Expression and correlation of liver macrophage migration inhibitory factor in patients with OSA combined with NAFLD

SUN Yuechen; LIN Zehua; CAI Weisong; YANG Xiuping; CHEN Xiong

doi:10.14188/j.1671-8852.2024.0043

您当前的位置：

首页 >

文章列表页 >

Expression and correlation of liver macrophage migration inhibitory factor in patients with OSA combined with NAFLD

更新时间：2026-11-05

- Expression and correlation of liver macrophage migration inhibitory factor in patients with OSA combined with NAFLD
- Medical Journal of Wuhan University Vol. 46, Issue 3, Pages: 350-356(2025)
- 作者机构：
  
  武汉大学中南医院耳鼻咽喉头颈外科/睡眠医学中心湖北武汉 430071
- 作者简介：
- 基金信息：
- DOI：10.14188/j.1671-8852.2024.0043
  CLC： R766
- Received：17 January 2024，
  
  Published：25 March 2025
- 稿件说明：
移动端阅览
孙月晨,林泽华,蔡伟松等.肝脏巨噬细胞迁移抑制因子在OSA合并非酒精性脂肪肝病患者中的表达及相关性研究[J].武汉大学学报（医学版）,2025,46(03):350-356.

SUN Yuechen,LIN Zehua,CAI Weisong,et al.Expression and correlation of liver macrophage migration inhibitory factor in patients with OSA combined with NAFLD[J].Medical Journal of Wuhan University,2025,46(03):350-356.
孙月晨,林泽华,蔡伟松等.肝脏巨噬细胞迁移抑制因子在OSA合并非酒精性脂肪肝病患者中的表达及相关性研究[J].武汉大学学报（医学版）,2025,46(03):350-356. DOI： 10.14188/j.1671-8852.2024.0043.

SUN Yuechen,LIN Zehua,CAI Weisong,et al.Expression and correlation of liver macrophage migration inhibitory factor in patients with OSA combined with NAFLD[J].Medical Journal of Wuhan University,2025,46(03):350-356. DOI： 10.14188/j.1671-8852.2024.0043.

摘要

目的

探讨肝脏巨噬细胞迁移抑制因子(MIF)在阻塞性睡眠呼吸暂停(OSA)合并非酒精性脂肪肝病(NAFLD)患者中的表达及临床意义。

方法

选取2019年10月至2022年5月在武汉大学中南医院因代谢综合征就诊的患者50例，对其进行多导睡眠监测，根据呼吸暂停低通气指数(AHI)将其分为4组：①无OSA合并NAFLD组（对照组，7例），②轻度OSA合并NAFLD组（15例），③中度OSA合并NAFLD组（12例），④重度OSA合并NAFLD组（16例），采集血清和肝脏标本，分别应用酶联免疫吸附法和免疫组织化学染色，评估患者血清和肝脏中MIF的表达水平，分析MIF水平与OSA合并NAFLD严重程度及睡眠相关指标的相关性。

结果

与对照组相比，OSA合并NAFLD患者的血清及肝脏MIF表达水平升高，且其与OSA严重程度呈正相关。在校正体质量指数（BMI）之后，血清MIF浓度与OSA严重程度仍呈正相关（

0.05）。Logistic回归分析显示，OSA是NAFLD的独立危险因素。相关性分析显示，血清MIF水平与NAFLD严重程度呈正相关（

0.374

，P=

0.007），校正BMI之后，血清MIF水平与NAFLD严重程度仍呈正相关（

0.314，

0.028）。血清MIF水平与AHI、氧减指数（ODI）呈正相关（

0.337，

0.017；

0.292，

0.040），与LSaO

呈负相关（

r=-

0.281，

0.048）。采用偏相关

分析校正BMI后，血清MIF水平与睡眠监测指标均无相关性（

0.05）。

结论

OSA合并NAFLD疾病严重程度与MIF水平密切相关，OSA可能通过慢性间歇性缺氧刺激肝细胞释放MIF，促进NAFLD的发展。

Abstract

Objective

To explore the expression and clinical significance of liver macrophage migration inhibitory factor (MIF) in patients with obstructive sleep apnea (OSA) combined with nonalcoholic fatty liver disease (NAFLD).

