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中华妇幼临床医学杂志(电子版) ›› 2024, Vol. 20 ›› Issue (01) : 81 -88. doi: 10.3877/cma.j.issn.1673-5250.2024.01.011

论著

肥胖症儿童血浆脑源性神经营养因子水平及其代谢异常的相关性研究
李英纳1, 李敏1, 周澳洋1, 李平1, 杨凡1,†()   
  1. 1. 四川大学华西第二医院儿科、出生缺陷与相关妇儿疾病教育部重点实验室，成都　610041
  • 收稿日期:2023-11-01 修回日期:2024-01-12 出版日期:2024-02-01
  • 通信作者: 杨凡

Research on plasma brain-derived neurotrophic factor level and its correlation with metabolic abnormalities in obese children

Yingna Li1, Min Li1, Aoyang Zhou1, Ping Li1, Fan Yang1,†()   

  1. 1. Department of Pediatrics, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
  • Received:2023-11-01 Revised:2024-01-12 Published:2024-02-01
  • Corresponding author: Fan Yang
  • Supported by:
    Key Research and Development Program of Science and Technology of Sichuan Province(2023YFS0034); Clinical Development Fund of West China Second University Hospital, Sichuan University(KL119)
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引用本文：

李英纳, 李敏, 周澳洋, 李平, 杨凡. 肥胖症儿童血浆脑源性神经营养因子水平及其代谢异常的相关性研究[J]. 中华妇幼临床医学杂志(电子版), 2024, 20(01): 81-88.

Yingna Li, Min Li, Aoyang Zhou, Ping Li, Fan Yang. Research on plasma brain-derived neurotrophic factor level and its correlation with metabolic abnormalities in obese children[J]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2024, 20(01): 81-88.

目的

探讨肥胖症儿童与体重正常儿童血浆脑源性神经营养因子(BDNF)水平差异，以及其与各代谢表型及代谢指标的关系。

方法

选择2022年3月至10月于四川大学华西第二医院儿科门诊就诊的41例肥胖症儿童为研究对象，纳入肥胖症组。选择同期于本院门诊进行常规体检的11例非肥胖症健康儿童作为对照，纳入对照组。收集2组受试儿体格生长指标及血浆肌肉因子检测结果，包括BDNF、鸢尾素(irisin)、成纤维细胞生长因子(FGF)-21与白细胞介素(IL)-6及-15水平，以及临床检查结果。采用Mann-Whitney U检验，对2组受试儿血浆BDNF水平进行比较。对2组受试儿及脂、糖、嘌呤代谢异常与正常的肥胖症患儿血浆BDNF水平进行差异倍数(FC)分析，若FC>1.20或<0.83，则判断为具有显著FC。采用Spearman秩相关性分析，对2组受试儿人体质量指数(BMI)、BMI标准差评分(BMI-SDS)及血浆IL-6、irisin水平与其血浆BDNF水平进行相关性分析。本研究已获得四川大学华西第二医院医学伦理委员会的批准(审批文号：医学科研2022伦理审批第084号)。2组受试儿年龄、性别构成比、身高等一般临床资料比较，差异均无统计学意义(P>0.05)。

结果

①肥胖症组患儿的体重、BMI，均显著高于对照组(t＝4.30，P<0.001；Z＝－5.05，P<0.001)。②肥胖症组患儿血浆BDNF水平中位数为2 402.0 pg/mL(1 370.0 pg/mL, 3 958.5 pg/mL)，显著高于对照组的1 442.0 pg/mL(933.2 pg/mL, 1 688.0 pg/mL)，差异有统计学意义(Z＝－2.10，P＝0.036)；对2组受试儿血浆BDNF水平进行FC分析结果显示，肥胖症组与对照组受试儿血浆BDNF水平具有显著FC(FC＝1.42)。③脂、糖、嘌呤代谢异常的肥胖症患儿血浆BDNF水平，均分别显著高于脂、糖、嘌呤代谢正常的肥胖症患儿，均具有显著FC(FC＝1.43、1.47、1.98)。④男性受试儿血浆BDNF水平低于女性受试儿，二者血浆BDNF水平具有显著FC(FC＝0.69)。血清25-羟维生素D[25-(OH)-D]重度缺乏、不足受试儿血浆BDNF水平，均高于血清25-(OH)-D正常受试儿，并且均具有显著FC(FC＝1.39、1.51)。血小板计数升高受试儿血浆BDNF水平高于血小板计数正常者，二者血浆BDNF水平具有显著FC(FC＝2.77)。⑤2组受试儿中，其BMI、BMI-SDS及血浆IL-6、Irisin水平与其血浆BDNF水平均呈正相关(rs＝0.396、0.343、0.326、0.656，P＝0.004、0.013、0.018、<0.001)。

