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过氧化物酶体增殖物激活受体6过表达调节阿霉素诱导的大鼠心肌损伤、氧化应激和免疫反应。

Peroxiredoxin 6 overexpression regulates adriamycin-induced myocardial injury, oxidative stress and immune response in rats.

作者信息

Guo Jianshu, Cao Weiping, Chen Chi, Chen Xiaohan

机构信息

Department of Geriatric Medicine, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science & Technology, Chengdu, China.

Department of Cardiology, People's Hospital of Leshan, Leshan, China.

出版信息

Ann Transl Med. 2020 Oct;8(20):1320. doi: 10.21037/atm-20-6598.

Abstract

BACKGROUND

Adriamycin is an anthracycline drug used to treat a variety of tumors. Adriamycin has a much stronger affinity for myocardial tissue than other body tissues. Cancer patients treated with adriamycin are prone to toxic damage to heart tissue. Peroxiredoxin 6 (PRDX6) is a novel antioxidant enzyme in metabolic diseases, the aim of this study was to investigate the role of PRDX6 in myocardial injury.

METHODS

Sixty male specific-pathogen-free Wistar rats were enrolled and divided equally into the control group (control), the Adriamycin group, the Adriamycin + empty vector lentivirus (Adriamycin + LV) group, and the Adriamycin + Peroxiredoxin 6 overexpression (Adriamycin + PRDX6) group. Western blot, reverse transcription-polymerase chain reaction (PCR), enzyme-linked immunosorbent assay, hematoxylin and eosin staining (HE) and immunohistochemistry were used in this research.

RESULTS

The myocardial tissues of the Adriamycin group had significantly lower expression levels of PRDX6 and PRDX6 mRNA than those of the control group, and the myocardial tissues of the Adriamycin + PRDX6 rats had significantly higher expression levels of PRDX6 and PRDX6 mRNA than those of the Adriamycin + LV group. Serum creatine kinase isoenzyme (CK-MB), myoglobin (Mb), cardiac troponin I (cTnI), myocardial injury, positive rate of caspase-3, B-cell lymphoma 2 (Bcl-2)/Bcl-2-associated X protein (Bax) levels, malondialdehyde (MDA), lactate dehydrogenase (LDH), IL-1β, IL-6, inducible nitric oxide synthase (iNOS), and IL-4 proteins in the adriamycin-induced rats were significantly higher than those in the control group, while superoxide dismutase (SOD) activity was significantly lower than that in the control group. PRDX6 overexpression reversed the above results.

CONCLUSIONS

PRDX6 overexpression can alleviate adriamycin-induced myocardial injury in rats, which may be related to oxidative stress regulation and the levels of inflammatory factors.

摘要

背景

阿霉素是一种用于治疗多种肿瘤的蒽环类药物。阿霉素对心肌组织的亲和力比其他身体组织强得多。接受阿霉素治疗的癌症患者容易出现心脏组织的毒性损伤。过氧化物酶体增殖物激活受体6(PRDX6)是代谢性疾病中的一种新型抗氧化酶,本研究旨在探讨PRDX6在心肌损伤中的作用。

方法

选取60只雄性无特定病原体的Wistar大鼠,将其平均分为对照组、阿霉素组、阿霉素+空载体慢病毒组(阿霉素+LV)和阿霉素+过氧化物酶体增殖物激活受体6过表达组(阿霉素+PRDX6)。本研究采用蛋白质免疫印迹法、逆转录-聚合酶链反应(PCR)、酶联免疫吸附测定、苏木精-伊红染色(HE)和免疫组织化学法。

结果

阿霉素组心肌组织中PRDX6和PRDX6 mRNA的表达水平显著低于对照组,阿霉素+PRDX6大鼠心肌组织中PRDX6和PRDX6 mRNA的表达水平显著高于阿霉素+LV组。阿霉素诱导的大鼠血清肌酸激酶同工酶(CK-MB)、肌红蛋白(Mb)、心肌肌钙蛋白I(cTnI)、心肌损伤、半胱天冬酶-3阳性率、B细胞淋巴瘤2(Bcl-2)/Bcl-2相关X蛋白(Bax)水平、丙二醛(MDA)、乳酸脱氢酶(LDH)、白细胞介素-1β、白细胞介素-6、诱导型一氧化氮合酶(iNOS)和白细胞介素-4蛋白显著高于对照组,而超氧化物歧化酶(SOD)活性显著低于对照组。PRDX6过表达逆转了上述结果。

结论

PRDX6过表达可减轻阿霉素诱导的大鼠心肌损伤,这可能与氧化应激调节和炎症因子水平有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57ff/7661857/2f67bae06b03/atm-08-20-1320-f1.jpg

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