The irreversible loss of cardiomyocytes is mainly the result of ischemic/reperfusion (I/R) myocardial injury, leading to persistent heart dysfunction and heart failure. It has been reported that Lycium barbarum polysaccharide (LBP) has protective effects on cardiomyocytes, but the specific mechanism is still not completely understood. The present study examined the protective role of LBP in myocardial I/R injury. Rats were subjected to myocardial I/R injury and LBP treatment. Moreover, rat myocardial H9C2 cells exposed to hypoxia/reoxygenation (H/R) were used to simulate cardiac injury during myocardial I/R process and were exposed to LBP, rapamycin (an autophagy activator) or nuclear factor‑erythroid factor 2‑related factor 2 (Nrf2) transfection. Morphological examination, histopathological examination and echocardiography were used to determine the cardiac injury after I/R injury. Cell viability and apoptosis were determined via MTT and flow cytometry assays, respectively. The levels of lactate dehydrogenase (LDH), creatine kinase (CK), cardiac troponin T (cTnT), IL‑1β, IL‑6, TNF‑α, malondialdehyde (MDA) and superoxidase dismutase (SOD) in rat serum, hearts and/or cells were assessed using ELISAs. The expression levels of Beclin 1, LC3II/LC3I, P62 and Nrf2 were analyzed via reverse transcription‑quantitative PCR and western blotting. The results demonstrated that LBP improved heart function and repaired cardiomyocyte damage in I/R model rats, as well as reduced the production of cTnT, CK, LDH, IL‑1β, IL‑6 and TNF‑α. The in vitro study results indicated that LBP increased cell viability, the apoptosis rate, and the levels of SOD and P62, as well as reduced the levels of LDH, CK, IL‑1β, IL‑6, TNF‑α, MDA, Beclin 1 and LC3‑II/LC3‑I in H/R‑injured H9C2 cells. Moreover, LBP promoted Nrf2 nuclear translocation, but decreased Nrf2 expression in the cytoplasm. Rapamycin exacerbated the aforementioned effects in H/R injured H9C2 cells, and partially reversed LBP‑induced effects. Overexpressing Nrf2 counteracted I/R‑induced effects and partially resisted rapamycin‑induced effects. These findings demonstrated that LBP exhibited a cardiac protective effect on the ischemic myocardium of rats after reperfusion and attenuated myocardial I/R injury via autophagy inhibition‑induced Nrf2 activation.

中文翻译：

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枸杞多糖通过自噬抑制激活 Nrf2 保护大鼠和心肌细胞免受缺血/再灌注损伤。

心肌细胞的不可逆损失主要是缺血/再灌注（I/R）心肌损伤的结果，导致持续性心功能不全和心力衰竭。据报道，枸杞多糖（LBP）对心肌细胞有保护作用，但具体机制尚不完全清楚。本研究探讨了 LBP 在心肌 I/R 损伤中的保护作用。大鼠接受心肌 I/R 损伤和 LBP 治疗。此外，暴露于缺氧/复氧（H/R）的大鼠心肌H9C2细胞用于模拟心肌I/R过程中的心脏损伤，并暴露于LBP、雷帕霉素（一种自噬激活剂）或核因子-红细胞因子2相关因子2 (Nrf2) 转染。形态学检查、组织病理学检查和超声心动图用于确定I/R损伤后的心脏损伤。分别通过 MTT 和流式细胞术测定细胞活力和细胞凋亡。乳酸脱氢酶 (LDH)、肌酸激酶 (CK)、使用 ELISA 评估大鼠血清、心脏和/或细胞中的心肌肌钙蛋白 T (cTnT)、IL-1β、IL-6、TNF-α、丙二醛 (MDA) 和超氧化物酶歧化酶 (SOD)。通过逆转录定量 PCR 和蛋白质印迹分析 Beclin 1、LC3II/LC3I、P62 和 Nrf2 的表达水平。结果表明，LBP改善了I/R模型大鼠的心脏功能并修复了心肌细胞损伤，并减少了cTnT、CK、LDH、IL-1β、IL-6和TNF-α的产生。体外研究结果表明，LBP提高细胞活力、凋亡率、SOD和P62水平，降低LDH、CK、IL-1β、IL-6、TNF-α、MDA、Beclin水平。 H/R 损伤的 H9C2 细胞中的 1 和 LC3-II/LC3-I。此外，LBP 促进 Nrf2 核转位，但降低 Nrf2 在细胞质中的表达。雷帕霉素在 H/R 损伤的 H9C2 细胞中加剧了上述作用，并部分逆转了 LBP 诱导的作用。过表达 Nrf2 抵消了 I/R 诱导的效应并部分抵抗了雷帕霉素诱导的效应。这些发现表明，LBP 对再灌注后大鼠缺血心肌具有心脏保护作用，并通过自噬抑制诱导的 Nrf2 激活减轻心肌 I/R 损伤。