人参皂苷Rg1在IL-6诱导的大鼠神经元铁死亡中的作用

doi:10.11958/20231989

天津医药 ›› 2024, Vol. 52 ›› Issue (11): 1137-1140.doi: 10.11958/20231989

人参皂苷Rg1在IL-6诱导的大鼠神经元铁死亡中的作用

黄晓蕾(), 葛婷婷, 赵俊松, 倪志华^△()

上海市宝山区中西医结合医院放射科（邮编201900）

收稿日期:2024-01-02 修回日期:2024-05-24 出版日期:2024-11-15 发布日期:2024-11-12
通讯作者: △E-mail：19713115@qq.com
作者简介:黄晓蕾（1989），女，主治医师，主要从事缺血性脑卒中防治研究。E-mail：kyuhuang0301@163.com
基金资助:
上海市宝山区科学技术委员会科技创新专项资金项目(2023-E-17);上海市宝山区卫生健康委员会优青计划(BSWSYC-2023-04)

Study on the role of ginsenoside Rg1 in IL-6-induced neuronal ferroptosis in rats

HUANG Xiaolei(), GE Tingting, ZHAO Junsong, NI Zhihua^△()

Department of Radiology, Baoshan Hospital of Traditional Chinese Medicine and Western Medicine, Shanghai 201900, China

Received:2024-01-02 Revised:2024-05-24 Published:2024-11-15 Online:2024-11-12
Contact: △E-mail：19713115@qq.com

黄晓蕾, 葛婷婷, 赵俊松, 倪志华. 人参皂苷Rg1在IL-6诱导的大鼠神经元铁死亡中的作用[J]. 天津医药, 2024, 52(11): 1137-1140.

HUANG Xiaolei, GE Tingting, ZHAO Junsong, NI Zhihua. Study on the role of ginsenoside Rg1 in IL-6-induced neuronal ferroptosis in rats[J]. Tianjin Medical Journal, 2024, 52(11): 1137-1140.

摘要/Abstract

摘要：

目的探究人参皂苷Rg1（G-Rg1）通过调节Janus激活激酶（JAK）/信号传导及转录激活因子3（STAT3）信号通路对白细胞介素-6（IL-6）诱导的大鼠神经元损伤的保护作用和机制。方法大鼠海马神经元培养后，分为对照组（正常培养）、IL-6模型组（采用50 μg/L IL-6处理大鼠海马神经元18 h模拟脑内炎性环境）、G-Rg1低（10 μmol/L）剂量组、G-Rg1高（40 μmol/L）剂量组。培养48 h后，MTT法测定海马神经元存活率；分光光度法检测神经元总铁载量，并检测铁死亡标志物谷胱甘肽（GSH）、谷胱甘肽过氧化物酶4（GPX4）水平；qRT-PCR法检测海马神经元中膜铁转运蛋白1（FPN1）mRNA表达水平；蛋白免疫印迹法检测神经元JAK/STAT3信号通路相关蛋白表达。结果与对照组比较，IL-6模型组神经元存活率、GSH含量、GPX4含量、FPN1 mRNA表达水平均降低，总铁载量、p-JAK和p-STAT3蛋白表达水平升高（P<0.05）；与IL-6模型组比较，G-Rg1低、高剂量组神经元存活率、GSH含量、GPX4含量、FPN1 mRNA表达水平均升高，总铁载量、p-JAK和p-STAT3蛋白表达水平降低（P<0.05），且G-Rg1高剂量组上述各指标变化较G-Rg1低剂量组显著（P<0.05）。结论 G-Rg1缓解大鼠海马神经元铁死亡的作用机制可能与抑制IL-6/JAK/STAT3信号通路、上调FPN1表达、防止铁超载相关。

关键词: 人参皂苷Rg1, 神经元, 铁死亡, 白细胞介素6

Abstract:

