Protective effects of two novel nitronyl nitroxide radicals on heart failure induced by hypobaric hypoxia
Protective effects of two novel nitronyl nitroxide radicals on heart failure induced by hypobaric hypoxia
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两种新型硝酰基氮氧自由基对低压缺氧心力衰竭的保护作用
DOI：
10.1016/j.lfs.2019.05.037
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发表时间：
2020-05-01
期刊：
影响因子：
6.1
通讯作者：
Wang, Haibo
中科院分区：
文献类型：
--
作者：
Jing, Linlin;Shao, Jin;Wang, Haibo
目的：低压缺氧(HH)与氧化应激有关，损害心脏功能。我们合成了一种新型的硝基氮氧自由基--HPN衍生物(HEPN)，并研究了HEPN和HPN对HH所致小鼠心脏损伤的保护作用及其可能的作用机制。测定心功能。测定血清AST、CK、LDH和cTnI。测定心肌组织氧化酶活性、超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、谷胱甘肽过氧化物酶(GSH-Px)、活性氧(ROS)和丙二醛(MDA)。测定ATP含量、Na+/K+-ATPase和Ca2+/Mg2+-ATPase活性。检测HIF-1、VEGF、Nrf2、HO-1、Bax、Bcl2、Caspase-3的表达。主要结果：HEPN或HPN可显著降低小鼠血清中生化标志物AST、CK、LDH和cTnI的活性。提高小鼠心脏组织中超氧化物歧化酶、过氧化氢酶、谷胱甘肽过氧化物酶活性，降低ROS、丙二醛水平。HEPN和HPN可增加Nrf2和OH-1的表达。它们可以维持ATPase的活性。HPN或HEPN组与HH组比较，Bax、Caspase-3表达及Bax/Bcl2比值明显下调，Bcl2表达上调。它们可能通过清除自由基来减轻HH诱导的氧化应激。意义：本研究表明，硝基氮氧自由基HEPN和HPN可能是治疗HH所致心功能不全的潜在治疗药物。
Aims: Hypobaric hypoxia (HH), linked to oxidative stress, impairs cardiac function. We synthesized a novel nitronyl nitroxide radical, an HPN derivative (HEPN) and investigated the protective effects of HEPN and HPN against HH-induced heart injury in mice and the underlying mechanisms of action.Main methods: Mice were administered with HPN (200 mg/kg) or HEPN (200 mg/kg) 30 min before exposed to HH. The cardiac function was measured. Serum AST, CK, LDH and cTnI were estimated. Heart tissue oxidase activity, SOD, CAT, GSH-Px, ROS and MDA were estimated. ATP content, Na+/K+-ATPase and Ca2+/Mg2+-ATPase activity was measured. The expression of HIF-1, VEGF, Nrf2, HO-1, Bax, Bcl-2, Caspase-3 was estimated.Key findings: Results showed that pretreatment with HEPN or HPN led to a dramatic decrease in the activity of biochemical markers AST, CK, LDH and cTnI in murine serum. They increased the activity of SOD, CAT and GSH-Px and reduced the level of ROS and MDA in the hearts of mice. HEPN and HPN could increase the expression of Nrf2 and OH-1. They could maintain the ATPase activity. The Bax and Caspase-3 expression as well as the ratio of Bax/Bcl-2 were significantly downregulated and the Bcl-2 expression was upregulated by HPN or HEPN compared to the HH group. They may attenuate the HH-induced oxidant stress via free radical scavenging activity.Significance: The present study showed that the nitronyl nitroxide radical HEPN and HPN may be potential therapeutic agents for treatment of HH-induced cardiac dysfunction.