4-羟基-2,2,6,6-四甲基哌啶基-N-氧化物对高原缺氧小鼠心肌组织损伤的保护作用及机制研究

发布时间：2018-04-26 09:14

  本文选题：-羟基- + -四甲基哌啶基-N-氧化物　； 参考：《中国药学杂志》2017年18期

【摘要】：目的研究4-羟基-2,2,6,6-四甲基哌啶基-N-氧化物(tempol)对高原缺氧小鼠心肌组织的保护作用及机制。方法将110只小鼠随机分为正常对照组、缺氧模型组、乙酰唑胺组和tempol组,单次腹腔注射给药30 min后,在模拟海拔8 000 m环境停留12 h,眼眶取血后,测定血清中乳酸脱氢酶(LDH)和肌酸激酶(CK)活性,然后处死小鼠,检测心肌组织中过氧化氢(H_2O_2)和丙二醛(MDA)含量以及ATP酶和抗氧化酶的活性,蛋白印迹法检测缺氧诱导因子-1α(HIF-1α)、血管内皮生长因子(VEGF)、核因子E2相关因子2(Nrf2)和血红素氧合酶-1(HO-1)蛋白的表达水平。结果与正常对照组相比,缺氧模型组血清中CK和LDH的活性显著增加,心肌组织中H_2O_2和MDA含量显著升高,ATP酶和抗氧化酶的活性显著降低,HIF-1α、VEGF、Nrf2和HO-1蛋白表达增强。经tempol预处理后能够显著降低高原缺氧小鼠血清中CK和LDH的活性,减少心肌组织中H_2O_2和MDA含量,提高ATP酶和抗氧化酶的活性,降低HIF-1α、VEGF蛋白表达,显著提高Nrf2和HO-1蛋白表达。结论 Tempol对高原缺氧诱导的心肌组织损伤具有保护作用,该作用与改善能量代谢,清除自由基,激活Nrf2/HO-1信号途径,提高抗氧化酶活性,降低机体氧化应激有关。
[Abstract]:Objective to study the protective effect and mechanism of 4-hydroxy-2-dimethylidene 6-tetramethylpiperidine (6-tetramethylpiperidinyl) on myocardial tissue of mice exposed to hypoxia at high altitude. Methods 110 mice were randomly divided into three groups: normal control group, hypoxia model group, acetazolamide group and tempol group. After 30 min of single intraperitoneal injection, the mice stayed at a simulated altitude of 8 000 m for 12 hours. The activities of lactate dehydrogenase (LDH) and creatine kinase (CK) in serum were measured. Then the mice were killed. The contents of H _ 2O _ 2) and malondialdehyde (MDA) in myocardial tissue and the activities of ATP and antioxidant enzymes were measured. The expression levels of hypoxia inducible factor-1 伪 (HIF-1 伪), vascular endothelial growth factor (VEGFN), nuclear factor E2 related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) protein were detected by Western blot. Results compared with the normal control group, the activities of CK and LDH in serum of hypoxic model group were significantly increased, and the contents of H_2O_2 and MDA in myocardial tissue were significantly increased. The activities of ATPase and antioxidant enzymes were significantly decreased in hypoxic model group. The expression of HIF-1 伪 -VEGFNrf2 and HO-1 protein was significantly decreased in hypoxic model group. Pretreatment with tempol could significantly decrease the activities of CK and LDH in serum, decrease the contents of H_2O_2 and MDA in myocardium, increase the activities of ATP and antioxidant enzymes, decrease the expression of HIF-1 伪 -VEGF-protein, and increase the expression of Nrf2 and HO-1 protein. Conclusion Tempol has protective effect on myocardial tissue injury induced by hypoxia at high altitude, which is related to improving energy metabolism, scavenging free radicals, activating Nrf2/HO-1 signaling pathway, increasing antioxidant enzyme activity and reducing oxidative stress.
【作者单位】： 兰州总医院药剂科全军高原环境损伤防治重点实验室;
【基金】：国家自然科学基金资助项目(81202458) 全军医药科研“十二五”面上项目资助(CLZ12JA04) 甘肃省自然科学基金资助项目(1308RJYA06) 中国博士后科学基金资助项目(2012M521926)
【分类号】：R965
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本文编号：1805388