双相情感障碍患者外周血中FGF1的表达与糖脂代谢的相关性

doi:10.3969/j.issn.1004-583X.2025.07.006

摘要/Abstract

摘要：

目的研究稳定期双向情感障碍患者(Bipolar disorder, BD)血清中成纤维细胞生长因子1(fibroblast growth factor 1, FGF1)的表达水平以及与糖脂代谢的相关性。方法选取2024年3月-2024年12月在社区卫生服务中心管理下的110例稳定期双向情感障碍患者为研究对象,其中分52例服药组(Bipolar disorder medication group, BD-M),58例未服药组(Bipolar disorder no medication group, BD-NM),另选取同期60例健康体检人群为对照组。检测并比较各组血清FGF1水平及糖脂代谢相关指标水平,分析FGF1与糖脂代谢相关性。结果 BD-NM组和BD-M组的血糖高于对照组(P值均<0.05),而高密度脂蛋白胆固醇低于对照组(P值均<0.05);与健康组相比,BD-M组的甘油三酯、胆固醇、低密度脂蛋白胆固醇、载脂蛋白A、载脂蛋白B、脂蛋白a显著增高(P值均<0.05),而总蛋白降低(P<0.01)。BD-M组的甘油三酯、胆固醇、载脂蛋白A、载脂蛋白B、脂蛋白a比BD-NM组高(P值均<0.05),BD-M组的总蛋白低于BD-NM组(P<0.05)。血清FGF1水平,BD-M组>BD-NM组>对照组(P<0.05)。Spearman相关分析发现BD-M组的血清FGF1水平与血糖、甘油三酯、胆固醇、低密度脂蛋白胆固醇、载脂蛋白B呈正相关(P值均<0.05),与总蛋白呈负相关(P<0.05)。结论服药的双向情感患者血清中高水平的 FGF1 表达与药物所致的糖脂代谢紊乱具有相关性,FGF1可能用于监测或预防精神药物引起的代谢异常。

关键词: 双向情感障碍, 成纤维细胞生长因子1, 外周血, 糖脂代谢参数, 药物治疗

Abstract:

Objective To study serum level of fibroblast growth factor 1 (FGF1) and the correlation with glucose and lipid metabolism in patients with stable bipolar disorder (BD). Methods A total of 110 patients with stable BD under the management of community health service centers from March 2024 to December 2024 were selected as the study objects, involving 52 patients in the bipolar disorder medication group (BD-M), and 58 in the bipolar disorder no medication group (BD-NM). During the same period, 60 healthy volunteers receiving physical examinations were selected as the control group. Serum FGF1 level and glucose and lipid metabolism were measured and compared. The correlation of FGF1 with glucose and lipid metabolism was analyzed. Results Blood glucose was significantly higher in the BD-NM group and BD-M group than the control group, while the high-density lipoprotein cholesterol (HDL-C) was significantly lower (all P<0.05). Compared to the control group, triglycerides (TG), cholesterol (CHOL), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A (ApoA), apolipoprotein B (ApoB) and lipoprotein a (LPa) were significantly higher in the BD-M group (all P<0.05), while the total protein (TP) was significantly lower (P<0.01). TG, CHOL, ApoA, ApoB and LPa in the BD-M group were significantly higher than the BD-NM group (all P<0.05), while TP was significantly lower (P<0.05). The highest serum FGF1 was found in the BD-M group, followed by BD-NM group and control group (P<0.05). Spearman Correlation analysis showed that serum FGF1 levels in the BD-M group were positively correlated with blood glucose, TG, CHOL, LDL-C and ApoB (all P<0.05), but negatively correlated with TP (P<0.05). Conclusion Increase serum FGF1 in BD patients is correlated with medication-induced glucose and lipid metabolism disorders, and FGF1 may be used to monitor or prevent metabolic abnormalities induced by psychotropic drugs.

Key words: bipolar disorder, fibroblast growth factor 1, peripheral blood, glucose and lipid metabolism parameters, psychotropic medication treatment

中图分类号:

R749.4

卢远思, 吕见君, 官计彬, 操龙斌. 双相情感障碍患者外周血中FGF1的表达与糖脂代谢的相关性[J]. 临床荟萃, 2025, 40(7): 619-623.

