中国组织工程研究

中国组织工程研究 ›› 2026, Vol. 30 ›› Issue (18): 4649-4662.doi: 10.12307/2026.750

• 组织构建实验造模 experimental modeling in tissue construction • 上一篇    下一篇

光暴露对心力衰竭模型大鼠神经递质释放的影响及其分子机制

阮  琳1，李  佳1，施丽南1，朱  红1，吴东宁2，3，郑  迪1，李雨鹏1，赵  妍1   

  1. 1辽宁中医药大学附属第二医院，辽宁省沈阳市  110000；2中国中医科学院广安门医院西单门诊部，北京市  100031；3澳门科技大学中医药学院及中药质量研究国家重点实验室，中国澳门特别行政区  999078
  • 收稿日期:2025-08-08 修回日期:2025-10-09 出版日期:2026-06-28 发布日期:2025-12-04
  • 通讯作者: 李雨鹏，硕士，主任医师，辽宁中医药大学附属第二医院，辽宁省沈阳市 110000 并列通讯作者：赵妍，博士，副主任医师，辽宁中医药大学附属第二医院，辽宁省沈阳市 110000
  • 作者简介:阮琳，女，1983年生，辽宁省铁岭市人，汉族，2009年辽宁中医药大学毕业，硕士，主任医师，主要从事心血管内科的研究。
  • 基金资助:
    兴辽英才计划-青年拔尖人才(XLYC2007076)，项目负责人：阮琳

Effects and molecular mechanisms of light exposure on neurotransmitter release in a rat model of heart failure

Ruan Lin1, Li Jia1, Shi Linan1, Zhu Hong1, Wu Dongning2, 3, Zheng Di1, Li Yupeng1, Zhao Yan1   

  1. 1The Second Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang 110000, Liaoning Province, China; 2Xidan Outpatient, Guang’anmen Hospital, Chinese Academy of Chinese Medical Sciences, Beijing 100031, China; 3School of Chinese Medicine & State Key Laboratory of Mechanism and Quality of Chinese Medicine, Macau University of Science and Technology, Macao Special Administrative Region 999078, China 
  • Received:2025-08-08 Revised:2025-10-09 Online:2026-06-28 Published:2025-12-04
  • Contact: Li Yupeng, MS, Chief physician, The Second Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang 110000, Liaoning Province, China Co-corresponding author: Zhao Yan, PhD, Associate chief physician, The Second Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang 110000, Liaoning Province, China
  • About author:Ruan Lin, MS, Chief physician, The Second Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang 110000, Liaoning Province, China
  • Supported by:
    Xingliao Talent Program - Outstanding Young Talent Program, No. XLYC2007076 (to RL)

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摘要：



文题释义：
内源性抗氧化系统：是指生物体内自身产生和调节的一系列抗氧化机制，用于抵御氧化应激损伤。这些机制包括抗氧化酶(如超氧化物歧化酶、过氧化氢酶、谷胱甘肽过氧化物酶)、抗氧化小分子(如谷胱甘肽)以及调控这些抗氧化基因表达的转录因子。
Ca²⁺超敏化：是指细胞内钙离子对某些生理或病理过程的敏感性显著增加的现象。这种超敏化可能通过改变钙离子的结合亲和力、调节钙离子通道的活性或影响钙依赖性蛋白的功能来实现。

背景：心力衰竭发生发展与神经内分泌系统的异常激活密切相关。研究表明光暴露能够降低大鼠大脑中的多巴胺水平，进一步增强下丘脑室旁核内多巴胺能神经元的活动，从而促进促肾上腺皮质激素释放因子的释放。现并无直接证据证实光暴露会诱发心力衰竭。
目的：探究光暴露对心力衰竭模型大鼠神经递质释放的影响及其分子机制，并进行细胞学验证。
方法：①动物实验：将行心力衰竭造模的SD大鼠分为模型组、光暴露模型组、光暴露治疗组，将假手术大鼠分为光暴露对照组和空白组，每组各6只。8周实验结束后，使用ELISA检测光暴露对心衰大鼠血清神经递质、激素水平的影响，苏木精-伊红染色观察心脏病理变化；Western Blot检测核因子E2相关因子2/血红素氧化酶1/磷酸酰胺腺嘌呤二核苷酸醌氧化还原酶1信号通路的调节作用。②细胞实验：将小鼠心肌细胞(HL-1细胞)分为空白组、5-羟色胺高剂量对照组(5-羟色胺500 mg/mL)、脂多糖低剂量组(脂多糖1 μg/mL)、 脂多糖+5-羟色胺高剂量组(5-羟色胺500 mg/mL+ 脂多糖1 μg/mL)、ML385组(脂多糖1 μg/mL+ 5-羟色胺500 mg/mL+核因子E2相关因子2抑制剂ML385为
2.5 μg/mL)、白藜芦醇组(脂多糖1 μg/mL+ 5-羟色胺500 mg/mL+ 核因子E2相关因子2激动剂白藜芦醇30 μg/mL)，干预36 h，考察各干预条件对于细胞增殖的影响，利用Western Blot方法，验证5-羟色胺对HL-1细胞核因子E2相关因子2/血红素氧化酶1/磷酸酰胺腺嘌呤二核苷酸醌氧化还原酶1信号轴的影响。
结果与结论：①光暴露能提升心力衰竭模型大鼠血清中的去甲肾上腺素和5-羟色胺水平，加剧心脏损伤；光暴露模型组及模型组心肌组织病理均呈现了明显的损伤，细胞出现了肿胀、核皱缩、空泡等现象；光暴露治疗组大鼠心肌细胞的损伤得到了明显的缓解；光暴露对照组的血管紧张素转换酶2蛋白表达低于空白组(P < 0.05)而高于模型组(P < 0.05)，而Mas、c-fos及血红素氧化酶1表达与空白组相比虽有所下调，但差异无显著性意义(P > 0.05)。在光暴露模型组中，血管紧张素转换酶2、Mas、核因子 E2 相关因子2及血红素氧化酶1蛋白表达均较空白组显著下调(P < 0.05)。与光暴露模型组相比，光暴露治疗组中核因子E2相关因子2/血红素氧化酶1/磷酸酰胺腺嘌呤二核苷酸醌氧化还原酶1信号通路相关蛋白表达均明显上调(P < 0.05)。②细胞实验显示5-羟色胺增加了脂多糖所致的心肌细胞损伤，且该损伤效应与核因子E2相关因子2/血红素氧化酶1/磷酸酰胺腺嘌呤二核苷酸醌氧化还原酶1信号通路的抑制相关。结论：过度的光暴露可能通过调节神经递质组成，介导核因子E2相关因子2/血红素氧化酶1/磷酸酰胺腺嘌呤二核苷酸醌氧化还原酶1信号通路，加速心力衰竭的进程。 

