Key Laboratory of Zoonosis of Liaoning Province, College of Animal Science & Veterinary Medicine, Shenyang Agricultural University, Shenyang 110866, China.
Fushun Modern Agriculture and Poverty Alleviation and Development Promotion Center, Fushun 113006, China.
Oxid Med Cell Longev. 2020 Mar 4;2020:7639109. doi: 10.1155/2020/7639109. eCollection 2020.
This study assessed the protective mechanism of astaxanthin (ASX) against ochratoxin A- (OTA-) induced cardiac injury in mice. Four groups of mice were established: control group (0.1 mL olive oil + 0.1 mL NaHCO), OTA group (0.1 mL OTA 5 mg/kg body weight), ASX group (0.1 mL ASX 100 mg/kg body weight), and ASX + OTA group (0.1 mL ASX 100 mg/kg body weight, 2 h later, 0.1 mL OTA 5 mg/kg body weight). The test period lasted for 27 days (7 days of dosing, 2 days of rest). Electrocardiogram, body weight, heart weight, tissue pathology, oxidative markers (malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH)), biochemical markers (creatine kinase (CK), creatine kinase isoenzyme (CK-MB), and lactate dehydrogenase (LDH)), electron microscopy, TUNEL, and Western blot tests were used to examine the effects of OTA on myocardial injury and ASX detoxification. The results showed that OTA exposure significantly decreased both body weight and heart weight. OTA induced a decrease in heart rate in mice and decreased tissue concentrations of SOD, CAT, and GSH, while increasing serum concentrations of cardiac enzymes (CK, CK-MB, and LDH) and tissue MDA. ASX improved heart rate, cardiac enzymes, and antioxidant levels in mice. The results of tissue pathology and TUNEL assay showed that ASX protects against OTA-induced myocardial injury. In addition, Western blot results showed that the OTA group upregulated Keap1, Bax, Caspase3, and Caspase9, while it downregulated Nrf2, HO-1, and Bcl-2 protein expression. ASX played a protective role by changing the expression of Keap1, Nrf2, HO-1, Bax, Bcl-2, Caspase3, and Caspase9 proteins. These results indicate that the protective mechanism of ASX on the myocardium works through the Keap1-Nrf2 signaling pathway and mitochondria-mediated apoptosis pathway. This study provides a molecular rationale for the mechanism underlying OTA-induced myocardial injury and the protective effect of ASX on the myocardium.
本研究评估了虾青素（ASX）对霉菌毒素 ochratoxin A（OTA）诱导的小鼠心脏损伤的保护机制。建立了四组小鼠：对照组（0.1 mL 橄榄油+0.1 mL NaHCO）、OTA 组（0.1 mL OTA 5 mg/kg 体重）、ASX 组（0.1 mL ASX 100 mg/kg 体重）和 ASX+OTA 组（0.1 mL ASX 100 mg/kg 体重，2 小时后，0.1 mL OTA 5 mg/kg 体重）。试验期为 27 天（给药 7 天，休息 2 天）。心电图、体重、心脏重量、组织病理学、氧化标志物（丙二醛（MDA）、超氧化物歧化酶（SOD）、过氧化氢酶（CAT）和谷胱甘肽（GSH））、生化标志物（肌酸激酶（CK）、肌酸激酶同工酶（CK-MB）和乳酸脱氢酶（LDH））、电子显微镜、TUNEL 和 Western blot 试验用于检测 OTA 对心肌损伤和 ASX 解毒的影响。结果表明，OTA 暴露显著降低了体重和心脏重量。OTA 诱导小鼠心率下降，组织 SOD、CAT 和 GSH 浓度降低，血清心脏酶（CK、CK-MB 和 LDH）和组织 MDA 浓度升高。ASX 提高了小鼠的心率、心脏酶和抗氧化水平。组织病理学和 TUNEL 检测结果表明，ASX 可预防 OTA 诱导的心肌损伤。此外，Western blot 结果表明，OTA 组上调 Keap1、Bax、Caspase3 和 Caspase9，而下调 Nrf2、HO-1 和 Bcl-2 蛋白表达。ASX 通过改变 Keap1、Nrf2、HO-1、Bax、Bcl-2、Caspase3 和 Caspase9 蛋白的表达发挥保护作用。这些结果表明，ASX 对心肌的保护机制通过 Keap1-Nrf2 信号通路和线粒体介导的细胞凋亡途径发挥作用。本研究为 OTA 诱导的心肌损伤机制和 ASX 对心肌的保护作用提供了分子基础。