Lu Yuansi, Lv Jianjun, Guan Jibin, Cao Longbin. Correlation of serum FGF1 expression with glucose and lipid metabolism in bipolar disorder[J]. Clinical Focus, 2025, 40(7): 619-623.

导出引用管理器 EndNote|Ris|BibTeX

链接本文: http://www.lchc.cn/CN/10.3969/j.issn.1004-583X.2025.07.006

http://www.lchc.cn/CN/Y2025/V40/I7/619

图/表 4

参考文献 22

[1]	Carvalho AF, Firth J, Vieta E. Bipolar Disorder[J]. N Engl J Med, 2020, 383(1):58-66.
[2]	Nierenberg AA, Agustini B, Köhler-Forsberg O, et al. Diagnosis and treatment of bipolar disorder: A review[J]. JAMA, 2023, 330(14):1370-1380. doi: 10.1001/jama.2023.18588 pmid: 37815563
[3]	IsHak WW, Brown K, Aye SS, et al. Health-related quality oflife in bipolar disorder[J]. Bipolar Disord, 2012, 14(1):6-18.
[4]	Yatham LN, Kennedy SH, Parikh SV, et al. Canadian Networkfor Mood and Anxiety Treatments(CANMAT) and InternationalSociety for Bipolar Disorders (ISBD) 2018 guidelines for themanagement of patients with bipolar disorder[J]. Bipolar Disord, 2018, 20(2):97-170.
[5]	Galvez-Contreras AY, Campos-Ordonez T, Lopez-Virgen V, et al. Growth factors as clinical biomarkers of prognosis and diagnosis in psychiatric disorders[J]. Cytokine Growth Factor Rev, 2016,32:85-96.
[6]	Greenhill C. FGF1 signalling cascade suppresses lipolysis[J]. Nat Rev Endocrinol, 2022, 18(3):135.
[7]	姬卫秀, 李萌, 赵云罡. 基于成纤维细胞生长因子1的药物治疗肥胖相关并发症[J]. 生物化学与生物物理进展, 2024, 51(6):1341-1356.
[8]	张明园, 何燕玲. 精神科评定量表手册[M]. 长沙: 湖南科学技术出版社, 2015: 128-328.
[9]	Rush AJ, Bernstein IH, Trivedi MH, et al. An evaluation of the quick inventory of depressive symptomatology and the hamilton rating scale for depression: A sequenced treatment alternatives to relieve depression trial report[J]. Biol Psychiatry, 2006, 59(6):493-501.
[10]	Nielsen RE, Banner J, Jensen SE. Cardiovascular disease in patients with severe mental illness[J]. Nat Rev Cardiol, 2021, 18(2):136-145. doi: 10.1038/s41569-020-00463-7 pmid: 33128044
[11]	Goldfarb M, De Hert M, Detraux J, et al. Severe mental illness and cardiovascular disease: JACC state-of-the-art review[J]. J Am Coll Cardiol, 2022, 80(9):918-933. doi: 10.1016/j.jacc.2022.06.017 pmid: 36007991
[12]	沈阿姿, 孙静. 双相障碍共病躯体疾病的研究进展[J]. 中华精神科杂志, 2020, 53(6):537-541.
[13]	崔东红. 双相障碍的代谢障碍及相关发病机制[J]. 中华精神科杂志, 2022, 55(3) :175-181.
[14]	Kalelioglu T, Genc A, Karamustafalioglu N, et al. Assessment of cardiovascular risk via atherogenic indices in patients with bipolar disorder manic episode and alterations with treatment[J]. Diabetes Metab Syndr, 2017, 11(Suppl 1):S473-S475.
[15]	Nihalani N, Schwartz TL, Siddiqui UA, et al. Obesity and psychotropics CNS neurosci[J]. Ther, 2020, 8(1):57-63.
[16]	Luo H, Jiang ZL, Ren Y. Therapy management of metabolic disorder comorbidity with depression[J]. Front Psychol, 2021,12:683320.
[17]	Suh JM, Jonker JW, Ahmadian M, et al. Endocrinization of FGF1 produces a neomorphic and potent insulin sensitizer[J]. Nature, 2014, 513(7518):436-439.
[18]	Sancar G, Liu S, Gasser E, et al. FGF1 and insulin control lipolysis by convergent pathways[J]. Cell Metab, 2022, 34(1):171-183.e6. doi: 10.1016/j.cmet.2021.12.004 pmid: 34986332
[19]	Wang J, Zhang F, Yang W, et al. FGF1 ameliorates obesity-associated hepatic steatosis by reversing IGFBP2 hypermethylation[J]. FASEB J, 2023, 37(4):e22881.
[20]	Perry RJ, Lee S, Ma L, et al. FGF1 and FGF19 reverse diabetes by suppression of the hypothalamic-pituitary-adrenal axis[J]. Nat Commun, 2015, 6:6980. doi: 10.1038/ncomms7980 pmid: 25916467
[21]	Zhao Y, Ye S, Lin J, et al. Corrigendum: NmFGF1-regulated glucolipid metabolism and angiogenesis improves functional recovery in a mouse model of diabetic stroke and acts via the AMPK signaling pathway[J]. Front Pharmacol, 2024, 15:1392148.
[22]	Kao CY, Hsu YC, Liu JW, et al. The mood stabilizer valproate activates human FGF1 gene promoter through inhibiting HDAC and GSK-3 activities[J]. J Neurochem, 2013, 126(1):4-18.

