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北京大学学报（医学版） ›› 2024, Vol. 56 ›› Issue (4): 722-728. doi: 10.19723/j.issn.1671-167X.2024.04.028

• 论著 • 上一篇    下一篇

血浆中脂质代谢分子与颈动脉粥样硬化斑块、传统心血管危险因素及膳食因素的关系

和静1,2,房中则3,杨颖4,刘静5,马文瑶2,霍勇4,高炜6,武阳丰1,2,7,8,谢高强1,2,7,8,*()   

  1. 1. 北京大学第一医院, 北京 100034
    2. 北京大学临床医学高等研究院临床研究所, 北京 100191
    3. 天津医科大学公共卫生学院, 天津 300070
    4. 北京大学第一医院心内科, 北京 100034
    5. 首都医科大学附属北京安贞医院临床与流行病研究中心, 北京 100029
    6. 北京大学第三医院心内科, 北京 100191
    7. 重大疾病流行病学教育部重点实验室(北京大学), 北京 100191
    8. 血管稳态与重构全国重点实验室(北京大学), 北京 100191
  • 收稿日期:2021-06-11 出版日期:2024-08-18 发布日期:2024-07-23
  • 通讯作者: 谢高强 E-mail:gxie@bjmu.edu.cn
  • 基金资助:
    国家自然科学基金(30872168);国家自然科学基金(81473044)

Relationship between lipid metabolism molecules in plasma and carotid atheroscle-rotic plaques, traditional cardiovascular risk factors, and dietary factors

Jing HE1,2,Zhongze FANG3,Ying YANG4,Jing LIU5,Wenyao MA2,Yong HUO4,Wei GAO6,Yangfeng WU1,2,7,8,Gaoqiang XIE1,2,7,8,*()   

  1. 1. Peking University First Hospital, Beijing 100034, China
    2. Clinical Research Institute, Institute of Advanced Clinical Medicine, Peking University, Beijing 100191, China
    3. College of Public Health, Tianjin Medical University, Tianjin 300070, China
    4. Department of Cardiology, Peking University First Hospital, Beijing 100034, China
    5. Center of Clinical and Epidemiology, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China
    6. Department of Cardiology, Peking University Third Hospital, Beijing 100191, China
    7. Key Laboratory of Epidemiology of Major Diseases (Peking University), Beijing 100191, China
    8. State Key Laboratory of Vascular Homeostasis and Remodeling (Peking University), Beijing 100191, China
  • Received:2021-06-11 Online:2024-08-18 Published:2024-07-23
  • Contact: Gaoqiang XIE E-mail:gxie@bjmu.edu.cn
  • Supported by:
    the National Natural Science Foundation of China(30872168);the National Natural Science Foundation of China(81473044)

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摘要：

目的: 探索血浆中脂质代谢分子与颈动脉粥样硬化斑块、传统心血管危险因素的关系及可能的膳食相关因素。方法: 从参加2012年“亚临床动脉粥样硬化队列10年随访研究”的北京市石景山区1 312名社区人群中，按照入排标准(年龄 < 70岁、无临床心血管病及其他疾病等)筛选出85名有2个以上颈动脉软斑块或混合斑块者，以及相匹配的89名无斑块对照者；然后从中各随机抽取10名分别作为病例组和对照组。颈动脉斑块采用GE Vivid i超声仪(8L探头)确定。采用高效液相色谱-质谱联用法对脂质代谢分子进行检测，检测指标包括113种脂质代谢分子。传统心血管危险因素使用统一的标准问卷进行采集，膳食相关因素采用膳食使用频率和重量问卷进行采集。采用Wilcoxin秩和检验分析病例组和对照组脂质代谢分子的差异，在对照组中，采用Spearman相关法描述有统计学意义的脂质代谢分子与传统心血管危险因素、膳食因素的相关关系。结果: 在113种脂质代谢分子中检测出的53种脂质分子中，C24：0鞘磷脂，C22：0、C24：0神经酰胺，C18：0磷脂酰乙醇胺，C18：2 (Cis) 磷脂酰胆碱，C18：0磷脂酰胆碱等在颈动脉粥样硬化斑块病例组显著高于无斑块对照组。对照组相关分析发现，C24：0鞘磷脂与低密度脂蛋白胆固醇呈显著正相关(r=0.636，P < 0.05)，C18：2 (Cis) 磷脂酰胆碱与收缩压呈显著正相关(r=0.733，P < 0.05)，C18：0磷脂酰乙醇胺与高敏C反应蛋白呈显著正相关(r=0.782，P < 0.01)，C22：0、C24：0神经酰胺及C18：0磷脂酰乙醇胺与蔬菜摄入量呈显著负相关(r=-0.679，P < 0.05；r=-0.711，P < 0.05；r=-0.808，P < 0.01)，C24：0神经酰胺与豆类食品摄入量呈显著负相关(r=-0.736，P < 0.05)。结论: 血浆C24：0鞘磷脂、C22：0和C24：0神经酰胺、C18：0磷脂酰乙醇胺、C18：2和C18：0磷脂酰胆碱等脂质代谢分子升高可能是人类动脉粥样硬化斑块的新危险因素，这些分子可能与血脂、血压或炎症水平及蔬菜、豆制品摄入有关，但关联的性质需要在更大样本人群中验证。