结论

BDNF可能参与肥胖症及其相关代谢损伤的发生与发展，并受到性别、血清25-(OH)-D水平、血小板计数及IL-6、irisin等肌肉因子水平等因素的影响。

关键词: 肥胖症，儿童, 脑源性神经营养因子, 肌肉因子, 代谢异常, 脂代谢障碍, 葡萄糖代谢障碍
Objective

To explore the differences in plasma brain-derived neurotrophic factor (BDNF) level between obese and normal children, and its relationship with different metabolic phenotypes and factors.

Methods

A total of 41 obese children who attended the pediatric outpatient clinic of West China Second University Hospital, Sichuan University from March to October 2022 were selected for the study and included in the obese group. Another 11 cases of non-obese healthy children who underwent routine physical examinations in outpatient clinic of our hospital during the control same period were selected as controls and included in the control group. Physical growth indicators, clinical examination results and plasma muscle factors [BDNF, irisin, fibroblast growth factor (FGF)-21 and interleukin (IL)-6 and -15] levels were collected from the 2 groups. Plasma BDNF levels were compared between the 2 groups by Mann-Whitney U test. Plasma BDNF levels were analysed for fold-change (FC) in children between 2 groups and children with abnormal lipid, glucose and purine metabolism versus normal children, and were judged to have a significant FC if FC was >1.20 or <0.83. Correlations of body mass index (BMI), BMI standard deviation scores (BMI-SDS), and plasma levels of IL-6 and irisin with plasma BDNF level in two groups were analyzed by Spearman′s rank correlation test. The study was approved by the Medical Ethics Committee of West China Second University Hospital, Sichuan University (Approval No. 2022-084). The baseline information was not significantly different between the obese and control group (P>0.05), including age, gender ratio, and height.

Results

①The weight and BMI of the obese group were significantly higher than those in the control group (t=4.30, P<0.001; Z=-5.05, P<0.001). ②The median plasma BDNF level of children in obese group was 2 402.0 pg/mL (1 370.0 pg/mL, 3 958.5 pg/mL), which was significantly higher than that of control group 442.0 pg/mL (933.2 pg/mL, 1 688.0 pg/mL), with a statistically significant difference (Z=-2.10, P=0.036); and there was a significant FC between BDNF levels of obese group and control group (FC=1.42). ③Plasma BDNF levels in obese children with abnormal lipid, glucose and purine metabolism were significantly higher than those in obese children with normal lipid, glucose and purine metabolism, with significant FC (FC=1.43, 1.47, 1.98). ④Plasma BDNF level was lower in male than that in female children and had significant FC (FC=0.69). The plasma BDNF levels of children with severe plasma 25-hydroxy vitamin D [25-(OH)-D] deficiency and insufficiency were higher than those of children with normal plasma 25-(OH)-D, and both had significant FC (FC=1.39, 1.51). Children with elevated platelet counts had higher plasma BDNF levels compared to those with normal platelet counts, with a significant FC (FC=2.77). ⑤In 2 groups of children, BMI, BMI-SDS, plasma IL-6 and irisin levels were positively correlated with their plasma BDNF levels (r=0.396, 0.343, 0.326, 0.656; P=0.004, 0.013, 0.018, <0.001).

Conclusions

BDNF may be involved in the occurrence and development of obesity and obesity-related metabolic disorders, and it may be influenced by factors such as gender, serum 25-(OH)-D levels, platelet counts, and levels of muscle factors such as IL-6 and irisin.

