紫绀型先天性心脏病患儿瘦素及其受体的表达与低氧诱导因子-1α相关

doi:10.16352/j.issn.1001-6325.2024.02.0225

基础医学与临床 ›› 2024, Vol. 44 ›› Issue (2): 225-230.doi: 10.16352/j.issn.1001-6325.2024.02.0225

紫绀型先天性心脏病患儿瘦素及其受体的表达与低氧诱导因子-1α相关

国蓉¹, 张森², 袁建辉², 李肖珏¹, 周姝含¹, 李守军², 陈燕燕^1*

中国医学科学院北京协和医学院阜外医院 1.内分泌科; 2.小儿心脏外科一病区,北京 100037

收稿日期:2023-04-18 修回日期:2023-11-23 发布日期:2024-02-05
通讯作者: ^*doc.yan@medmail.com.cn
基金资助:
阜外医院青年基金项目(2022-FWQN12); 中国医学科学院医学与健康科技创新工程项目(2020-I2M-C&T-A-009); 阜外医院特色学科发展项目(2022-FWTS06)

Expression of leptin and its receptor correlates with hypoxia- inducible factor-1α in infants with cyanotic congenital heart disease

GUO Rong¹, ZHANG Sen², YUAN Jianhui², LI Xiaojue¹, ZHOU Shuhan¹, LI Shoujun², CHEN Yanyan^1*

1. Department of Endocrine; 2. the First Division of Department of Pediatric Cardiac Surgery, Fuwai Hospital, CAMS & PUMC, Beijing 100037, China

Received:2023-04-18 Revised:2023-11-23 Published:2024-02-05
Contact: ^*doc.yan@medmail.com.cn

摘要/Abstract

摘要： 目的探讨低龄紫绀型先天性心脏病(先心病)患儿血清瘦素(LEP)水平与患儿身体质量指数(BMI)的相关性,以及瘦素及其受体(Ob-R)与低氧诱导因子-1α(HIF-1α)在心肌中的关联机制。方法本研究纳入了2019年1月至2020年10月于中国医学科学院阜外医院先心病外科接受手术治疗的52例低龄(6月龄以下)的先心病患儿,根据动脉血氧分压90 mmHg为界分为紫绀组(n=30)和非紫绀组(n=22)。收集其身高、体质量计算BMI值。用ELISA测定患儿血清瘦素水平, RT-qPCR及Western blot检测心肌组织HIF-1α、Ob-R表达。同期将SD大鼠分为常氧组和低氧(10% O₂)组,持续低氧4周,于低氧第14天至第21天每天腹腔注射HIF-1α抑制剂地高辛(2 mg/kg)为地高辛组。记录大鼠体质量,通过RT-qPCR及Western blot检测心肌组织HIF-1α、Ob-R的表达。结果与非紫绀组相比,紫绀组患儿BMI显著降低(P＜0.05),经BMI校正的瘦素水平(LEP/BMI)也明显低于非紫绀组(P＜0.05),Spearman相关性检验证实患儿循环系统中血清瘦素与BMI呈正相关(P＜0.05);紫绀组患儿心肌中随着HIF-1α的表达增加,Ob-R表达水平也相应增加,两者呈显著相关性(P＜0.05);动物模型中低氧动物注射地高辛后,随着HIF-1α的表达下调后,心肌组织Ob-R水平也明显低于对照组(P＜0.05),体质量下降的趋势明显减弱(P＜0.05),右室肥厚指数显著低于注射0.9%氯化钠溶液组(P＜0.05)。结论 HIF-1α可调节心肌组织中Ob-R的表达,其与瘦素及其受体的关联机制可作为改善低龄先心病患儿预后的新治疗靶点。

关键词: 先天性心脏病, 瘦素, 瘦素受体, 低氧诱导因子-1α

Abstract: Objective To investigate the correlation between serum leptin level and body mass index (BMI) in infants with cyanosis congenital heart disease, and the relationship between leptin and Ob gene receptor (Ob-R) and hypoxia-inducible factor 1α (HIF-1α) in myocardium. Methods A total of 52 children under 6 months of age with congenital heart disease who underwent surgical treatment in the Department of Congenital Heart Surgery, Fuwai Hospital from January 2019 to October 2020 were included in this study. According to the arterial partial pressure of oxygen (PaO₂) of 90 mmHg, they were divided into cyanotic group (n=30) and acyanotic group (n=22). Their height and weight were collected to calculate BMI. The serum leptin level was measured by ELISA. The expressions of HIF-1α and Ob-R in myocardial tissue were detected by RT-PCR and Western blot. In animal model, SD rats were divided into normoxia group and hypoxia intervention group, which were subjected to continuous hypoxia (10% O₂) for 4 weeks. The hypoxia intervention group received intraperitoneal injection of HIF-1α inhibitor digoxin (2 mg/kg) daily from the 14 th to 21st day of hypoxia, respectively. The body weight of rats was recorded, and the expressions of HIF-1α and Ob-R were detected by RT-qPCR and Western blot. Results Compared with the acyanosis group, the cyanosis group had a significantly lower BMI (P＜0.05) and a lower leptin/BMI ratio (leptin /BMI) (P＜0.05). Spearman correlation analysis confirmed that serum leptin in the circulatory system was positively correlated with BMI (P＜0.05). In the cyanosis group, the expression of Ob-R increased with the upregulation of HIF-1α,showing a positive correlation. In animal model, with the down-regulation of HIF-1α expression in digoxin injection, the Ob-R level was significantly lower than that in the control group(P＜0.05), the trend of weight loss was significantly inhibited(P＜0.05). The right ventricular hypertrophy index was significantly lower than that in the control group (P＜0.05). Conclusions HIF-1α regulates the expression of Ob-R in myocardial tissue, and the mechanism of its association with leptin and Ob-R may help to find new therapeutic target for improving the prognosis of infants with congenital heart disease.

Key words: congenital heart disease, leptin, Ob gene receptor, hypoxia-inducible factor 1α

中图分类号:

R364.4

国蓉, 张森, 袁建辉, 李肖珏, 周姝含, 李守军, 陈燕燕. 紫绀型先天性心脏病患儿瘦素及其受体的表达与低氧诱导因子-1α相关[J]. 基础医学与临床, 2024, 44(2): 225-230.

GUO Rong, ZHANG Sen, YUAN Jianhui, LI Xiaojue, ZHOU Shuhan, LI Shoujun, CHEN Yanyan. Expression of leptin and its receptor correlates with hypoxia- inducible factor-1α in infants with cyanotic congenital heart disease[J]. Basic & Clinical Medicine, 2024, 44(2): 225-230.

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紫绀型先天性心脏病患儿瘦素及其受体的表达与低氧诱导因子-1α相关

Expression of leptin and its receptor correlates with hypoxia- inducible factor-1α in infants with cyanotic congenital heart disease

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