Sun Ning, Wang Hui, Wang Lin
Department of Geriatrics, Tianjin Medical University General Hospital, Tianjin Geriatrics Institute, Tianjin 300052, P.R. China.
Department of Geriatrics, The Second Hospital of Tianjin Medical University, Tianjin 300211, P.R. China.
Mol Med Rep. 2016 Sep;14(3):2764-70. doi: 10.3892/mmr.2016.5535. Epub 2016 Jul 20.
The present study aimed to investigate the protective effects of ghrelin against oxidative stress, inducible nitric oxide synthase (iNOS) and inflammation in a mouse model of myocardial ischemia/reperfusion injury (MIRI). In addition, the study aimed to determine its underlying mechanisms. A mouse model of MIRI was used in vivo, in order to ascertain the protective effects of ghrelin on MIRI. Commercial kits were used to measure the serum levels of creatine kinase (CK) and lactate dehydrogenase (LDH) in MIRI mice. Furthermore, Evan's Blue-triphenyltetrazolium chloride solution was used to analyze the protective effects of ghrelin against infarct size in MIRI mice. The underlying mechanisms were determined by measuring MIRI-induced tumor necrosis factor (TNF)‑α, interleukin (IL)‑6, superoxide dismutase (SOD), glutathione (GSH), GSH-peroxidase (GSH‑PX), malondialdehyde (MDA) and caspase‑3/caspase‑9 activities, and iNOS, high mobility group box 1 (HMGB1), Toll‑like receptor 4 (TLR4) and nuclear factor (NF)‑κB protein expression in MIRI mice. The results demonstrated that MIRI led to an increase in infarct size; CK, LDH, TNF‑α, IL‑6, MDA, caspase‑3 and caspase-9 serum levels; and iNOS protein expression. MIRI resulted in inhibition of SOD, FSH and GSH‑PX levels. Conversely, these alterations were significantly inhibited following treatment with ghrelin. In addition, the protective effects of ghrelin against MIRI suppressed HMGB1, TLR4 and NF‑κB protein expression in MIRI mice. The present study revealed that ghrelin exerted protective effects against oxidative stress, iNOS and inflammation in MIRI mice via the HMGB1/TLR4/NF-κB pathway.
本研究旨在探讨胃饥饿素对心肌缺血/再灌注损伤（MIRI）小鼠模型中氧化应激、诱导型一氧化氮合酶（iNOS）和炎症的保护作用。此外，该研究旨在确定其潜在机制。在体内使用MIRI小鼠模型，以确定胃饥饿素对MIRI的保护作用。使用商业试剂盒测量MIRI小鼠血清中的肌酸激酶（CK）和乳酸脱氢酶（LDH）水平。此外，使用伊文思蓝-氯化三苯基四氮唑溶液分析胃饥饿素对MIRI小鼠梗死面积的保护作用。通过测量MIRI诱导的肿瘤坏死因子（TNF）-α、白细胞介素（IL）-6、超氧化物歧化酶（SOD）、谷胱甘肽（GSH）、谷胱甘肽过氧化物酶（GSH-PX）、丙二醛（MDA）和半胱天冬酶-3/半胱天冬酶-9活性，以及MIRI小鼠中iNOS、高迁移率族蛋白B1（HMGB1）、Toll样受体4（TLR4）和核因子（NF）-κB蛋白表达来确定潜在机制。结果表明，MIRI导致梗死面积增加；CK、LDH、TNF-α、IL-6、MDA、半胱天冬酶-3和半胱天冬酶-9血清水平升高；以及iNOS蛋白表达增加。MIRI导致SOD、FSH和GSH-PX水平受到抑制。相反，用胃饥饿素治疗后，这些改变受到显著抑制。此外，胃饥饿素对MIRI的保护作用抑制了MIRI小鼠中HMGB1、TLR4和NF-κB蛋白表达。本研究表明，胃饥饿素通过HMGB1/TLR4/NF-κB途径对MIRI小鼠的氧化应激、iNOS和炎症发挥保护作用。
