大黄素改善高糖诱导海马神经元线粒体自噬障碍的研究

doi:10.11958/20252781

天津医药 ›› 2026, Vol. 54 ›› Issue (5): 449-454.doi: 10.11958/20252781

• 细胞与分子生物学 • 下一篇

大黄素改善高糖诱导海马神经元线粒体自噬障碍的研究

何玉¹(), 孙宇², 张艺琼³^,⁴, 许永劼³^,⁴, 王双⁵, 潘卫³^,⁴, 任智晶^1△()

¹ 贵州省人民医院检验科（邮编 550002）
² 贵州医科大学附属医院输血科
³ 贵州医科大学附属医院贵州省产前诊断中心
⁴ 贵州医科大学公共卫生与健康学院
⁵ 上海交通大学医学院附属上海儿童医学中心贵州医院检验科

收稿日期:2025-08-24 修回日期:2025-11-07 出版日期:2026-05-15 发布日期:2026-05-13
通讯作者: ^△E-mail：rzj123276719@163.com
作者简介:何玉（1986），女，主管技师，主要从事糖尿病及其并发症方面研究。E-mail：hey0866@sina.com
基金资助:
国家自然科学基金资助项目(82260165);国家自然科学基金资助项目(82300920);贵州省科技计划项目(黔科合基础-ZK[2024]一般199);贵州省科技计划项目(黔科合基础-ZK[2023]一般209);贵州省科技计划项目(黔科合基础MS[2026]355);贵州省卫生健康委科学技术基金(gzwkj2024-081);贵州省卫生健康委科学技术基金(gzwkj2024-170)

Research on emodin improving high glucose-induced mitophagy impairment in hippocampal neurons

HE Yu¹(), SUN Yu², ZHANG Yiqiong³^,⁴, XU Yongjie³^,⁴, WANG Shuang⁵, PAN Wei³^,⁴, REN Zhijing^1△()

¹ Department of Clinical Laboratory, Guizhou Provincial People's Hospital, Guiyang 550002, China
² Department of Blood Transfusion, Affiliated Hospital of Guizhou Medical University
³ Guizhou Provincial Prenatal Diagnosis Center, Affiliated Hospital of Guizhou Medical University
⁴ School of Public Health and Health, Guizhou Medical University
⁵ Department of Clinical Laboratory, Guizhou Hospital of Shanghai Children's Medical Center Affiliated to Shanghai Jiaotong University School of Medicine

Received:2025-08-24 Revised:2025-11-07 Published:2026-05-15 Online:2026-05-13
Contact: ^△E-mail：rzj123276719@163.com

何玉, 孙宇, 张艺琼, 许永劼, 王双, 潘卫, 任智晶. 大黄素改善高糖诱导海马神经元线粒体自噬障碍的研究[J]. 天津医药, 2026, 54(5): 449-454.

HE Yu, SUN Yu, ZHANG Yiqiong, XU Yongjie, WANG Shuang, PAN Wei, REN Zhijing. Research on emodin improving high glucose-induced mitophagy impairment in hippocampal neurons[J]. Tianjin Medical Journal, 2026, 54(5): 449-454.

摘要/Abstract

摘要：

目的探讨何首乌有效成分大黄素抑制组蛋白乙酰转移酶2A（KAT2A）对高糖环境下海马神经元线粒体自噬障碍的保护作用及其潜在分子机制。方法采用高糖诱导海马神经元建立体外模型，通过大黄素干预后，分别检测细胞活力、乳酸脱氢酶（LDH）含量、组蛋白乙酰转移酶（HAT）含量、活性氧（ROS）水平、线粒体膜电位变化，并采用Western blot与RT-qPCR检测线粒体自噬相关微管相关蛋白1轻链3-Ⅱ（LC3-Ⅱ）、P62、PTEN诱导假定激酶1（PINK1）、KAT2A蛋白及mRNA的表达情况，运用分子对接技术分析大黄素与KAT2A之间的结合能力。结果大黄素处理能显著提升高糖条件下神经元的细胞活力，同时降低LDH漏出率、HAT及细胞内ROS水平，并有效缓解线粒体膜电位下降。此外，Western blot与RT-qPCR结果表明大黄素干预后KAT2A、P62、PINK1蛋白及mRNA表达水平明显下调，LC3-Ⅱ蛋白及mRNA表达上调。分子对接结果进一步揭示，大黄素与KAT2A之间存在较好的结合活性，结合能为-32.6 kJ/mol。结论大黄素能够有效减轻高糖引起的海马神经元线粒体自噬功能障碍，减少ROS与LDH的生成，其作用机制可能与抑制组蛋白乙酰转移酶KAT2A的活性有关。

关键词: 大黄素, 组蛋白酰基转移酶, 海马, 神经元, 线粒体, 自噬

Abstract:

Objective To investigate the protective effect of emodin, an active component of polygonum multiflorum, against mitochondrial autophagy dysfunction in hippocampal neurons under high-glucose conditions by inhibiting histone acetyltransferase 2A (KAT2A), and its potential molecular mechanism. Methods An in vitro model was established by inducing hippocampal neurons with high glucose. Following intervention with emodin, cell viability, lactate dehydrogenase (LDH) content, histone acetyltransferase (HAT) content and reactive oxygen species (ROS) levels were measured, and mitochondrial membrane potential changes were also detected. Western blot assay and RT-qPCR were employed to assess the expression of mitochondrial autophagy-related proteins, including microtubule-associated protein 1 light chain 3-Ⅱ(LC3-Ⅱ), P62, PTEN-induced prokinase 1 (PINK1), KAT2A and their corresponding mRNAs. Molecular docking analysis was conducted to evaluate the binding affinity between emodin and KAT2A. Results Emodin treatment significantly enhanced neuronal viability under high-glucose conditions, while reducing LDH leakage, HAT and intracellular ROS levels, and effectively mitigated mitochondrial membrane potential decline. Additionally, Western blot assay and RT-qPCR results demonstrated that after emodin intervention, the expression levels of KAT2A, P62 and PINK1 proteins and mRNA were significantly downregulated, while LC3-Ⅱ protein and mRNA expression were upregulated. Molecular docking results further revealed that emodin exhibited good binding activity with KAT2A, with a binding energy of -32.6 kJ/mol. Conclusion This study demonstrates that emodin can effectively alleviate high glucose-induced mitophagy dysfunction in hippocampal neurons and reduce the generation of ROS and LDH. The underlying mechanism may be associated with the inhibition of KAT2A activity.

Key words: emodin, histone acetyltransferases, hippocampus, neurons, mitochondria, autophagy

中图分类号:

R587.25

图/表 7

参考文献 30

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基因名称	引物序列（5′→3′）	产物大小/bp
KAT2A	上游：TAGCTGTGAGCACCCTTTGG	107
	下游：TTCCTCTTCTCCCCTGGCAT	107
LC3-Ⅱ	上游：GATGTCCGACTTATTCGAGAGC	82
	下游：TTGAGCTGTAAGCGCCTTCTA	82
P62	上游：GGACCCATCTACAGAGGCTG	96
	下游：TTCTGGACTGCTGGTGCAAT	96
PINK1	上游：GAGTGGGACTCAGATGGCTG	92
	下游：GCACATTTGCAGCTAAGCGT	92
β-actin	上游：GTGACGTTGACATCCGTAAAGA	114
	下游：GTAACAGTCCGCCTAGAAGCAC	114

基因名称	引物序列（5′→3′）	产物大小/bp
KAT2A	上游：TAGCTGTGAGCACCCTTTGG	107
	下游：TTCCTCTTCTCCCCTGGCAT	107
LC3-Ⅱ	上游：GATGTCCGACTTATTCGAGAGC	82
	下游：TTGAGCTGTAAGCGCCTTCTA	82
P62	上游：GGACCCATCTACAGAGGCTG	96
	下游：TTCTGGACTGCTGGTGCAAT	96
PINK1	上游：GAGTGGGACTCAGATGGCTG	92
	下游：GCACATTTGCAGCTAAGCGT	92
β-actin	上游：GTGACGTTGACATCCGTAAAGA	114
	下游：GTAACAGTCCGCCTAGAAGCAC	114

组别	细胞活力/%	LDH（U/L）
对照组	100.00±2.79	0.313 4±0.004 6
高糖组	67.23±3.99^a	0.353 8±0.004 8^a
高糖组+大黄素组	84.06±4.06^ab	0.339 8±0.008 8^ab
F	204.400^＊＊	112.300^＊＊
组别	ROS		HAT（μg/L）
对照组	444.33±34.67		0.48±0.47
高糖组	1 227.33±157.67^a		1.31±0.02^a
高糖组+大黄素组	840.67±76.67^ab		0.88±0.03^ab
F	151.400^＊＊		5 101.000^＊＊

组别	细胞活力/%	LDH（U/L）
对照组	100.00±2.79	0.313 4±0.004 6
高糖组	67.23±3.99^a	0.353 8±0.004 8^a
高糖组+大黄素组	84.06±4.06^ab	0.339 8±0.008 8^ab
F	204.400^＊＊	112.300^＊＊
组别	ROS		HAT（μg/L）
对照组	444.33±34.67		0.48±0.47
高糖组	1 227.33±157.67^a		1.31±0.02^a
高糖组+大黄素组	840.67±76.67^ab		0.88±0.03^ab
F	151.400^＊＊		5 101.000^＊＊

组别		线粒体膜电位		KAT2A
对照组		1.84±0.17		1.00±0.00
高糖组		0.55±0.11^a		1.47±0.15^a
高糖组+大黄素组		1.20±0.07^ab		0.76±0.11^ab
F		92.810^＊＊		44.920^＊＊
组别	LC3-Ⅱ		P62		PINK1
对照组	1.00±0.00		1.00±0.00		1.00±0.00
高糖组	0.75±0.25		1.38±0.15		1.53±0.13^a
高糖组+大黄素组	1.43±0.28^b		0.76±0.37^b		0.73±0.21^b
F	10.010^＊		7.129^＊		25.180^＊＊

大黄素改善高糖诱导海马神经元线粒体自噬障碍的研究

Research on emodin improving high glucose-induced mitophagy impairment in hippocampal neurons

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组别	KAT2A	LC3-Ⅱ	P62	PINK1
对照组	0.85±0.09	0.82±0.08	0.83±0.12	0.75±0.15
高糖组	1.09±0.08^a	0.54±0.04^a	1.25±0.38	1.04±0.14
高糖组+大黄素组	0.57±0.06^ab	1.05±0.09^ab	0.46±0.07^b	0.60±0.15^b
F	39.660^＊＊	50.620^＊＊	11.200^＊＊	8.697^＊

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