丹参酮ⅡA减轻高糖诱导的小鼠足细胞系PMC-5凋亡和氧化应激反应

doi:10.16352/j.issn.1001-6325.2023.02.277

基础医学与临床 ›› 2023, Vol. 43 ›› Issue (2): 277-282.doi: 10.16352/j.issn.1001-6325.2023.02.277

丹参酮ⅡA减轻高糖诱导的小鼠足细胞系PMC-5凋亡和氧化应激反应

张梦瑶¹, 牛姝¹, 蔡静¹, 张立香², 赵志刚^1*

1.石家庄市人民医院内分泌二科,河北石家庄 050000;
2.河北医科大学附属第二医院心内科,河北石家庄 050000

收稿日期:2021-12-17 修回日期:2022-07-03 出版日期:2023-02-05 发布日期:2023-02-02
通讯作者: ^*cen25m@163.com
基金资助:
2019年河北省医学科学研究重点课题(20190161)

Tanshinone ⅡA attenuates high glucose-induced apoptosis and oxidative stress in mouse podocyte line PMC-5

ZHANG Mengyao¹, NIU Shu¹, CAI Jing¹, ZHANG Lixiang², ZHAO Zhigang^1*

1. The Second Department of Endocrinology, Shijiazhuang People's Hospital, Shijiazhuang 050000;
2. Department of Cardiology, the Second Affiliated Hospital of Hebei Medical University, Shijiazhuang 050000,China

Received:2021-12-17 Revised:2022-07-03 Online:2023-02-05 Published:2023-02-02
Contact: ^*cen25m@163.com

摘要/Abstract

摘要： 目的研究丹参酮ⅡA(Tan ⅡA)是否可以减轻高糖(HG)诱导的足细胞凋亡和氧化应激。方法 CCK-8法筛选合适的Tan ⅡA干预浓度。MPC-5细胞依次分为:NC组(5.5 mmol/L D-葡萄糖)、MA组(5.5 mmol/L D-葡萄糖和22.5 mmol/L甘露醇)、HG组(25 mmol/L D-葡萄糖)、HG+Tan ⅡA组(25 mmol/L D-葡萄糖和10 μmol/L Tan ⅡA)和HG+Tan ⅡA+SIRT1抑制剂(Sirtinol)组(25 mmol/L D-葡萄糖、10 μmol/L Tan ⅡA和20 μmol/L Sirtinol)。微板法、WST-1法和可见光法测定氧化应激标志物丙二醛(MDA)、超氧化物歧化酶(SOD)、过氧化氢酶(CAT)活性;流式细胞术测定细胞凋亡;Western blot评估凋亡相关蛋白和沉默信息调节蛋白1(SIRT1)/内皮型一氧化氮合酶(eNOS)通路蛋白的表达。结果 Tan ⅡA提高了HG诱导的MPC-5细胞活力(P＜0.05)。与MA组相比,HG组细胞凋亡水平升高,细胞中B淋巴细胞瘤-2基因(Bcl-2)、磷酸化SIRT1(p-SIRT1)和磷酸化eNOS(p-eNOS)表达以及SOD和CAT活性降低,Bcl-2相关X蛋白(Bax)和裂解的caspase-3(cleaved caspase-3)表达及细胞中MDA含量增高(P＜0.05)。与HG组相比,Tan ⅡA组细胞凋亡水平降低,细胞中Bcl-2、p-SIRT1和p-eNOS表达以及SOD和CAT活性升高,Bax和cleaved caspase-3表达及MDA含量降低(P＜0.05)。SIRT1抑制剂Sirtinol可减轻Tan ⅡA对HG诱导的足细胞凋亡和氧化应激的抑制作用(P＜0.05)。结论 Tan ⅡA可能通过激活SIRT1/eNOS通路减轻HG诱导的足细胞系PMC-5凋亡和氧化应激反应。

关键词: 丹参酮ⅡA, 足细胞, 氧化应激, 细胞凋亡, 高糖

Abstract: Objective To explore potential mechanisms involved in the reduction of podocyte apoptosis and oxidative stress induced by high glucose (HG) by tanshinone ⅡA (Tan ⅡA). Methods CCK-8 method was used to screen the appropriate interference concentration of Tan ⅡA. The MPC-5 cells were divided into NC group (5.5 mmol/L D-glucose), MA group(5.5 mmol/L D-glucose and 22.5 mmol/L mannitol), HG group(25 mmol/L D-glucose), HG+Tan ⅡA group(25 mmol/L D-glucose and 10 μmol/L Tan ⅡA), and HG+Tan ⅡA+SIRT1 inhibitors(sirtinol) group (25 mmol/L D-glucose, 10 μmol/L Tan ⅡA and 20 μmol/L sirtinol). Determina- tion of oxidative stress markers malondialdehyde(MDA), superoxide dismutase (SOD) and catalase (CAT) were made by microplate method, WST-1 method and visible light method. Flow cytometry was used to measure cell apoptosis. Western blot was used to evaluate the expression of apoptosis-related proteins and silent information regulator 1 (SIRT1)/endothelial nitric oxide synthase (eNOS) pathway proteins. Results Tan ⅡA improved the viability of MPC-5 cells induced by HG (P＜0.05). Compared with the MA group, the level of cell apoptosis in the HG group increased, the expression of B-cell lymphoma-2 gene (Bcl-2), phosphorylated SIRT1 (p-SIRT1) and phosphorylated eNOS(p-eNOS) in the cells, and the activity of SOD and of CAT were reduced, the expression of Bcl-2-associated X protein (Bax) and cleaved caspase-3, and the content of MDA in cells were increased(P＜0.05). Compared with the HG group, the level of cell apoptosis in the Tan ⅡA group reduced, the expressions of Bcl-2, p-SIRT1 and p-eNOS in the cells, and the activity of SOD and CAT were increased, the expression of Bax and cleaved caspase-3, and the content of MDA in cells were reduced(P＜0.05). The SIRT1 inhibitor sirtinol attenuated the inhibitory effect of Tan ⅡA on HG-induced podocyte apoptosis and oxidative stress (P＜0.05). Conclusions Tan ⅡA may reduce HG-induced apoptosis and oxidative stress in podocytes with a potential mechanism of activating the SIRT1/eNOS pathway.

Key words: tanshinone ⅡA, podocytes, oxidative stress, apoptosis, high glucose

中图分类号:

R587.2

张梦瑶, 牛姝, 蔡静, 张立香, 赵志刚. 丹参酮ⅡA减轻高糖诱导的小鼠足细胞系PMC-5凋亡和氧化应激反应[J]. 基础医学与临床, 2023, 43(2): 277-282.

ZHANG Mengyao, NIU Shu, CAI Jing, ZHANG Lixiang, ZHAO Zhigang. Tanshinone ⅡA attenuates high glucose-induced apoptosis and oxidative stress in mouse podocyte line PMC-5[J]. Basic & Clinical Medicine, 2023, 43(2): 277-282.

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丹参酮ⅡA减轻高糖诱导的小鼠足细胞系PMC-5凋亡和氧化应激反应

Tanshinone ⅡA attenuates high glucose-induced apoptosis and oxidative stress in mouse podocyte line PMC-5

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