https://orcid.org/0009-0006-3305-4357(阮琳)


中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程

关键词: 光暴露, 心力衰竭, 神经递质, 5-羟色胺, 心肌细胞损伤, 核因子E2相关因子2

Abstract: BACKGROUND: The development and progression of heart failure are closely related to abnormal activation of the neuroendocrine system. Studies have demonstrated that light exposure decreases dopamine levels in the rat brain, increases the activity of dopaminergic neurons in the paraventricular nucleus of the hypothalamus, and stimulates the release of corticotropin releasing factor. However, there is currently no direct evidence proving that light exposure induces heart failure.
Objective: To investigate the effect and molecular mechanism of light exposure on neurotransmitter release in heart failure model rats, and to conduct cytological verification.
Methods: (1) Animal experiment: Sprague-Dawley rats with heart failure were divided into model, light exposure model, and light exposure treatment groups, while shamsurgery rats were divided into light exposure control and blank groups, with six rats in each group. After 8-week experiment, enzyme linked immunosorbent assay was used to detect the effects of light exposure on serum levels of neurotransmitter and hormone in heart failure rats. Hematoxylin-eosin staining was used to detect pathological changes in the heart. Western blot assay was used to detect the regulatory effects of nuclear factor E2 related factor 2/heme oxidase 1/NADPH quinineoxidoreductase-1 signaling pathway. (2) Cell experiment: Mouse cardiomyocytes (HL-1 cells) were divided into blank, high-dose 5-hydroxytryptamine control (5-hydroxytryptamine 500 mg/mL), low-dose lipopolysaccharide (lipopolysaccharide 1 μg/mL), lipopolysaccharide + high-dose 5-hydroxytryptamine (5-hydroxytryptamine 500 mg/mL + lipopolysaccharide 1 μg/mL), ML385 (lipopolysaccharide 1 μg/mL + 5-hydroxytryptamine 500 mg/mL + nuclear factor E2 related factor 2 inhibitor ML385 2.5 μg/mL), and resveratrol (lipopolysaccharide 1 μg/mL + 5-hydroxytryptamine 500 mg/mL + 
nuclear factor E2 related factor 2 agonist resveratrol 30 μg/mL) groups. After 36-hour intervention, the effects of various intervention conditions on cell proliferation were investigated. Western blot assay was used to verify the effect of 5-hydroxytryptamine on nuclear factor E2 related factor 2/heme oxidase 1/NADPH quinineoxidoreductase-1 signaling axis in HL-1 cells.
Results and conclusion: (1) Animal experiment: Light exposure increases the serum levels of norepinephrine and 5-hydroxytryptamine in heart failure model rats, thereby exacerbating heart damage. Both light exposure model and model groups showed significant pathological damage to the myocardial tissue, including swelling, nuclear shrinkage, and the formation of vacuoles. However, the damage to myocardial cells in the light exposure treatment group was significantly alleviated. In the light exposure control group, the level of angiotensin converting enzyme 2 protein expression was lower than that in the blank group (P < 0.05), but higher than that in the model group (P < 0.05). Although Mas, c-fos, and heme oxygenase-1 expression levels were downregulated compared to the blank group, but these differences were not statistically significant (P > 0.05). In the light-exposed model group, the protein expression levels of angiotensin converting enzyme 2, Mas, nuclear factor E2 related factor 2, and heme oxygenase-1 were significantly downregulated compared to the blank group (P < 0.05). Compared with the light exposure model group, the expression level of proteins related to the nuclear factor E2 related factor 2/heme oxygenase-1/NADPH quinineoxidoreductase-1 signaling pathway was significantly upregulated in the light exposure treatment group (P < 0.05). (2) Cell experiments: 5-Hydroxytryptamine increased lipopolysaccharide-induced myocardial cell damage. This damage was associated with the inhibition of the nuclear factor E2 related factor 2/heme oxidase 1/NADPH quinineoxidoreductase-1 signaling pathway. Conclusion: Excessive light exposure may accelerate the progression of heart failure by regulating neurotransmitter composition, mediating the nuclear factor E2 related factor 2/heme oxidase 1/NADPH quinineoxidoreductase-1 signaling pathway.  


Key words: light exposure, heart failure, neurotransmitter, 5-hydroxytryptamine, myocardial cell injury, nuclear factor E2 related factor 2

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