Key words: Pediatric obesity, Brain-derived neurotrophic factor, Muscle factor, Metabolic abnormalities, Lipid metabolism disorders, Glucose metabolism disorders
表1 肥胖症组及对照组受试儿相关临床资料比较
组别 例数 性别[例数(%)] 年龄(岁，±s) 身高(cm，±s) 体重(kg，±s) BMI[kg/m2，M(Q1，Q3)]
男 女
肥胖症组 41 10(24.4) 31(75.6) 10.0±2.5 145.0±14.0 55.3±20.4 23.8(22.0，27.5)
对照组 11 6(54.5) 5(45.5) 9.6±2.1 143.5±12.1 43.6±10.0 14.5(14.1，14.8)
统计量   χ2＝3.70 t＝0.51 t＝0.30 t＝4.30 Z＝－5.05
P值   0.054 0.614 0.762 <0.001 <0.001
图1 肥胖症组与对照组受试儿血浆BDNF水平比较(图1A：2组受试儿血浆BDNF水平四分位数箱式图；图1B：2组受试儿血浆BDNF水平中位数及其FC值)注：BDNF为脑源性神经营养因子，FC为差异倍数
表2 各代谢指标异常与正常肥胖症患儿血浆BDNF水平比较及其FC分析
代谢指标结果 异常 正常 FC值 Z值 P值
例数 [pg/mL，M(Q1，Q3)] 例数 [pg/mL，M(Q1，Q3)]
总代谢 12 2 086.0(1 449.0，4 469.3) 29 1 976.5(1 338.5，3 861.0) 1.06 －0.49 0.641
脂代谢 17 2 462.0(1 720.0，4 252.5) 24 1 713.5(1 260.2，3 289.2) 1.43a －1.35 0.177
HDL-C 2 3 152.0(2 619.0，3 685.0) 37 1 820.0(1 338.5，3 601.5) 1.73a －0.83 0.456
LDL-C 4 2 805.5(1 097.1，4 269.8) 35 1 911.0(1 347.0，3 504.0) 1.46a －0.05 0.982
TG 6 2 274.0(1 682.9，3 828.8) 33 1 765.0(1 338.5，3 895.5) 1.29a －0.51 0.635
脂肪肝 8 3 413.5(1 352.0，11 563.3) 33 1 911.0(1 370.0，3 141.0) 1.79a －1.35 0.186
糖代谢 21 2 462.0(1 658.5，4506.5) 20 1 677.0(1 200.3，2 566.5) 1.47a －1.69 0.090
2 h PBG 2 2 659.5(2 139.8，3 179.3) 36 2 064.0(1 403.8，4 039.5) 1.29a －0.13 0.922
HOMA-IR 12 1 976.5(1 449.8，4 469.3) 29 2 086.0(1 338.5，3 861.0) 0.94 －0.49 0.641
嘌呤代谢 7 3 699.0(1 697.0，4 726.0) 34 1 865.5(1 306.8，2 959.5) 1.98a －1.66 0.101
图2 不同性别、血清25-(OH)-D缺乏程度受试儿血浆BDNF水平差异分析(图2A：不同性别受试儿血浆BDNF水平中位数和FC值；图2B：不同血清25-(OH)-D水平受试儿血浆BDNF水平中位数和FC值)注：①、②、③分别指血清25-(OH)-D重度缺乏[血清25-(OH)-D水平<20 pg/mL]、不足[血清25-(OH)-D水平≥20～30 pg/mL]、正常[血清25-(OH)-D水平≥30 pg/mL]受试儿。25-(OH)-D为25-羟维生素D，BDNF为脑源性神经营养因子，FC为差异倍数
表3 不同性别、血清25-(OH)-D水平、血小板计数受试儿血浆BDNF水平比较及其FC分析
临床指标 例数 血浆BDNF水平[pg/ml，M(Q1，Q3)] FC值 统计量 P值
性别     0.69c Z＝－0.31 0.754
男 37 1 730.0(1 283.5，2 953.0)      
女 15 2 086.0(1 157.0，4 993.0)      
血清25-(OH)-D a     —d H＝1.52 0.468
重度缺乏 13 1 911.0(1 197.0，3 601.5)      
不足 22 2 143.5(1 678.8，4 235.0)      
正常 6 1 383.0(1 023.9，6 478.5)      
血小板计数b     2.77c Z＝－1.71 0.090
升高 4 3 861.0(2 309.3，13 097.3)      
正常 28 1 792.5(1 334.3，3 556.3)      
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