甜菜碱调控丝裂原活化蛋白激酶通路抑制大鼠急性心肌缺血的作用  

Inhibitory effects of betaine on acute myocardial ischemic rats via regulation of MAPK pathway

作　　者：郑萍[1,2] 买淑霞 刘俊梅[1,2] 李娟[1,2] 王洋[1,2] 袁娅妮 戴贵东[3] 

机构地区：[1]宁夏医科大学药学院,宁夏银川750004 [2]宁夏用药现代化工程技术研究中心,宁夏银川750004 [3]凯里学院化学与材料工程学院,贵州凯里556011

出　　处：《中国医院药学杂志》2014年第21期1800-1805,共6页Chinese Journal of Hospital Pharmacy

基　　金：国家自然科学基金资助项目(编号:81160403)

摘　　要：目的:探讨甜菜碱对异丙肾上腺素(ISO)诱导的大鼠急性缺血性心肌损伤的保护作用及其对MAPK通路的影响。方法:SD雄性大鼠皮下注射ISO(85 mg·kg-1·d-1,qd,连续2 d)建立急性心肌缺血模型,研究甜菜碱(100,200,400 mg·kg-1·d-1)灌胃给药40 d对缺血性心肌病理结构、抗氧化酶活力、脂质过氧化物含量及MAPK通路相关蛋白表达的影响。结果:甜菜碱(100,200,400 mg·kg-1·d-1)对急性心肌缺血心肌病理结构的损伤具有保护作用,可升高ISO致急性心肌缺血大鼠心肌组织中T-AOC、SOD、GSH-PX的活力,并相应降低脂质过氧化物MDA的含量。甜菜碱(400 mg·kg-1·d-1)显著降低pERK1/2蛋白的表达,并增加p-JNK和p-p38 MAPK蛋白的表达(P<0.01)。单用甜菜碱(400 mg·kg-1·d-1)除可降低ERK1/2的表达外,对心肌组织结构、抗氧化物酶活性及脂质过氧化物含量及其他MAPK通路蛋白表达均无影响。结论:大剂量甜菜碱对异丙肾上腺素致大鼠急性心肌缺血性损伤的保护作用可能与MAPK通路有关。OBJECTIVE To investigate the cardio-protective effect of betaine against isoproterenol （ISO）-induced acute myo- cardial ischemic injury, and its action on MAPK pathway. METHODS Male Sprague-Dawley rats were pretreated with betaine （100, 200,400 mg·kg^-1·d^-1） daily for a period of 40 days. ISO （85 mg·kg^-1·d^-1） was injected subcutaneously into rats twice at an interval of 24 h to induce acute myocardial ischemia. Cardiac histo- pathological parameters, oxidant- antioxidant status, and protein expression relevant to MAPK pathway were measured. RESULTS Betaine （100, 200, 400 mg·kg^-1·d^-1 ） treatment significantly attenuated isoproterenol-induced myocardial ischemia as evident by cardiac histo-pathological alterations, increased in myocardial T-AOC, SOD and GSH-PX activites along with a decreased in MDA level. Betaine （400 mg·kg^-1·d^-1 ） significantly decreased the expression of p-ERK1/2 protein, and increased expression of p-JNK and p-p38 MAPK protein （P〈0. 01）. Compared with control group, betaine （400 mg·kg^-1·d^-1） alone reduced the expression of ERK1/2, but had no effect on any other indexes in sham rats. CONCLUSION The results suggested that high doses of betaine protected rats against iso- proterenol-induced acute myocardial ischemia maybe related to the regulation of MAPK pathways.

关 键 词：甜菜碱 心肌缺血 丝裂原活化蛋白激酶(MAPK) 异丙肾上腺素 抗氧化 

分 类 号：R966[医药卫生—药理学]