关键词: 脂质代谢分子, 动脉粥样硬化, 相关分析, 危险因素

Abstract:

Objective: To explore the relationship between lipid metabolism molecules in plasma and carotid atherosclerotic plaques, traditional cardiovascular risk factors and possible dietary related factors. Methods: Firstly, among 1 312 community people from those who participated in a 10-year follow-up study of subclinical atherosclerosis cohort in Shijingshan District, Beijing, 85 individuals with 2 or more carotid soft plaques or mixed plaques and 89 healthy individuals without plaques were selected according to the inclusive and the exclusive criteria (< 70 years, not having clinical cardiovascular disease and other diseases, etc.). Secondly, 10 cases and 10 controls were randomly selected in the above 85 and 89 individuals respectively. Carotid plaques were detected using GE Vivid i Ultrasound Machine with 8L detector. Lipid metabolism molecules were detected by high performance liquid chromatography-mass spectrometry. The detection indexes included 113 lipid metabolism molecules. Traditional cardiovascular risk factors were collected by unified standard questionnaires, and dietary related factors were collected by main dietary frequency and weight scale. The difference of lipid metabolism molecules between the case group and the control group was analyzed by Wilcoxin rank test. In the control group, the Spearman correlation method was used to analyze the correlation between statistically significant lipid metabolism molecules and traditional cardiovascular risk factors and dietary factors. Results: Among the 113 lipid metabolism molecules, 53 lipid metabolism molecules were detected. C24:0 sphingomyelin (SM), C22:0/ C24:0 ceramide molecules, C18:0 phosphoethanolamine (PE) molecules, and C18:0/C18:2 (Cis) phosphatidylcholine (PC) were significantly higher in the carotid atherosclerotic plaque group than in the control group. The correlation analysis showed that C24:0 SM was significantly positively correlated with low density lipoprotein cholesterol (LDL-C, r=0.636, P < 0.05), C18:2 (Cis) PC (DLPC) was significantly positively correlated with systolic pressure (r=0.733, P < 0.05), C18:0 PE was significantly positively correlated with high sensitivity C-response protein (r=0.782, P < 0.01), C22:0, C24:0 ceramide and C18:0 PE were negatively correlated with vegetable intake (r=-0.679, P < 0.05;r=-0.711, P < 0.05;r=-0.808, P < 0.01), C24:0 ceramide was also negatively correlated with beans food intake (r=-0.736, P < 0.05) in the control group. Conclusions: The increase of plasma C24:0 SM, C22:0, C24:0 ceramide, C18:0 PE, C18:2 (Cis) PC (DLPC), C18:0 PC (DSPC) may be new risk factors for human atherosclerotic plaques. These molecules may be related to blood lipid, blood pressure or inflammatory level and the intake of vegetables and soy products, but the nature of the association needs to be verified in a larger sample population.

Key words: Lipid metabolism molecules, Atherosclerosis, Correlation analysis, Risk factors

中图分类号: 

  • R543.4

表1

动脉粥样硬化斑块组和对照组病例的人口统计学指标比较"

Variables Atherosclerotic plaque group (n=10) Control group (n=10) P value
Age/years 61.68 (58.42－67.04) 62.97 (55.92－68.62) 0.734
Male 6 (60) 5 (50) 1.000
Smoking 2 (20) 2 (20) 1.000
BMI/(kg/m2) 24.80 (19.75－28.89) 26.11 (18.00－29.59) 0.473
SBP/mmHg 139.50 (111.67－184.67) 123.67 (110.33－149.00) 0.140
DBP/mmHg 78.50 (71.67－119.00) 72.00 (67.00－97.67) 0.162
Glucose/(mmol/L) 5.64 (4.38－6.79) 5.24 (4.89－9.43) 0.623
LDL-C/(mmol/L) 4.21 (2.08－6.00) 3.05 (1.26－4.57) 0.054
hs-CRP/(mg/L) 2.37 (0.57－6.75) 1.51 (0.61－7.39) 0.473
History of CVD
Hypertension 7 (70) 4 (40) 0.370
Diabetes 2 (20) 3 (30) >0.999
Angina/MI 0 0 -
Stroke 0 0 -
Treatment
Antihypertensive 3 (30) 3 (30) 1.0
Lipid lowering 0 (0) 0 (0) -
Insulin 0 3 (30) 0.211
Oral hypoglycemic drugs 2 (20) 1 (10) >0.999
Aspirin 3 (30) 1 (10) 0.582

