (ELISA); The correlation between the levels of serum Klotho mRNA, TXNIP and serum parameters in the patients with DCM was analyzed, and the influencing factors of DCM were analyzed by Logistic regression. Results The levels of serum TXNIP, brain natriuretic peptide (BNP), cardiac troponin I (cTnI), tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), atrial natriuretic peptide (ANP) in DCM group were higher than those in DM group and normal control group, and the levels of Klotho mRNA and matrix metalloproteinase-2 (MMP-2) were lower than these in DM group and normal control group (P<0.05). There was a negative correlation between serum Klotho mRNA and TXNIP in the patients with DCM (r=-0.646, P<0.05); Klotho mRNA (TXNIP) was positively (negatively) correlated with MMP-2 (P < 0.05), and negatively (positively) correlated with BNP, cTnI, TIMP-1 and ANP (P < 0.05). Logistic regression showed that TXNIP and ANP were the independent risk factors of DCM (P < 0.05), and Klotho mRNA was the protective factor of DCM (P < 0.05). Conclusions TXNIP is highly expressed in the serum of the patients with DCM, while Klotho is lowly expressed, which may have a high reference value for clinical application.

Key words: diabetic cardiomyopathy, serum, thioredoxin-interacting protein, Klotho

中图分类号:

R 587.2

伊芬秀. Klotho、TXNIP在老年糖尿病心肌病中的表达及其临床意义[J]. 实用老年医学, 2021, 35(5): 470-474.

YI Fen-xiu. Expressions and clinical significance of Klotho and TXNIP in the elderly with diabetic cardiomyopathy[J]. Practical Geriatrics, 2021, 35(5): 470-474.

参考文献

[1] ZHOU H, YUE Y, WANG J, et al. Melatonin therapy for diabetic cardiomyopathy: a mechanism involving Syk-mitochondrial complex I-SERCA pathway[J]. Cell Signal, 2018, 47(1):88-100.
[2] 迟庆杰, 王天乐, 祁荣兴. 糖尿病心肌病影像诊断研究进展[J]. 中国临床医学, 2018, 25(5):129-134.
[3] 李莎莎, 郁丽霞, 何敖林, 等. 分泌型Klotho作为慢性肾脏病患者血清学标志物的可行性研究进展[J]. 中华肾脏病杂志, 2018, 34(12):956-960.
[4] GATEVA A T, ASSYOV Y S, VELIKOVA T, et al. Higher levels of thioredoxin interacting protein (TXNIP) in patients with prediabetes compared to obese normoglycemic subjects[J]. Diabetes Metab Syndr, 2019, 13(1):734-737.
[5] 应令雯, 周健. 2017年ADA糖尿病医学诊疗标准解读[J]. 中国医学前沿杂志:电子版, 2017, 9(1):48-55.
[6] VAN-STEEN S C, WOODWARD M, CHALMERS J, et al. Haemoglobin glycation index and risk for diabetes-related complications in the action in diabetes and vascular disease: Preterax and diamicron modified release controlled evaluation (ADVANCE) trial[J]. Diabetologia, 2018, 61(4):780-789.
[7] 田静, 吕嵘, 郭炜. 线粒体障碍在糖尿病性心肌病中的作用及中医药研究进展[J]. 中国中药杂志, 2018, 43(1):8-14.
[8] CUI W, LENG B, WANG G P. Klotho protein inhibits H2O2-induced oxidative injury in endothelial Cells via regulation of PI3K/Akt/Nrf2/HO-1 Pathways[J]. Can J Physiol Pharmacol, 2019, 97(5):370-376.
[9] 木尼热·提力瓦力迪, 周萍, 王顺, 等. Klotho蛋白对缺血-再灌注肾损伤大鼠氧化应激的影响[J]. 肾脏病与透析肾移植杂志, 2019, 28(1):36-40.
[10]刘洪, 冯小兰, 袁晓玲, 等. 糖尿病患者血清sKlotho、NGAL、MCP-1和TGF-β1的表达及意义[J]. 河北医药, 2019, 41(2):186-189.
[11]申甚莉, 刘建辉. Txnip与胰腺β细胞功能障碍和细胞凋亡[J]. 中国现代应用药学, 2018, 35(6):933-936.
[12]WANG X, HUANG H, SU C, et al. Cilostazol ameliorates high free fatty acid (FFA)-induced activation of NLRP3 inflammasome in human vascular endothelial cells[J]. Artificial Cells, 2019, 47(1):3704-3710.
[13]刘敏洁, 薛现军, 姜蕾, 等. Trx、Txnip和CysC与糖尿病肾病的相关性[J]. 实验与检验医学, 2019, 37(4):710-712.
[14]李伟真, 丛莎莎, 高翔. 血清脑钠肽检测在糖尿病心肌病早期诊断中的应用价值[J]. 糖尿病新世界, 2018, 21(6):50-51.
[15]ANTONOV I B, KOZLOV K L, PAL’TSEVA E M, et al. Matrix metalloproteinases MMP-1 and MMP-9 and their inhibitor TIMP-1 as markers of dilated cardiomyopathy in patients of different age[J]. Bull Exp Biol Med, 2018, 164(4):550-553.