Objective To investigate the protective effect and mechanism of ginsenoside Rg1 (G-Rg1) on interleukin-6 (IL-6)-induced neuronal injury in rats by regulating Janus activated kinase (JAK)/signal transducer and activator of transcription 3 (STAT3) signaling pathway. Methods After culture, rat hippocampal neurons were divided into the control group (normal culture), the IL-6 model group (50 μg/L IL-6 was used to treat rat hippocampal neurons for 18 h to simulate the inflammatory environment in brain), the G-Rg1 low dose (10 μmol/L) group and the G-Rg1 high dose (40 μmol/L) group. After 48 h of normal culture, the survival rate of hippocampal neurons was determined by MTT method. The total iron load of neurons was detected by spectrophotometry, and levels of ferroptosis markers glutathione (GSH) and glutathione peroxidase 4 (GPX4) were detected. The mRNA expression level of ferroportin 1 (FPN1) in hippocampal neurons was detected by qRT-PCR. The expression of proteins related to the neuronal JAK/STAT3 signaling pathway was detected by Western blot assay. Results Compared with the CON group, the neuronal survival rate, GSH content, GPX4 content and FPN1 mRNA expression level were decreased in the IL-6 model group, and the total iron load, p-JAK and p-STAT3 protein expression levels were increased (P<0.05). Compared with the IL-6 model group, the neuronal survival rate, GSH content, GPX4 content and FPN1 mRNA expression level were increased in the low-dose and high-dose G-Rg1 groups, and the total iron load, p-JAK and p-STAT3 protein expression levels were decreased (P<0.05). Changes of the above indicators were more significant in the high-dose G-Rg1 group than those in the low-dose G-Rg1 group (P<0.05). Conclusion The mechanism of G-Rg1 alleviating ferroptosis of hippocampal neurons in rats may be related to the inhibition of IL-6/JAK/STAT3 signaling pathway, up-regulation of FPN1 expression, and prevention of iron overload.

Key words: ginsenoside Rg1, neurons, ferroptosis, interleukin-6

中图分类号:

R285.5

图/表 4

参考文献 16

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基因名称	引物序列（5′→3′）	产物大小/bp
FPN1	上游：TTCCGCACTTTTCGAGATGG 下游：TACAGTCGAAGCCCAGGACTG	106
β-actin	上游：CTTTGCAGCTCCTTCGTTGC 下游：ACGATGGAGGGGAATACAGC	150

基因名称	引物序列（5′→3′）	产物大小/bp
FPN1	上游：TTCCGCACTTTTCGAGATGG 下游：TACAGTCGAAGCCCAGGACTG	106
β-actin	上游：CTTTGCAGCTCCTTCGTTGC 下游：ACGATGGAGGGGAATACAGC	150

组别		细胞存活率/%		总铁载量/（μmol/g）
对照组		99.99±0.27		1.76±0.04
IL-6模型组		81.16±1.16^a		5.29±0.13^a
G-Rg1低剂量组		84.37±1.09^ab		4.44±0.34^ab
G-Rg1高剂量组		92.52±0.83^abc		2.39±0.11^abc
F		259.334^＊		225.665^＊
组别	GSH/（μmol/g）		GPX4/（μmol/g）		FPN1 mRNA
对照组	82.82±0.72		32.21±0.41		1.00±0.06
IL-6模型组	39.94±1.03^a		11.32±0.20^a		0.23±0.03^a
G-Rg1低剂量组	50.97±1.48^ab		17.10±0.58^ab		0.47±0.04^ab
G-Rg1高剂量组	74.47±3.58^abc		28.19±3.46^abc		0.76±0.03^abc
F	288.715^＊		89.799^＊		187.197^＊

组别		细胞存活率/%		总铁载量/（μmol/g）
对照组		99.99±0.27		1.76±0.04
IL-6模型组		81.16±1.16^a		5.29±0.13^a
G-Rg1低剂量组		84.37±1.09^ab		4.44±0.34^ab
G-Rg1高剂量组		92.52±0.83^abc		2.39±0.11^abc
F		259.334^＊		225.665^＊
组别	GSH/（μmol/g）		GPX4/（μmol/g）		FPN1 mRNA
对照组	82.82±0.72		32.21±0.41		1.00±0.06
IL-6模型组	39.94±1.03^a		11.32±0.20^a		0.23±0.03^a
G-Rg1低剂量组	50.97±1.48^ab		17.10±0.58^ab		0.47±0.04^ab
G-Rg1高剂量组	74.47±3.58^abc		28.19±3.46^abc		0.76±0.03^abc
F	288.715^＊		89.799^＊		187.197^＊

组别	JAK	p-JAK	STAT3	p-STAT3
对照组	0.77±0.01	0.10±0.01	0.89±0.10	0.09±0.01
IL-6模型组	0.80±0.01^a	0.68±0.04^a	0.95±0.13^a	0.74±0.02^a
G-Rg1低剂量组	0.84±0.01^ab	0.56±0.01^ab	0.96±0.01^a	0.35±0.00^ab
G-Rg1高剂量组	0.68±0.02^abc	0.23±0.01^abc	0.92±0.01^abc	0.17±0.01^abc
F	174.685^＊	4 861.146^＊	37.523^＊	2 553.319^＊

人参皂苷Rg1在IL-6诱导的大鼠神经元铁死亡中的作用

Study on the role of ginsenoside Rg1 in IL-6-induced neuronal ferroptosis in rats

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