当归提取物对低压低氧致小鼠心肌组织损伤的保护作用

Protective Effect of Angelica Sinensis Extract against Myocardial Tissue Damage Caused by Hypobaric Hypoxia in Mice

目的考察当归提取物在体内的抗缺氧活性及其对低压低氧小鼠心肌组织的保护作用。方法将60只雄性小鼠分为6组,每组10只,即正常对照组、低压低氧组、阳性对照组(乙酰唑胺)和当归提取物低、中、高剂量组(100、200、400 mg·kg^(-1)),连续灌胃5 d,最后1次给药后,除正常对照组外,其余小鼠在模拟8000米海拔的低氧舱中暴露24 h,随后处死小鼠,取心肌组织,苏木精伊红染色观察小鼠心肌组织病理变化,测定心肌组织中活性氧自由基、丙二醛、过氧化氢、谷胱甘肽、超氧化物歧化酶和总抗氧化能力水平;测定心肌组织中肌酸激酶、乳酸脱氢酶、三磷酸腺苷、Na^(+)-K^(+)ATP酶、Ca^(2+)-Mg^(2+)ATP酶的活力;酶联免疫法测定心肌组织中肌酸激酶同工酶、天冬氨酸转氨酶的活性;蛋白印迹法检测心肌组织中缺氧诱导因子-1α,血管内皮生长因子、核因子E_(2)相关因子2、血红素加氧酶1蛋白的表达水平。结果与正常对照组比较,低压低氧组小鼠心肌组织中出现明显损伤,氧化应激指标显著升高,抗氧化能力显著降低,能量代谢出现障碍,缺氧蛋白表达上调,各指标数据均有显著性差异,说明低压低氧模型建立成功。与低压低氧组比较,当归提取物给药组小鼠心肌组织中损伤减轻,氧化应激指标降低,抗氧化能力提高,减轻能量代谢障碍,缺氧蛋白表达下调。结论当归提取物能够减轻氧化应激损伤,提高抗氧化活性,缓解能量代谢障碍,降低缺氧相关蛋白表达,从而减轻低压低氧诱发心肌组织损伤。

Objective To investigate the anti-hypoxic activity of Angelica sinensis extract in vivo and its protective effect on myocardial tissues of hypobaric hypoxic mice.Methods Sixty male mice were evenly divided into 6 groups:normal control group,hypobaric hypoxia group,positive control group(acetazolamide)and Angelica extract low,medium and high dose(100,200 and 400 mg·kg^(-1))groups.All the mice were administered by gavage for 5 d.After the last administration,all mice except the normal control group were exposed to a hypoxic chamber simulating a 8000 m altitude for 24 h before they were sacrificed and myocardial tissues were removed.HE staining was performed to observe the histopathological changes in the mice.The levels of reactive oxygen radicals,malondialdehyde,hydrogen peroxide,glutathione,superoxide dismutase,and total antioxidant capacity in myocardial tissues were measured,so were levels of creatine kinase,lactate dehydrogenase and the activities of adenosine triphosphate,Na^(+),K^(+)-ATPase,and Ca^(2+),Mg^(2+)-ATPase.The activities of creatine kinase isoenzymes and glutamic-oxalacetic transaminase were measured via enzyme-linked immunoassay while the expressions of hypoxia-inducible factor-1α,vascular endothelial growth factor,nuclear factor E_(2)-related factor 2,and heme oxygenase 1 protein in myocardial tissues were measured via protein blotting.Results Compared with the normal control group,mice in the hypobaric hypoxia group showed significant damage to myocardial tissues,significantly higher oxidative stress indexes,significantly lower antioxidant capacity,impaired energy metabolism,and upregu-lated hypoxic protein expressions.All the indexes were significantly different,so a workable hypobaric hypoxia model was established.Compared with the hypobaric hypoxia group,the Angelica extract administration group showed miti-gated damage to myocardial tissues,lowered oxidative stress indexes,improved antioxidant capacity,reduced impaired energy metabolism and down-regulated hypoxic protein expressions.Conclusion Angelica sinensis extract can reduce oxidative stress damage,increase antioxidant activity,alleviate impaired energy metabolism,and reduce hypoxia-relat-ed protein expressions,thereby mitigating hypobaric hypoxia-induced myocardial tissue damage.