图1

脂质分子检测的峰面积"

表2

动脉粥样硬化斑块组与对照组脂质代谢分子检测结果"

Items Lipidomics indications Total(n=20) Control group (n=10) Atherosclerotic plaque group (n=10) P value
Ceramide C24:0 ceramide 1.39 (0.75－3.03) 1.25 (0.75－2.14) 1.63 (1.27－3.03) 0.009
C22:0 ceramide 0.45 (0.21－1.02) 0.42 (0.21－0.57) 0.52 (0.43－1.02) 0.011
C24:1 ceramide 0.62 (0.27－1.32) 0.49 (0.27－0.70) 0.69 (0.41－1.32) 0.054
C20:0 ceramide 0.09 (0.04－0.20) 0.08 (0.04－0.12) 0.10 (0.05－0.20) 0.076
Phosphatidylcholine (PC) C18:2 (Cis) PC 8.94 (3.90－15.85) 7.31 (3.90－15.70) 10.71 (8.27－15.85) 0.021
C18:0 PC 0.14 (0.06－0.25) 0.12 (0.06－0.21) 0.16 (0.11－0.25) 0.045
C16:1 (Δ9-Cis) PC 1.27 (0.53－2.05) 1.09 (0.53－2.05) 1.62 (0.87－1.93) 0.076
C18:0-22:6 PC 6.76 (3.71－15.14) 5.34 (3.71－15.14) 7.73 (5.71－11.07) 0.162
C20:4 (Cis) PC 0.22 (0.06－0.45) 0.20 (0.06－0.45) 0.24 (0.12－0.39) 0.186
Phosphorylethanolamine (PE) C18:0 PE 0.02 (0.01－0.12) 0.01 (0.01－0.03) 0.02 (0.01－0.12) 0.045
C18:0-C18:1 PE 0.37 (0.14－1.35) 0.27 (0.14－0.50) 0.40 (0.19－1.35) 0.121
C18:0-C18:2 PE 1.90 (0.79－4.14) 1.66 (0.79－4.14) 1.99 (1.15－3.17) 0.121
Sphingomyelin (SM) C24:0 SM 12.19 (6.62－16.09) 10.65 (6.62－15.24) 13.35 (10.44－16.09) 0.017

表3

健康对照组脂质分子与心血管危险因素、膳食因素的Spearman相关系数"

Cardiovascular risk factors C22:0 ceramide C24:0 ceramide C18:2 (Cis) PC (DLPC) C18:0 PC (DSPC) C18:0 PE C24:0 SM
LDL-C 0.188 0.079 －0.091 0.030 －0.115 0.636*
Smoking count 0.147 －0.009 －0.277 －0.398 －0.138 0.389
BMI 0.055 －0.006 －0.370 －0.115 0.479 －0.006
SBP 0.576 0.430 0.733* 0.139 0.261 0.042
DBP 0.430 0.236 0.164 0.200 －0.042 0.188
Fasting blood sugar 0.030 0.103 0.006 －0.292 －0.213 －0.389
hs-CRP 0.297 0.200 0.115 0.345 0.782** －0.406
Dietary
Staple food －0.617 －0.541 0.171 －0.021 －0.350 0.212
Bean products －0.334 －0.736* －0.057 0.334 －0.145 －0.094
Chicken and duck －0.069 －0.130 －0.034 0.021 －0.370 0.384
Beef, pork, and lamb 0.113 0.094 －0.044 －0.183 －0.378 0.390
Fish －0.268 －0.268 0.482 0.389 －0.322 0.409
Eggs －0.228 －0.319 0.156 0.410 －0.189 －0.286
Milk and dairy products －0.308 0.130 －0.260 －0.082 －0.185 0.226
Vegetables －0.679* －0.711* －0.162 －0.129 －0.808** 0.323
Fruit －0.020 0.203 －0.334 0.400 0.374 0.361
Nut －0.256 －0.479 －0.479 0.177 －0.059 0.007
Pickle 0.000 0.000 －0.355 －0.355 0.355 －0.284
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ISSN 1671-167X
CN 11-4691/R
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