Methods

Fifty patients with metabolic syndrome who were treated at Zhongnan Hospital of Wuhan University from October 2019 to May 2022 were selected

and polysomnography was performed on them. According to the apnea‑hypopnea index (AHI) index the patients were divided into four groups: ① no OSA combined with NAFLD group (7 cases)

② mild OSA combined with NAFLD group (15 cases)

③ moderate OSA combined with NAFLD group (12 cases)

and ④ severe OSA combined with NAFLD group (16 cases)

and their serum and liver specimens were collected. Enzyme‑linked immunosorbent assay and immunohistochemical staining were adopted respectively to evaluate the expression levels of MIF in the patients' serum and liver

and the relationship between MIF levels and the severity of NAFLD and sleep‑related indicators was analyzed.

Results

Compared with the control group

the patients with OSA combined with NAFLD had elevated serum and hepatic MIF expression levels

and MIF levels were positively correlated with OSA severity. After correcting for BMI

serum MIF concentration remained positively correlation with OSA severity (

0.05). Logistic regression analysis showed that OSA was an independent risk factor for NAFLD. Correlation analysis showed that serum MIF levels were positively correlated with NAFLD severity

(r=

0.374

0.007) and remained positively correlated with NAFLD severity after correction for BMI (

0.314

028). Serum MIF levels were positively correlated with AHI and ODI (

0.337

0.017;

0.292

0.040) and negatively correlated with LSaO

(

r=-

0.281

0.048). After correcting for BMI

there was no correlation between serum MIF levels and any of the sleep monitoring indicators by partial correlation analysis (

0.05).

Conclusion

The disease severity of OSA combined with NAFLD is closely related to MIF levels

and OSA may stimulate hepatocytes to release MIF through chronic intermittent hypoxia and promote the development of NAFLD.

关键词

Keywords

references

中国医师协会睡眠医学专业委员会 . 成人阻塞性睡眠呼吸暂停多学科诊疗指南 [J ] . 中华医学杂志 , 2018 , 98 ( 24 ): 1902 ‑ 1914 .

Sleep Medicine Committee of Chinese Medical Doctors' Association . Multidisciplinary guidelines for the management of obstructive sleep apnoea in adults [ [J ] . Natl Med J China , 2018 , 98 ( 24 ): 1902 ‑ 1914 .

GUO X , YIN X , LIU Z , et al . Non‑alcoholic fatty liver disease (NAFLD) pathogenesis and natural products for prevention and treatment [J ] . Int J Mol Sci , 2022 , 23 ( 24 ): 15489 .

CHEN L D , CHEN M X , CHEN G P , et al . Association between obstructive sleep apnea and non‑alcoholic fatty liver disease in pediatric patients: A meta‑analysis [J ] . Pediatr Obes , 2021 , 16 ( 3 ): e12718 .

JULLIAN‑DESAYES I , TRZEPIZUR W , BOURSIER J , et al . Obstructive sleep apnea, chronic obstructive pulmonary disease and NAFLD: an individual participant data meta‑analysis [J ] . Sleep Med , 2021 , 77 : 357 ‑ 364 .

JI Y , LIANG Y M , MAK J C W , et al . Obstructive sleep apnea, intermittent hypoxia and non‑alcoholic fatty liver disease [J ] . Sleep Med , 2022 , 95 : 16 ‑ 28 .

SUMAIYA K , LANGFORD D , NATARAJASEENIVASAN K , et al . Macrophage migration inhibitory factor (MIF): A multifaceted cytokine regulated by genetic and physiological strategies [J ] . Pharmacol Ther , 2022 , 233 : 108024 .

LI Y , ZOU C , CHEN C , et al . Myeloid‑derived MIF drives RIPK1‑mediated cerebromicrovascular endothelial cell death to exacerbate ischemic brain injury [J ] . Proc Natl Acad Sci USA , 2023 , 120 ( 5 ): e2219091120 .

