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[摘要]
目的 探讨藏紫菀总黄酮对高原缺氧小鼠抗氧化能力及细胞凋亡的影响。方法 采用常压密闭实验筛选藏紫菀总黄酮最佳抗缺氧剂量;40只小鼠随机分为对照组、模型组、乙酰唑胺(200 mg/kg)组和藏紫菀总黄酮(500 mg/kg)组,模拟海拔8000 m高原环境,减压缺氧12 h,测定小鼠脑组织中的过氧化氢酶(CAT)、谷胱甘肽过氧化物酶(GSH-Px)、还原型谷胱甘肽(GSH)和超氧化物歧化酶(SOD)活性,Western blotting法检测Nrf-2、SOD、Bcl-2和Bax蛋白表达。结果 常压密闭实验中,藏紫菀总黄酮500 mg/kg剂量组小鼠的存活时间最长,为最佳给药剂量;与对照组比较,缺氧后小鼠脑组织中SOD、CAT、GSH和GSH-Px活性均显著降低,Nrf-2蛋白表达显著升高,SOD蛋白表达和Bc1-2/Bax比值显著降低 (P<0.01);经藏紫菀总黄酮预处理后,小鼠脑组织中SOD、CAT、GSH和GSH-Px活性均显著升高,Nrf-2、SOD蛋白表达和Bcl-2/Bax比值显著升高(P<0.05、0.01)。结论 藏紫菀总黄酮提高高原缺氧小鼠脑组织抗氧化能力,降低细胞凋亡。
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[Abstract]
Objective To study the effects of total flavonoids from Aster souliei (ASF) on the expression of hypoxia-associated and apoptosis-associated proteins in brain of mice under hypobaric hypoxia condition. Methods The best dose of ASF to antihypoxia was determined by closed normobaric hypoxia experiment. Forty BALB/c mice were randomly divided into control group, model group, acetazolamide (200 mg/kg) group, and ASF (500 mg/kg) group. The mice were exposed to a simulated high altitude of 8 000 m for 12 h. After hypoxic exposure, mice were sacrificed and the activities of catalase (CAT), supersxide dismutase (SOD), glutathione (GSH), and reduced glutathione tablets (GSH-Px) in brain were determined. Nrf-2, SOD, Bax, and Bcl-2 were detected by Western blotting. Results Compared with control group, the CAT, SOD, GSH, and GSH-PX activity in model group significantly decreased. In addition, the expression of Nrf-2 increased, SOD and Bc1-2/Bax ratio decreased (P < 0.01). Prior administration of ASF effectively increased CAT, SOD, GSH, and GSH-Px activity as well as the expression of Nrf-2, SOD, and Bc1-2/Bax ratio(P < 0.05, 0.01). Conclusion ASF can improve the ability of anti-oxidant enzymes, alleviate oxidative stress as well as inhibit myocardial apoptosis of mice under hypobaric hypoxia condition.
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[基金项目]
全军医药卫生科研基金课题(CLZ11JA06);甘肃省自然科学基金(1107RJZA100)