黄芩素-7-甲醚对高原缺氧诱导小鼠心肌组织损伤的保护作用研究  

Protective Effect of Negletein on Hypobaric Hypoxia-induced Myocardial Tissue Damage in Mice

作　　者：邵瑾 杨颖[1,2] 何蕾 马慧萍 贾正平 景临林[2] SHAO Jin;YANG Ying;HE Lei;MA Hui-ping;JIA Zheng-ping;JING Lin-lin(College of Pharmacy,Lanzhou University,Lanzhou 730000,China;Department of Pharmacy,940 Hospital of PLA Joint Logistics Support Forces,Lanzhou 730050,China)

机构地区：[1]兰州大学药学院,兰州730000 [2]中国人民解放军联勤保障部队第九四〇医院药剂科,兰州730050

出　　处：《解放军医药杂志》2019年第6期1-5,共5页Medical & Pharmaceutical Journal of Chinese People’s Liberation Army

基　　金：国家自然科学基金项目(81872796,81202458);甘肃省自然科学基金(18JR3RA408,1308RJYA06);中国博士后科学基金(2012M521926)

摘　　要：目的探讨黄芩素-7-甲醚对高原缺氧诱导小鼠心肌组织损伤的保护作用。方法将40只雄性BALB/C小鼠随机分为正常对照组(注射用水灌胃)、缺氧模型组(注射用水灌胃)、芦丁组(500mg/kg灌胃)和黄芩素-7-甲醚组(500mg/kg灌胃),每组10只。除正常对照组外,其余3组均置于模拟高原环境8000m条件下缺氧12h。然后所有小鼠均眼眶采血,测定血清乳酸脱氢酶(LDH)和肌酸激酶(CK)活性;最后处死小鼠取心肌组织,检测过氧化氢(H2O2)和丙二醛(MDA)含量,测定超氧化物歧化酶(SOD)、过氧化氢酶(CAT)和谷胱甘肽过氧化物酶(GSH-Px)的活性,同时检测核因子红细胞2相关因子2(Nrf2)及血红素加氧酶1(HO-1)的表达水平。结果与正常对照组比较,缺氧模型组血清CK和LDH活性升高,心肌组织H2O2和MDA含量升高,心肌组织SOD、CAT和GSH-Px活性降低,心肌组织Nrf2和HO-1表达升高(P<0.01)。与缺氧模型组比较,芦丁组和黄芩素-7-甲醚组血清CK和LDH活性降低,心肌组织H2O2和MDA含量降低,心肌组织SOD、CAT和GSH-Px活性升高,心肌组织Nrf2和HO-1蛋白表达进一步升高(P<0.01)。结论黄芩素-7-甲醚对模拟高原缺氧导致的心肌组织损伤具有一定的保护作用,机制可能与清除自由基、激活Nrf2/HO-1信号途径、提高抗氧化酶活性、降低机体氧化应激水平有关.Objective To study protective effect of Negletein on hypobaric hypoxia-induced myocardial tissue damage in mice. Methods A total of 40 male BALB/C mice were randomly divided into control group (lavaged with water for injection, n =10), hypoxia model group (lavaged with water for injection, n =10), Rutin group (lavaged with 500 mg/kg Rutin, n =10) and Negletein group (lavaged with 500 mg/kg Negletein, n =10). Except for control group, the other three groups were exposed to simulated altitude environment of 8000 m for 12 h, and then all the mice were taken blood from the orbit to detect activities of serum lactate dehydrogenase (LDH) and creatine kinase (CK). Finally, the myocardial tissues were taken after mice had been sacrificed to detect contents of hydrogen peroxide (H 2O 2) and malondialdehyde (MDA), activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px), and expressions of nuclear factor red blood cell-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). Results Compared with those in control group, serum CK and LDH activities were increased, and H 2O 2 and MDA contents in myocardial tissues were increased, and SOD, CAT and GSH-Px activities in myocardial tissues were decreased, and Nrf2 and HO-1 expression in myocardial tissues were increased in hypoxic model group ( P <0.01). Compared with those in hypoxia model group, serum CK and LDH activities were decreased, and contents of H 2O 2 and MDA in myocardial tissues were decreased, while activities of SOD, CAT and GSH-Px in myocardial tissues were increased, and expressions of Nrf2 and HO-1 proteins in myocardial tissues were further increased in Rutin and Negletein groups ( P <0.01). Conclusion Negletein has a certain protective effect on hypobaric hypoxia-induced myocardial tissue damage, and its mechanism may be related to scavenging free radicals, activating Nrf2/HO-1 signaling pathway, increasing antioxidant enzyme activity and reducing oxidative stress level.

关 键 词：黄芩素-7-甲醚 缺氧 心脏损伤 氧化性应激 小鼠 近交BALB C 

分 类 号：R594.3[医药卫生—内科学] R-332[医药卫生—临床医学]