左卡尼汀对自然衰老模型大鼠的心脏保护作用及其分子机制研究  

Protective Effect of Levocarnitine on the Heart of Natural Aging Rats and Its Molecular Mechanism

作　　者：张珍[1] 张霞 刘春 蔡文升 李雪辉 邢艳秋[1] ZHANG Zhen;ZHANG Xia;LIU Chun;CAI Wensheng;LI Xuehui;XING Yanqiu(Department of Geriatric Medicine,Qilu Hospital of Shandong University/Key Laboratory of Cardiovascular Disease Proteomics of Shandong Province,Jinan 250012,China;Department of Cardiology,Rizhao Central Hospital,Rizhao 276800,China;Department of Internal Medicine-Cardiovascular,the Fourth People's Hospital of Jinan,Jinan 250031,China;Department of Vascular Surgery,Rizhao Central Hospital,Rizhao 276800,China)

机构地区：[1]山东大学齐鲁医院老年医学科,山东省心血管疾病蛋白质组学重点实验室,山东省济南市250012 [2]山东省日照市中心医院心内科,276800 [3]山东省济南市第四人民医院心内科,250031 [4]山东省日照市中心医院血管外科,276800

出　　处：《实用心脑肺血管病杂志》2020年第11期66-70,共5页Practical Journal of Cardiac Cerebral Pneumal and Vascular Disease

基　　金：国家自然科学基金资助项目(81570356,81700725);山东省重点研发计划项目(2017GSF218014,2017GSF218101)。

摘　　要：背景左卡尼汀是重要的线粒体能量代谢调节物,其对衰老心脏是否具有保护作用尚不明确。目的以自然饲养的24月龄大鼠来构建自然衰老动物模型,研究左卡尼汀对自然衰老模型大鼠的心脏保护作用,并深入分析其分子机制。方法2017年1月—2019年6月,选取3月龄SPF级雄性大鼠30只。将在标准饲养环境下自然饲养至4月龄的大鼠作为青年对照组(n=10)。将在标准饲养环境下自然饲养至24月龄的大鼠随机分为左卡尼汀组(n=10)和老年对照组(n=10)。左卡尼汀组大鼠给予左卡尼汀300 mg·kg^-1·d^-1,老年对照组大鼠给予等量0.9%氯化钠溶液,均连续灌胃4周。记录并比较各组大鼠心脏收缩、舒张功能指标〔包括左心室舒张末期内径(LVEDD)、左心室收缩末期内径(LVESD)、左心室舒张末期容积(LVEDV)、左心室收缩末期容积(LVESV)、左心室射血分数(LVEF)、左心室短轴缩短率(LVFS)〕,血清丙二醛(MDA)水平、超氧化物歧化酶(SOD)活性,线粒体超微结构,心肌组织三磷酸腺苷(ATP)、磷酸化-AMP依赖的蛋白激酶(p-AMPK)、肉毒碱脂酰转移酶1(CPT-1)水平。结果老年对照组LVEDD、LVESD、LVEDV、LVESV大于青年对照组(P<0.05);左卡尼汀组LVESD、LVESV小于青年对照组,LVEF、LVFS高于青年对照组(P<0.05);左卡尼汀组LVEDD、LVESD、LVEDV、LVESV小于老年对照组,LVFS高于老年对照组(P<0.05)。老年对照组血清MDA水平高于青年对照组,SOD活性小于青年对照组(P<0.05);左卡尼汀组血清MDA水平高于青年对照组(P<0.05);左卡尼汀组血清MDA水平低于老年对照组,SOD活性大于老年对照组(P<0.05)。与青年对照组大鼠相比,老年对照组大鼠线粒体形态各异,部分线粒体肿胀明显,基质出现多个局灶性空泡;与老年对照组相比,左卡尼汀组大鼠心肌细胞线粒体体积明显缩小,偶见空泡变性,线粒体嵴排列整齐致密。老年对照组心肌组织ATP水平低于青年对照组(P<0.05);左Background Levocarnitine palys an important role in mitochondrial energy metabolism,but whether it possesses protective effects on aging heart is unclear.Objective A natural aging animal model was constructed with 24 month-old rats fed naturally to study the protective effect of levocarnitine on the natural aging model rats,and its molecular mechanism was further analyzed.Methods A total of 30 three-month-old male SPF rats were selected from January 2017 to June 2019.Rats naturally raised to 4 months old in standard feeding environment were used as young control group(n=10).Rats naturally raised to 24 months old in standard feeding environment were randomly divided into the levocarnitine group(n=10)and the elderly control group(n=10).Rats in the levocarnitine group were given levocarnitine 300 mg·kg^-1·d^-1,and the rats in the elderly control group were given the same volume of 0.9%sodium chloride solution,and they were all fed for 4 weeks.The indexes of cardiac systolic and diastolic function(including LVEDD,LVESD,LVEDV,LVESV,LVEF,LVFS),serum MDA level,SOD activity,mitochondrial ultrastructure,levels of myocardial tissue ATP,p-AMPK,CPT-1 of rats were recorded and compared in each group.Results LVEDD,LVESD,LVEDV and LVESV in the elderly control group were larger than those in the young control group(P<0.05);LVESD and LVESV in the levocarnitine group were smaller than those in the young control group,and LVEF and LVFS were higher than those in the young control group(P<0.05);LVEDD,LVESD,LVEDV and LVESV in the levocarnitine group were smaller than those in the elderly control group,and LVFS was higher than that in the elderly control group(P<0.05).The serum MDA level of the elderly control group was higher than that of the young control group,and the SOD activity was lower than that of the young control group(P<0.05);the serum MDA level in the levocarnitine group was higher than that of the young control group(P<0.05);the serum MDA level in the levocarnitine group was lower than that in the elderly control group,

关 键 词：衰老 左卡尼汀 大鼠 心脏 AMP依赖的蛋白激酶 肉毒碱脂酰转移酶1 

分 类 号：R33[医药卫生—人体生理学]