目的 研究氮氧自由基(nitronyl nitroxide)对高原缺氧小鼠心肌组织缺氧和凋亡蛋白的影响。方法 将48只小鼠随机分为正常对照组、缺氧模型组、乙酰唑胺组和氮氧自由基组,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,测定心肌组织中乳酸(LD)含量和乳酸脱氢酶(LDH)活性,Western blotting检测缺氧诱导因子-1α、血管内皮生长因子、caspase-3、Bcl-2和Bax蛋白的表达水平。结果 与正常对照组相比,缺氧模型组中乳酸含量和乳酸脱氢酶活性显著增加,缺氧诱导因子-1α、血管内皮生长因子、caspase-3和Bax蛋白表达增强,Bcl-2蛋白的表达和Bc1-2/Bax比值降低。经氮氧自由基预处理后能够显著降低高原缺氧小鼠心肌组织中乳酸含量和乳酸脱氢酶活性,降低缺氧诱导因子-1α、血管内皮生长因子、caspase-3和Bax蛋白表达,提高Bcl-2的蛋白表达和Bc1-2/Bax比值。结论 氮氧自由基对高原缺氧诱导的心肌组织损伤具有保护作用,该作用可能其与改善能量代谢、降低机体氧化应激及抑制心肌细胞凋亡等作用有关。
Abstract
OBJECTIVE To investigate the effects of nitronyl nitroxide(HPN)on the myocardial hypoxia- and the expression of apoptosis-associated proteins in hypobaric hypoxia condition mice. METHODS Sixty BALB/c mice were divided into normal control group,hypoxia model group,acetazolamide group and HPN group randomly. After single intraperitoneal injection of HPN for 30 min,the mice were exposed to a simulated high altitude of 8 000 m for 12 h. After hypoxic exposure,mice were sacrificed and the content of lactate(LD) and lactate dehydrogenase(LDH) activity in heart were determined. HIF-1,VEGF,caspase-3,Bax and Bcl-2 were detected by immunohistochemistry. RESULTS Compared with normal control group,the LD level and LDH activity in hypoxia model group increased significantly. In addition,the expression of HIF-1α,VEGF,caspase-3 and Bax were increased,Bcl-2 and Bc1-2/Bax ratio was decreased. Pre-treated with HNP the LD level and LDH activity,the expression of HIF-1α,VEGF,caspase-3 and Bax were decreased effectively,the expression of Bcl-2 and Bc1-2/Bax ratio was increased. CONCLUSION HPN has protective effect on heart injury induced by hypobaric hypoxia in mice. Its mechanism may be related to the amelioration of energy metabolism,alleviation of oxidative stress as well as inhibition of myocardial apoptosis.
关键词
氮氧自由基 /
低压低氧 /
缺氧诱导因子 /
凋亡
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Key words
nitronyl nitroxide /
hypobaric hypoxia /
hypoxia inducible factor /
apoptosis
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中图分类号：
R965.1
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参考文献
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脚注
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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(CLZ12JA04);甘肃省自然科学基金(1308RJYA06);中国博士后科学基金(2012M521926)
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