山茱萸总苷抑制高糖诱导的人肾小管上皮细胞系HK-2凋亡和氧化损伤

doi:10.16352/j.issn.1001-6325.2024.12.1644

基础医学与临床 ›› 2024, Vol. 44 ›› Issue (12): 1644-1650.doi: 10.16352/j.issn.1001-6325.2024.12.1644

山茱萸总苷抑制高糖诱导的人肾小管上皮细胞系HK-2凋亡和氧化损伤

张晓东¹, 李文冬¹, 陈景荷², 张艳琴^1*

宝鸡市人民医院 1.肾病内科;
2.重症医学科,陕西宝鸡 721000

收稿日期:2024-03-15 修回日期:2024-07-08 出版日期:2024-12-05 发布日期:2024-11-26
通讯作者: ^*594656517@qq.com
基金资助:
陕西省自然科学基础研究计划(2023-JC-YB-644)

Total cornus officinalis glycosides inhibit high glucose-induced cell apoptosis and oxidative damage of human renal tubular epithelial cell line HK-2

ZHANG Xiaodong¹, LI Wendong¹, CHEN Jinghe², ZHANG Yanqin^1*

1. Department of Nephrology;
2. Department of Critical Care Medicine, Baoji People's Hospital, Baoji 721000, China

Received:2024-03-15 Revised:2024-07-08 Online:2024-12-05 Published:2024-11-26
Contact: ^*594656517@qq.com

摘要/Abstract

摘要： 目的探究山茱萸总苷(COG)调节E2相关因子2(Nrf2)/血红素加氧酶1(HO-1)通路对高糖诱导的人肾小管上皮细胞系HK-2的凋亡和氧化损伤的影响。方法将人肾小管上皮细胞系HK-2分为对照组(control,5.5 mmol/L)、模型组(HG,30 mmol/L)、山茱萸总苷低、中和高剂量组(L-COG、M-COG、H-COG),加入Nrf2通路抑制剂后,HK-2细胞分为H-COG组、ML385组。CCK8法检测细胞活性,流式细胞术检测细胞凋亡,Western blot法检测Bcl-2相关X蛋白(Bax)、B细胞淋巴瘤/白血病-2(Bcl-2)、活化的胱天蛋白酶(cleaved-caspase3)、Nrf2/HO-1通路蛋白表达,DCFH-DA法检测活性氧(ROS)含量,ELISA法检测谷胱甘肽过氧化物酶(GSH-Px)活性、超氧化物歧化酶(SOD)活性、白介素-6(IL-6)及肿瘤坏死因子α(TNF-α)含量。结果与对照组比较,模型组细胞活性、Bcl-2蛋白表达、GSH-Px及SOD活性明显降低,凋亡率、Bax、Nrf2、HO-1及cleaved-caspase3蛋白表达、ROS、IL-6、TNF-α含量明显增加(P＜0.05);与模型组比较,L-COG、M-COG、H-COG组细胞活性、Bcl-2蛋白表达、GSH-Px、SOD活性明显增加,凋亡率、Bax、Nrf2、HO-1及cleaved-caspase3蛋白表达、ROS、IL-6、TNF-α含量明显降低(P＜0.05)。与H-COG组比较,ML385组细胞活性、Bcl-2蛋白表达、GSH-Px活性、SOD活性明显增加,凋亡率、Bax及cleaved-caspase3蛋白表达、ROS、IL-6、TNF-α含量明显降低(P＜0.05)。结论山茱萸总苷可能是通过抑制Nrf2/HO-1通路减轻高糖诱导的肾小管上皮细胞氧化应激和炎性反应,进而减轻细胞凋亡。

关键词: 山茱萸总苷, 高糖, 肾小管上皮细胞系, 凋亡, 氧化应激

Abstract: Objective To investigate the effect of cornus officinalis glycosides on apoptosis and oxidative damage of human renal tubular epithelial cells line induced by high glucose by regulating E2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway. Methods Human renal tubule epithelial cell line HK-2 was divided into control group (control, 5.5 mmol/L glucose), model group (HG, 30 mmol/L glucose), and total cornus officinalis glycosides groups with low, medium and high dose (L-COG, M-COG, H-COG). After Nrf2 pathway inhibitors were added, HK-2 cells were divided into H-COG group and ML385 group. CCK8 method was used to detect cell activity. Apoptosis was detected by flow cytometry. The expressions of Bcl-2 associated X protein (Bax), B-cell lymphoma/leukemia 2 (Bcl-2), activated caspase3 (cleaved caspase3), Nrf2/HO-1 pathway protein were detected by Western blot. Reactive oxygen species (ROS) content was detected by DCFH-DA, glutathione peroxidase (GSH-Px) activity, superoxide dismutase (SOD) activity, interleukin-6 (IL-6) content and tumor necrosis factor α (TNF-α) content were detected by ELISA. Results Compared with control group, the cell activity, Bcl-2 protein expression, GSH-Px and SOD activity in model group were significantly decreased, and the apoptosis rate, Bax, Nrf2, HO-1 and cleaved caspase3 protein expression, ROS, IL-6 and TNF-α content were significantly increased (P＜0.05). Compared with model group, the cell activity, Bcl-2 protein expression, GSH-Px and SOD activity of L-COG, M-COG, and H-COG were significantly increased. Apoptosis rate, Bax, Nrf2, HO-1, cleave-caspase3 protein expression, ROS, IL-6, TNF-α content were significantly decreased (P＜0.05). Compared with H-COG, the cell activity, Bcl-2 protein expression, GSH-Px and SOD activity in ML385 group were significantly increased. The apoptosis rate, Bax and cleaved caspase3 protein expression, ROS, IL-6, TNF-α content were significantly decreased (P＜0.05). Conclusions The total cornus officinis glucoside may reduce the oxidative stress and inflammatory response of renal tubular epithelial cells induced by high glucose through inhibiting Nrf2/HO-1 pathway and then reduce cell apoptosis.

Key words: total cornus officinalis glycosides, high glucose, renal tubular epithelial cell line, apoptosis, oxidative stress

中图分类号:

R285

张晓东, 李文冬, 陈景荷, 张艳琴. 山茱萸总苷抑制高糖诱导的人肾小管上皮细胞系HK-2凋亡和氧化损伤[J]. 基础医学与临床, 2024, 44(12): 1644-1650.

ZHANG Xiaodong, LI Wendong, CHEN Jinghe, ZHANG Yanqin. Total cornus officinalis glycosides inhibit high glucose-induced cell apoptosis and oxidative damage of human renal tubular epithelial cell line HK-2[J]. Basic & Clinical Medicine, 2024, 44(12): 1644-1650.

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山茱萸总苷抑制高糖诱导的人肾小管上皮细胞系HK-2凋亡和氧化损伤

Total cornus officinalis glycosides inhibit high glucose-induced cell apoptosis and oxidative damage of human renal tubular epithelial cell line HK-2

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