[1]刘恒道,吕风华,郭令利,等.二肽基肽酶4在糖尿病患者并发冠状动脉粥样硬化性心脏病中的作用及其机制[J].新乡医学院学报,2021,38(6):520-525.[doi:10.7683/xxyxyxb.2021.06.005]
　LIU Hengdao,LYU Fenghua,GUO Lingli,et al.Role and mechanism of dipeptidyl peptidase 4 in diabetes mellitus combined with coronary atherosclerotic heart disease[J].Journal of Xinxiang Medical University,2021,38(6):520-525.[doi:10.7683/xxyxyxb.2021.06.005]
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二肽基肽酶4在糖尿病患者并发冠状动脉粥样硬化性心脏病中的作用及其机制
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《新乡医学院学报》[ISSN:1004-7239/CN:41-1186/R]

卷:
38
期数:
2021年6
页码:
520-525
栏目:
临床研究
出版日期:
2021-06-05

文章信息/Info

Title:
Role and mechanism of dipeptidyl peptidase 4 in diabetes mellitus combined with coronary atherosclerotic heart disease
作者:
刘恒道1; 吕风华2; 郭令利3; 刘宇宙1; 朱瑞芳1; 白雪洋1; 朱　鑫1; 孙云龙1; 石　琳3; 孟　哲1
（1.郑州大学第一附属医院心血管内科，河南　郑州　450052；2.新乡医学院第一附属医院心血管内一科，河南　卫辉453100；3.河南省直第三人民医院内分泌科，河南　郑州　450006）
Author(s):
LIU Hengdao1; LYU Fenghua2; GUO Lingli3; LIU Yuzhou1; ZHU Ruifang1; BAI Xueyang1; ZHU Xin1; SUN Yunlong1; SHI Lin3; MENG Zhe1
(1.Department of Cardiology,the First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,Henan Province,China2.Department of Cardiology,the First Affiliated Hospital of Xinxiang Medical University,Weihui 453100,Henan Province,China3.Department of Endocrinology,the Third People′s Provincial Hospital of Henan Province,Zhengzhou 450006,Henan Province,China)
关键词:
糖尿病; 冠状动脉粥样硬化性心脏病; 二肽基肽酶4; 内皮细胞功能障碍
Keywords:
diabetes mellituscoronary atherosclerotic heart diseasedipeptidyl peptidase 4endothelial dysfunction
分类号:
R543.3
DOI:
10.7683/xxyxyxb.2021.06.005
文献标志码:
A
摘要:
目的　探讨糖尿病（DM）并发冠状动脉粥样硬化性心脏病（CAHD）患者血清二肽基肽酶4（DPP4）水平的变化及其对血管损伤的机制。方法　选择2018年9月至2019年9月郑州大学第一附属医院心血管内科收治的疑诊DM或（和）CAHD患者164例，根据病史和冠状动脉造影结果将患者分为对照组（n=42）、DM组（n=41）、CAHD组（n=43）、DM+CAHD组（n=38）；测量各组患者入院时收缩压（SBP）、舒张压（DBP），应用全自动生物化学分析仪检测各组患者空腹血糖（FBG）、餐后2小时血糖（2 h-PBG）、低密度脂蛋白（LDL）、高密度脂蛋白（HDL）、总胆固醇（TC）、三酰甘油（TG）水平，酶联免疫吸附法测定各组患者血清DPP4和晚期糖基化终末产物（AGEs）水平。取对数生长期人脐静脉内皮细胞（HUVECs）随机分为对照组、100 μg·L-1DPP4干预组、500 μg·L-1DPP4干预组，分别给予无血清达尔伯克改良伊格尔培养基、100 μg·L-1 DPP4、500 μg·L-1 DPP4干预24 h，应用硝酸还原酶法检测HUVECs上清液中一氧化氮（NO）水平，Western blot检测HUVECs中内皮型一氧化氮合酶Ser1177位点（PeNOSSer1177）磷酸化水平。结果　DM组患者SBP、FBG、2 h-PBG、TC水平高于对照组（P＜0.05），CAHD组患者SBP、LDL、TC水平高于对照组（P＜0.05），DM+CAHD组患者SBP、FBG、2 h-PBG、LDL、TC、TG水平高于对照组（P＜0.05）；CAHD组患者SBP水平高于DM组，2 h-PBG水平低于DM组（P＜0.05）；DM+CAHD组患者FBG、2 h-PBG、TG水平高于DM组和CAHD组（P＜0.05）。DM组、CAHD组、DM+CAHD组患者血清DPP4、AGEs水平高于对照组（P＜0.05）， DM+CAHD组患者血清DPP4、AGEs高于DM组和CAHD组（P＜0.05），DM组与CAHD组患者血清DPP4、AGEs水平比较差异均无统计学意义（P＞0.05）。4组患者血清DPP4水平与AGEs水平均呈正相关（P＜0.05）。对照组患者血清DPP4水平与LDL、HDL、TC、TG、FBG、2 h-PBG、SBP、DBP无相关性（P＞0.05）；DM组、CAHD组及DM+CAHD组患者血清DPP4水平与LDL、TC、 FBG、2 h-PBG、SBP水平呈正相关（P＜0.05）。100 μg·L-1DPP4干预组和500 μg·L-1DPP4干预组HUVECs上清液中NO水平和 peNOSSer1177相对表达量显著低于对照组（P＜0.05），500 μg·L-1DPP4干预组HUVECs上清液中NO水平和peNOSSer1177相对表达量显著低于100 μg·L-1DPP4干预组（P＜0.05）。结论　DPP4可导致内皮细胞功能失常，造成血管损伤，参与DM患者CAHD的发生、发展。
Abstract:
Objective　To investigate the changes of serum dipeptidyl peptidase 4 (DPP4) level of patients with diabetes mellitus (DM) combined with coronary atherosclerotic heart disease (CAHD) and its effect on vascular injury.Methods　　One hundred and sixty-four patients with suspected DM or (and) CAHD admitted to Department of Cardiology,the First Affiliated Hospital of Zhengzhou University from September 2018 to September 2019 were selected as study subjects.All subjects were divided into control group (n=42),DM group (n=41),CAHD group (n=43) and DM+CAHD group (n=38) according to medical history and coronary angiography results.Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measared at admission,and the levels of fasting blood glucose (FBG),2-hours postprandial blood glucose (2 h-PBG),low-density lipoprotein (LDL),high-density lipoprotein (HDL),total cholesterol (TC) and triglyceride (TG) were measured by fully automated biochemistry analyzer.Serum DPP4 and advanced glycosylation end products (AGEs) levels were measured by enzyme linked immunosorbent assay.The human umbilical vein endothelial cells(HUVECs) in logarithmic phase were collected and randomly divided into control group,100 μg·L-1 DPP4 treatment group and 500 μg·L-1 DPP4 treatment group,and the cells were treated with serum-free Dulbecco′s modified Eagle′s medium,100 μg·L-1 DPP4 and 500 μg·L-1 DPP4 for 24 hours,respectively.The level of nitric oxide (NO) in supernatant of HUVECs was detected by nitrate reductase assay and the relative expression of phosphorylation of endothelial nitric oxide synthase(eNOS) at Ser1177（peNOSSer1177）in HUVECs were detected by Western blot.Results　The levels of SBP,FBG,2 h-PBG and TC of patients in the DM group were significantly higher than those in the control group (P<0.05);the levels of SBP,LDL and TC of patients in the CAHD group were significantly higher than those in the control group (P<0.05);the levels of SBP,FBG,2 h-PBG,LDL,TC and TG of patients in the DM + CAHD group were significantly higher than those in the control group (P<0.05);the level of SBP of patients in the CAHD group was significantly higher than that in the DM group (P<0.05),the level of 2 h-PBG of patients in the CAHD group was significantly lower than that in the DM group (P<0.05);the levels of FBG,2 h-PBG and TG of patients in the DM + CAHD group were significantly higher than those in the DM group and CAHD group (P<0.05).The levels of serum DPP4 and AGEs of patients in the DM group,CAHD group and DM+CAHD group were significantly higher than those in the control group (P<0.05),the levels of serum DPP4 and AGEs of patients in the DM+CAHD group were significantly higher than those in the DM group and CAHD group (P<0.05),there was no significant difference in the levels of serum DPP4 and AGEs of patients between the DM group and CAHD group (P>0.05).The level of serum DPP4 was positively correlated with AGEs in the four groups (P<0.05).The level of serum DPP4 of patients in the control group was not correlated with LDL,HDL,TC,TG,FBG,2h-PBG,SBP,DBP(P>0.05);the level of serum DPP4 was positively correlated with the levels of LDL,TC,FBG,2 h-PBG and SBP of patients in the DM group,CAHD group and DM+CAHD group(P<0.05).The level of NO and relative expression of peNOSSer1177 in HUVECs in the 100 μg·L-1 DPP4 treatment group and 500 μg·L-1 DPP4 treatment group were significantly lower than those in the control group(P<0.05),the level of NO and relative expression of peNOSSer1177in HUVECs in the 500 μg·L-1 DPP4 treatment group were significantly lower than those in the 100 μg·L-1 DPP4 treatment group (P<0.05).Conclusion　DPP4 can cause vascular injury by inducing the endothelial dysfunction,which participates in the occurrence and development of DM combined with CAHD.

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更新日期/Last Update: 2021-06-05