甘松乙酸乙酯部位改善低压和低氧诱导的心肌组织损伤作用及机制

Ethyl Acetate Extract Fraction of Nardostachys chinensis Ameliorates Hypobaric Hypoxia-induced Myocardial Injury via Inhibiting Oxidative Stress

目的:研究甘松乙酸乙酯部位(EFNC)改善低压、低氧诱导的心肌组织损伤的作用和机制。方法:36只小鼠随机分为对照组、低压低氧诱导模型组、芦丁(500 mg·kg^(-1))组和EFNC(500 mg·kg^(-1))组,每日给药1次。连续灌胃给药5 d后,将小鼠置于低压低氧实验动物舱中,升至海拔8000 m,12 h后迅速处死,检测各组小鼠血清中乳酸脱氢酶(LDH)、肌酸激酶(CK)和肌酸激酶同工酶(CK-MB)活性;检测心肌组织中过氧化氢(H2O2)、丙二醛(MDA)、谷胱甘肽(GSH)水平以及超氧化物歧化酶(SOD)、过氧化物酶(CAT)和谷胱甘肽过氧化物酶(GSH-Px)活性;蛋白质免疫印迹法(Western blotting)检测心肌组织中核转录因子E2相关因子2(Nrf2)和血红素加氧酶1(HO-1)蛋白表达水平。结果:与对照组比较,模型组小鼠血清中LDH、CK和CK-MB活性显著升高,心肌组织中H2O2和MDA水平显著升高,GSH水平和SOD、CAT、GSH-Px活性显著降低,Nrf2和HO-1蛋白表达水平升高。经EFNC预处理后能够显著降低高原缺氧小鼠血清中LDH、CK和CK-MB活性及心肌组织中H2O2和MDA水平,提高心肌组织中抗氧化酶的活性和GSH水平,升高Nrf2和HO-1蛋白表达水平。结论:EFNC对低压低氧诱导的心肌组织损伤具有保护作用,该作用与清除自由基、激活Nrf2/HO-1信号通路、降低心肌组织氧化应激有关。

Objective:To assess whether ethyl acetate extract fraction of Nardostachys chinensis(EFNC)alleviates myocardial injury induced by hypobaric hypoxia(HH)via its anti-oxidative effects.Methods:36 male BALB/c mice were randomly assigned to four groups:control group,model group,rutin group and EFNC group.After given drug(500 mg·kg^(-1)·d^(-1))through gavage for five days,the mice were exposed to HH equivalent to 8000 m for 12 h.The mice were subsequently sacrificed and the blood and heart samples were collected for analysis.The serum biomarkers of cardiac function[lactate dehydrogenase(LDH),creatine kinase(CK)and creatine kinase-MB(CK-MB)]were assayed.The level of hydrogen peroxide(H2O2),malondialdehyde(MDA)and glutathione(GSH)as well as the activity of antioxidant enzyme were determined.The expression of nuclear factor erythroid 2-related factor 2(Nrf2)and heme oxygenase-1(HO-1)were detected by Western blotting.Results:Compared with control group,HH significantly increased LDH,CK and CK-MB levels in serum and the content of H2O2 and MDA in heart tissue,markedly decreased the level of GSH and the activity of superoxide dismutase(SOD),glutathione peroxidase(GSH-Px)and catalase(CAT),as well as unregulated the expression of Nrf2 and HO-1 in heart tissue.Prior administration of EFNC decreased LDH,CK and CK-MB levels in serum and reduced the level of H2O2 and MDA,elevated the GSH content and activity of SOD,CAT and GSH-Px in heart tissue.In addition,EFNC could further increase the expression of Nrf2 and HO-1.Conclusion:EFNC exerted its protective effect on myocardial injury induced by HH in mice likely through scavenging free radical,activating of Nrf2/HO-1 pathway and suppressing oxidative stress in heart tissue.