RUNDO J V , DOWNEY R . Polysomnography [J ] . Handb Clin Neurol , 2019 , 160 : 381 ‑ 392 .

中华医学会肝病学分会脂肪肝和酒精性肝病学组 , 中国医师协会脂肪性肝病专家委员会 . 酒精性肝病防治指南(2018年更新版) [J ] . 实用肝脏病杂志 , 2018 , 21 ( 2 ): 170 ‑ 176 .

National Workshop on Fatty Liver and Alcoholic Liver Disease , Chinese Society of Hepatology ; Chinese Medical Association Fatty Liver Expert Committee , Chinese Medical Doctor Association . Guidelines of prevention and treatment for alcoholic liver disease: A 2018 update [J ] . J Pract Hepatol , 2018 , 21 ( 2 ): 170 ‑ 176 .

WU X , GONG L , XIE L , et al . NLRP3 deficiency protects against intermittent hypoxia‑induced neuroinflammation and mitochondrial ROS by promoting the PINK1‑parkin pathway of mitophagy in a murine model of sleep apnea [J ] . Front Immunol , 2021 , 12 : 628168 .

PARIKH M P , GUPTA N M , MCCULLOUGH A J . Obstructive sleep apnea and the liver [J ] . Clin Liver Dis , 2019 , 23 ( 2 ): 363 ‑ 382 .

WANG F , ZOU J , XU H , et al . Effects of chronic intermittent hypoxia and chronic sleep fragmentation on gut microbiome, serum metabolome, liver and adipose tissue morphology [J ] . Front Endocrinol (Lausanne) , 2022 , 13 : 820939 .

ZHANG H J , ZHOU L , ZHOU Y H , et al . Intermittent hypoxia aggravates non‑alcoholic fatty liver disease via RIPK3‑dependent necroptosis‑modulated Nrf2/NFκB signaling pathway [J ] . Life Sci , 2021 , 285 : 119963 .

MESARWI O A , MOYA E A , ZHEN X , et al . Hepatocyte HIF‑1 and intermittent hypoxia independently impact liver fibrosis in murine nonalcoholic fatty liver disease [J ] . Am J Respir Cell Mol Biol , 2021 , 65 ( 4 ): 390 ‑ 402 .

LIANG H , YANG X J , LIU C , et al . Effect of NF‑kB signaling pathway on the expression of MIF, TNF‑α, IL‑6 in the regulation of intervertebral disc degeneration [J ] . J Musculoskelet Neuronal Interact , 2018 , 18 ( 4 ): 551 ‑ 556 .

ZHANG X , YIN C , TIAN W , et al . Effects of cognitive behavioral therapy on anxiety and depression in patients with chronic obstructive pulmonary disease: A meta‑analysis and systematic review [J ] . Clin Respir J , 2020 , 14 ( 10 ): 891 ‑ 900 .

AHMED M , MILLER E . Macrophage migration inhibitory factor (MIF) in the development and progression of pulmonary arterial hypertension [J ] . Glob Cardiol Sci Pract , 2018 , 2018 ( 2 ): 14 .

HEINRICHS D , BRANDT E F , FISCHER P , et al . Unexpected pro‑fibrotic effect of MIF in non‑alcoholic steatohepatitis is linked to a shift in NKT cell populations [J ] . Cells , 2021 , 10 ( 2 ): 252 .

CUI D , PENG Y , ZHANG C , et al . Macrophage migration inhibitory factor mediates metabolic dysfunction induced by atypical antipsychotic therapy [J ] . J Clin Invest , 2018 , 128 ( 11 ): 4997 ‑ 5007 .

KIM B S , TILSTAM P V , ARNKE K , et al . Differential regulation of macrophage activation by the MIF cytokine superfamily members MIF and MIF‑2 in adipose tissue during endotoxemia [J ] . FASEB J , 2020 , 34 ( 3 ): 4219 ‑ 4233 .