项目	HC(n=60)	BD-NM(n=58)	BD-M(n=52)	F/χ²/Z值	P值
年龄(岁)	38(35,45)	39(35,47)	39(35,47)	0.810	0.447
男/女[例(%)]	28(47.0)/32(53.0)	27(46.5)/31(52.5)	29(55.8)/23(44.2)	1.210	0.546
BMI	22.61±3.04	23.79±3.83	23.81±3.70	2.232	0.111
SBP(mmHg)	123.9±19.27	131.86±15.01	129.21±15.29	1.135	0.324
DBP(mmHg)	78.33±1.28	77.75±8.34	79.52±5.36	3.845	0.069

项目	HC(n=60)	BD-NM(n=58)	BD-M(n=52)	F/χ²/Z值	P值
年龄(岁)	38(35,45)	39(35,47)	39(35,47)	0.810	0.447
男/女[例(%)]	28(47.0)/32(53.0)	27(46.5)/31(52.5)	29(55.8)/23(44.2)	1.210	0.546
BMI	22.61±3.04	23.79±3.83	23.81±3.70	2.232	0.111
SBP(mmHg)	123.9±19.27	131.86±15.01	129.21±15.29	1.135	0.324
DBP(mmHg)	78.33±1.28	77.75±8.34	79.52±5.36	3.845	0.069

项目	HC(n=60)	BD-NM(n=58)	BD-M(n=52)	F/Z值	P值
GLU(mmol/L)	4.82(4.50,5.18)	5.45(4.97,6.33)^△	5.81(4.55,6.58)^△	12.59	<0.01
TG(mmol/L)	1.13(0.90,1.62)	1.42(0.97,2.32)	2.33(1.70,3.26)^△▲	25.17	<0.01
CHOL(mmol/L)	5.31(4.74,6.28)	5.26(4.40,6.00)	6.47(5.29,7.71)^△▲	13.18	<0.01
HDL-C(mmol/L)	1.54±0.32	1.36±0.34^△	1.32±0.88^△	8.79	<0.01
LDL-C(mmol/L)	3.08±0.79	3.34±0.88	3.48±0.95^*	3.07	0.039
APO-A(g/L)	1.41(1.33,1.49)	1.35(1.32,1.51)	1.89(1.79,1.98)^△▲	115.30	<0.01
APO-B(g/L)	1.07(1.03,1.11)	1.04(0.84,1.11)	1.37(1.17,1.64)^△▲	34.67	<0.01
LPa(mg/dl)	7.60(5.27,9.32)	8.70(4.00,16.15)	10.2(8.25,11.95)^△#	15.25	<0.01
TP(g/L)	69.06±12.13	65.82±8.47	61.38±5.85^△#	9.48	<0.01
ALB(g/L)	36.20±5.29	37.47±7.39	33.63±6.07	2.23	0.106
ALT(U/L)	16.50(13.00,22.75)	17.00(12.59,23.68)	17.21(9.87,24.21)	0.10	0.905
AST(U/L)	23.00(20.25,27.01)	23.12(20.00,27.25)	22.36(20.21,29.36)	0.28	0.758
CR(μmol/L)	67.65(57.67,79.87)	72.90(57.52,91.47)	74.8(66.47,83.95)	2.16	0.118
UREA(mmol/L)	5.66(4.59,6.46)	5.79(4.63,6.89)	5.73(4.81,6.94)	0.10	0.902
UA(μmol/L)	323.01(294.24,401.14)	359.82(286.25,426.75)	358.48(270.25,414.51)	2.70	0.069

