藏紫菀总黄酮对模拟高原缺氧小鼠抗氧化能力及细胞凋亡的影响

Effects of total flavonoids from Aster souliei on hypoxia and apoptosis-ssociated proteins in brain of mice under hypobaric hypoxia condition

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。

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 Bc 1-2/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 Bcl-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.