荠苧黄酮对低压低氧小鼠心肌组织损伤的改善作用与机制研究  

Ameliorative effect and mechanism of mosloflavone on hypobaric hypoxia-induced heart damage in mice

作　　者：刘睿 邵瑾 赵彤 马慧萍 何蕾 景临林 LIU Rui;SHAO Jin;ZHAO Tong;MA Hui-ping;HE Lei;JING Lin-lin(Cadre Ward,The 940th Hospital of Joint Logistics Support Force of PLA,Lanzhou 730050,China;Department of Pharmacy,the 940th Hospital of Joint Logistics Support Force of PLA,the Lab of PLA for High Altitude Medicine,Lanzhou 730050,China)

机构地区：[1]联勤保障部队第九四〇医院干部病房,兰州730050 [2]联勤保障部队第九四〇医院全军高原医学重点实验室药剂科,兰州730050

出　　处：《中国新药杂志》2021年第1期55-61,共7页Chinese Journal of New Drugs

基　　金：国家自然科学基金项目(81872796,81202458,81571847);军队后勤科研计划(CWH17J010);甘肃省自然科学基金(18JR3RA408,1308RJYA061,145RJZA089);中国博士后科学基金(2012M521926)。

摘　　要：目的:研究荠苧黄酮对低压低氧小鼠心肌组织损伤的改善作用与机制。方法:将60只小鼠随机分为正常对照组、缺氧模型组、芦丁组和荠苧黄酮组,连续灌胃(ig)给药5 d,最后1次给药后,在模拟海拔8000 m环境停留12 h,测定血清中肌酸激酶(creatine kinase,CK)、乳酸脱氢酶(lactic dehydrogenase,LDH)、谷草转氨酶(aspartate transaminase,AST)、心肌肌钙蛋白Ⅰ(cardiac troponinⅠ,cTnⅠ)活性,测定心肌组织中活性氧(reactive oxygen species,ROS)、丙二醛(malondialdehyde,MDA)、谷胱甘肽(glutathione,GSH)、超氧化物歧化酶(superoxide dismutase,SOD)、过氧化物酶(catalase,CAT)、谷胱甘肽过氧化物酶(glutathione peroxidase,GSH-Px)和ATPase的含量和活性。蛋白印迹法检测Bcl-2和Bax蛋白的表达水平。结果:与正常对照组相比,缺氧模型组小鼠血清中CK,LDH,AST和cTnⅠ的水平显著增加,心肌组织中ROS和MDA含量显著升高,抗氧化酶、GSH和ATPase水平显著下降,Bax蛋白表达增强,Bcl-2蛋白的表达和Bc1-2/Bax比值降低。经荠苧黄酮预处理能够显著降低缺氧小鼠血清中损伤因子的水平,显著降低小鼠心肌组织中ROS和MDA的含量,提高GSH的水平,维持抗氧化酶和ATPase的活力,降低Bax蛋白表达,提高Bc1-2/Bax比值。结论:荠苧黄酮通过降低心肌氧化应激、改善能量代谢、调节凋亡相关蛋白,对低压低氧诱导的心肌组织损伤具有明显保护作用。Objective:To assess the protective effect and mechanism of mosloflavone against heart damage induced by hypobaric hypoxia(HH)in mice.Methods:60 male BALB/c mice were randomly divided into four groups:control group,hypoxia group,rutin group and mosloflavone group.The mice were orally treated for 5 days with drugs or water and then exposed to HH equivalent to 8000 m for 12 h.Serum concentrations of lactic dehydrogenase(LDH),creatine kinase(CK),aspartate transaminase(AST)and cardiac troponinⅠ(cTnⅠ)were assessed.The levels of reactive oxygen species(ROS),malondialdehyde(MDA)and glutathione(GSH),as well as the activities of superoxide dismutase(SOD),catalase(CAT),glutathione peroxidase(GSH-Px)and ATPase,in heart were estimated.The expression of Bax and Bcl-2 were evaluated by Western blot analysis.Results:Compared with control group,the levels of LDH,CK,AST and cTnⅠin serum in hypoxia model group significantly increased.In addition,HH markedly increased the contents of ROS and MDA and decreased the GSH contents and the activities of SOD,CAT,GSH-Px and ATPase in heart.Furthermore,HH significantly unregulated the expression of Bax and downregulated the expression of Bc1-2.In contrast,mosloflavone alleviated heart damage induced by HH as evidence of reduced LDH,CK,AST and cTnⅠlevels in serum.Prior administration of mosloflavone also decreased the ROS and MDA contents,increased GSH level,SOD,CAT,GSH-Px,Na+-K+-ATPase and Ca2+-Mg2+-ATPase activities,downregulated the expression of Bax,as well as increased the expression ratio of Bax/Bc1-2 in heart tissue of mice.Conclusion:Mosloflavone exhibited protective effect against HH induced heart injury in mice via alleviating of oxidative stress,ameliorating of energy metabolism,as well as regulating of apoptosis related proteins.

关 键 词：荠苧黄酮 低压低氧 心肌损伤 氧化应激 凋亡 

分 类 号：R965.1[医药卫生—药理学]