LI D Z , DUN Y S , QI D K , et al . Intermittent fasting activates macrophage migration inhibitory factor and alleviates high‑fat diet‑induced nonalcoholic fatty liver disease [J ] . Sci Rep , 2023 , 13 : 13068 .

LIU J , LI D Z , DUN Y S , et al . Rhodiola activates macrophage migration inhibitory factor to alleviate non‑alcoholic fatty liver disease [J ] . Life Sci , 2022 , 308 : 120949 .

GLIGOROVSKA L , TEOFILOVIĆ A , VOJNOVIĆ MILUTINOVIĆ D , et al . Macrophage migration inhibitory factor deficiency aggravates effects of fructose‑enriched diet on lipid metabolism in the mouse liver [J ] . Biofactors , 2021 , 47 ( 3 ): 363 ‑ 375 .

REGEV D , ETZION S , HADDAD H , et al . Obstructive sleep apnea syndrome in vitro model: Controlled intermittent hypoxia stimulation of human stem cells‑derived cardiomyocytes [J ] . Int J Mol Sci , 2022 , 23 ( 18 ): 10272 .

BHATT S P , GULERIA R , KABRA S K . Metabolic alterations and systemic inflammation in overweight/obese children with obstructive sleep apnea [J ] . PLoS One , 2021 , 16 ( 6 ): e0252353 .

宋涛 , 李晓栋 , 贾喆 . 巨噬细胞移动抑制因子在阻塞性睡眠呼吸暂停低通气综合征中的表达及与血管内皮损伤的相关性 [J ] . 临床与病理杂志 , 2020 , 40 ( 11 ): 2864 ‑ 2869 .

SONG T , LI X D , JIA Z . Expression of macrophage migration inhibitory factor in obstructive sleep apnea hypopnea syndrome and its correlation with vascular endothelial injury [J ] . J Clin Pathol Res , 2020 , 40 ( 11 ): 2864 ‑ 2869 .

周晓蕾 , 赵志国 , 袁彦丽 , 等 . 持续正压通气治疗对阻塞性睡眠呼吸暂停低通气综合征患者巨噬细胞移动抑制因子和C反应蛋白的影响 [J ] . 中华实用诊断与治疗杂志 , 2019 , 33 ( 4 ): 353 ‑ 355 .

ZHOU X L , ZHAO Z G , YUAN Y L , et al . Effect of continuous positive airway pressure therapy on macrophage migration inhibitory factor and C‑reactive protein in patients with obstructive sleep apnea hypopnea syndrome [J ] . J Chin Pract Diagn Ther , 2019 , 33 ( 4 ): 353 ‑ 355 .

MARIN V , POULSEN K , ODENA G , et al . Hepatocyte‑derived macrophage migration inhibitory factor mediates alcohol‑induced liver injury in mice and patients [J ] . J Hepatol , 2017 , 67 ( 5 ): 1018 ‑ 1025 .

Views

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Difference of pathological and physiological characteristics, comorbidities and therapy of obesity hypoventilation syndrome

Research status of the relationship between obstructive sleep apnea and metabolic syndrome

Impact of obstructive sleep apnea on cardiac diastolic dysfunction: A meta⁃analysis

Subtype characteristics of visceral adipose tissue infiltration in obstructive sleep apnea patients and their correlations with glycolipid metabolic disorders

Application effect of moxibustion combined with phototherapy in patients with diabetic foot

Related Author

HU Ke

HAO Yueying

SONG Yan

HE Xin

HU Ke

WANG Yanggan

TIAN Haiyan

SUN Xiaoqi

Related Institution

Second Dept. of Respiratory and Critical Care Medicine, Renmin Hospital of Wuhan University

Dept. Ⅱ of Respiratory and Critical Care Medicine， Renmin Hospital of Wuhan University

Department of Geriatrics, Zhongnan Hospital of Wuhan University

Department of Otolaryngology, Zhongnan Hospital of Wuhan University

Dept. of Respiratory and Critical Care Medicine，Renmin Hospital of Wuhan University

AI问答

⁰