介导炎症和氧化应激的新型自由基清除剂纳米粒抗电离辐射心脏损伤作用

    Novel free radical scavenger nanoparticles mediating inflammation and oxidative stress resists ionizing radiation induced cardiac injury

      摘要
    • 摘要:
      目的 研究一种新型自由基清除剂咪唑氮氧自由基纳米粒通过调控炎症及氧化应激对小鼠电离辐射后心脏损伤的防护作用及机制。
      方法  采用溶剂乳化法制备了咪唑氮氧自由基（C4-NIT）的纳米粒（NPs-C4-NIT），测定了NPs-C4-NIT纳米粒的包封率、载药量及纳米粒径；以雄性BALB/c小鼠为研究对象，考察了辐照后小鼠的存活率，测定小鼠血液生化指标，小鼠心脏组织中CAT、SOD、GSH-Px、MDA、LDH的水平，ELISA法测定小鼠心肌组织中炎性细胞因子水平，Western blot检测小鼠心肌组织中p53、Bcl-2、Bax、cleaved-caspase3、Nrf-2和HO-1蛋白的表达水平，HE染色法观察纳米粒对辐照后小鼠心肌组织的保护作用。
      结果  NPs-C4-NIT纳米粒在小鼠心肌组织中的循环代谢时间显著延长，明显提高了辐照后小鼠的存活率(P<0.05)，改善了辐照诱发的小鼠心肌组织病理损伤和心脏功能(P<0.01)，激活Nrf2和HO-1通路调控小鼠心肌组织中抗氧化酶的活力（P<0.01），降低脂质代谢产物的含量，显著降低促炎因子IL-1β和TNF-α的水平（P<0.01），增加抗炎因子IL-4的水平（P<0.01），并通过调节p53及相关细胞凋亡蛋白的表达抑制辐射后小鼠心肌组织的细胞凋亡（P<0.01）。
      结论  纳米粒NPs-C4-NIT对γ射线所致的小鼠心肌损伤具有明显的抑制作用，减轻氧化应激及炎症反应，抑制细胞凋亡，发挥抗电离辐射心脏防护作用。

       

      Abstract:
      AIM To investigate the protective effect of a novel nanoparticle prepared by a novel free radical scavenger, imidazole nitronyl nitroxide radical (NIT), on the myocardial tissue after ionizing radiation by regulating inflammation and oxidative stress, and its mechanism.
      METHODS Nanoparticles (NPs-C4-NIT) containing NIT (C4-NIT) were prepared using solvent emulsification method. The encapsulation efficiency, drug loading capacity and particle size of the nanoparticles were measured. Male BALB/c mice were used as the research subjects, the survival rate of mice after irradiation was investigated and the blood biochemical indicators and levels of CAT, SOD, GSH-Px, MDA and LDH in the mouse heart tissue were measured. ELISA method was used to measure the levels of inflammatory cytokines in the mouse cardiac tissue and Western blotting was used to detect the expression levels of p53, Bcl-2, Bax, cleaved-caspase3, Nrf-2 and HO-1 proteins in the mouse cardiac tissue. HE staining method was used to observe the protective effect on the mouse myocardial tissue.
      RESULTS The circulating metabolic time of NPs-C4-NIT nanoparticles in the mouse myocardial tissue was significantly prolonged, which significantly improved the survival rate of irradiated mice as well as the pathological damage (P<0.05) and cardiac functions induced by irradiation. The activity of antioxidant enzymes in the myocardial tissue increased and the content of lipid metabolites reduced. Meanwhile, NPs-C4-NIT significantly reduced the expression of p53 and Bax cleared caspase3 in the irradiated myocardial tissue (P<0.01) and increased the expression levels of Bcl-2, Nrf-2 and HO-1 proteins (P<0.01）. The pro-inflammatory factors IL-1β and TNF-α were significantly reduced (P<0.01) and the level of anti-inflammatory factor IL-4 was increased (P<0.01).
      CONCLUSION Nanoparticles NPs-C4-NIT have a significant inhibitory effect on the γ radiation induced myocardial oxidative damage in mice. NPs-C4-NIT can alleviate inflammatory reactions, inhibit cell apoptosis and exert anti ionizing radiation cardioprotective effects.

       

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