项目	HC(n=60)	BD-NM(n=58)	BD-M(n=52)	F/Z值	P值
GLU(mmol/L)	4.82(4.50,5.18)	5.45(4.97,6.33)^△	5.81(4.55,6.58)^△	12.59	<0.01
TG(mmol/L)	1.13(0.90,1.62)	1.42(0.97,2.32)	2.33(1.70,3.26)^△▲	25.17	<0.01
CHOL(mmol/L)	5.31(4.74,6.28)	5.26(4.40,6.00)	6.47(5.29,7.71)^△▲	13.18	<0.01
HDL-C(mmol/L)	1.54±0.32	1.36±0.34^△	1.32±0.88^△	8.79	<0.01
LDL-C(mmol/L)	3.08±0.79	3.34±0.88	3.48±0.95^*	3.07	0.039
APO-A(g/L)	1.41(1.33,1.49)	1.35(1.32,1.51)	1.89(1.79,1.98)^△▲	115.30	<0.01
APO-B(g/L)	1.07(1.03,1.11)	1.04(0.84,1.11)	1.37(1.17,1.64)^△▲	34.67	<0.01
LPa(mg/dl)	7.60(5.27,9.32)	8.70(4.00,16.15)	10.2(8.25,11.95)^△#	15.25	<0.01
TP(g/L)	69.06±12.13	65.82±8.47	61.38±5.85^△#	9.48	<0.01
ALB(g/L)	36.20±5.29	37.47±7.39	33.63±6.07	2.23	0.106
ALT(U/L)	16.50(13.00,22.75)	17.00(12.59,23.68)	17.21(9.87,24.21)	0.10	0.905
AST(U/L)	23.00(20.25,27.01)	23.12(20.00,27.25)	22.36(20.21,29.36)	0.28	0.758
CR(μmol/L)	67.65(57.67,79.87)	72.90(57.52,91.47)	74.8(66.47,83.95)	2.16	0.118
UREA(mmol/L)	5.66(4.59,6.46)	5.79(4.63,6.89)	5.73(4.81,6.94)	0.10	0.902
UA(μmol/L)	323.01(294.24,401.14)	359.82(286.25,426.75)	358.48(270.25,414.51)	2.70	0.069

指标	BD-NM(n=58)		BD-M(n=52)
	FGF1		FGF1
		r值	P值	r值	P值
BMI	0.196	0.141	-0.127	0.370
SDP(mmHg)	-0.167	0.209	-0.02	0.889
BDP(mmHg)	-0.174	0.191	0.017	0.902
GLU(mmol/L)	0.115	0.389	0.834	<0.01
TG(mmol/L)	-0.031	0.814	0.735	<0.01
CHOL(mmol/L)	0.15	0.26	0.727	<0.01
HDL-C(mmol/L)	-0.122	0.361	0.261	0.062
LDL-C(mmol/L)	-0.077	0.563	0.523	<0.01
APO-A(g/L)	0.092	0.494	0.217	0.122
APO-B(g/L)	-0.163	0.223	0.293	0.035
LPa(mg/dL)	0.074	0.58	0.234	0.096
TP(g/L)	0.161	0.226	-0.417	0.002
ALB(g/L)	-0.015	0.912	0.03	0.831
ALT(U/L)	0.182	0.172	-0.104	0.464
AST(U/L)	0.256	0.052	-0.167	0.235
CR(μmol/L)	0.218	0.101	-0.035	0.803
UREA(mmol/L)	0.035	0.793	0.028	0.842
UA(μmol/L)	-0.021	0.874	0.012	0.930