高锌饮食通过调控AMPK-Drp1通路对链脲霉素诱导的1型糖尿病小鼠心肌损伤的保护作用  

Protective effect of high zinc diet on streptozotocin-induced myocardial injury in type 1 diabetic mice through adenine monophosphate activated protein kinase/dynamin related protein 1 pathway

作　　者：纪磊[1] 刘盈盈[2] 张欢[2] 吴倩 刘波[3] Ji Lei;Liu Yingying;Zhang Huan;Wu Qian;Liu Bo(Department of Cardiology,China-Japan Union Hospital of Jilin University,Changchun 130051,China;Department of Nephrology,China-Japan Union Hospital of Jilin University,Changchun 130051,China;Emergency Department,Beijing Chaoyang Hospital,Capital Medical University,Beijing 100043,China)

机构地区：[1]吉林大学中日联谊医院心内科,长春130051 [2]吉林大学中日联谊医院肾病内科,长春130051 [3]首都医科大学附属北京朝阳医院急诊科,100043

出　　处：《中华糖尿病杂志》2021年第7期713-719,共7页CHINESE JOURNAL OF DIABETES MELLITUS

摘　　要：目的观察补锌治疗对1型糖尿病(T1DM)心肌病小鼠心肌腺苷酸活化蛋白激酶(AMPK)、线粒体动力相关蛋白1(Drp1)及氧化应激水平的变化,初步探讨锌对糖尿病心肌病保护作用的分子机制。方法取8周龄雄性FVB小鼠60只,通过小剂量(50 mg/kg)链脲霉素连续腹腔注射5 d的方法构建T1DM心肌损伤小鼠模型。造模成功后将小鼠通过整群随机抽样方法分为3组,分别为对照组(A组,20只)、糖尿病心肌损伤模型组(B组,18只)和模型+高锌饮食组(C组,18只)。A组和B组给予正常锌饮食(锌含量为30 mg/kg),C组给予高锌饮食(锌含量150 mg/kg),饲养时间均为3个月。测量小鼠体重;检测血清葡萄糖、丙二醛、超氧化物歧化酶水平;心脏彩色超声多普勒测量小鼠心脏功能,测量左室射血分数(EF)、收缩期和舒张期心室充盈早期峰值速度、晚期充盈速度的比值(E/A比值)和左室舒张末期内径(LVDD);观察心肌组织病理学改变,并检测AMPK、磷酸化腺苷酸活化蛋白激酶(pAMPK^(Thr172))、Drp1和磷酸化动力相关蛋白1(pDrp1^(Ser616))的蛋白表达水平,计算pAMPK^(Thr172)/AMPK和pDrp1^(Ser616)/Drp1比值。多组间比较采用单因素方差分析方法。结果A、B、C三组间,体重、血糖、丙二醛和超氧化物歧化酶水平、E/A比值、EF值和LVDD的差异均有统计学意义(P<0.05),其中B组血浆丙二醛水平较A组升高,超氧化物歧化酶水平较A组降低,而C组较B组丙二醛水平降低,超氧化物歧化酶水平较B组升高,差异有统计学意义(P<0.05)。与A组相比,B组小鼠E/A比值和EF值降低,而C组较B组增加,差异有统计学意义(P<0.05)。与A组相比,B组的pAMPK^(Thr172)/AMPK值降低,而C组较B组升高,差异有统计学意义(P<0.05);与A组相比,B组的pDrp1^(Ser616)/Drp1值增加,C组较B组降低,差异有统计学意义(P<0.05)。补锌治疗增加了心肌AMPK蛋白Thr172位点磷酸化水平,减少了Drp1蛋白Ser616位点磷酸化水平(P<0.05)。结论补�Objective To observe the effect of zinc supplementation on the changes of myocardial adenine monophosphate activated protein kinase(AMPK),dynamin related protein 1(Drp1)and oxidative stress in type 1 diabetic mice(T1DM),and to preliminarily explore the mechanism of the protective effect of zinc treatment on diabetic cardiomyopathy.Methods Sixty eight-week-old male FVB mice were selected,and a small dose(50 mg/kg)of streptozocin(STZ)was continuously injected intraperitoneally for five days to construct a T1DM myocardial injury mouse model.After successful modeling,the mice were divided into three groups by block randomization:control group(group A,n=20),diabetic myocardial injury group(group B,n=18)and diabetic myocardial injury model+high zinc diet group(group C,n=18).Groups A and B were given normal zinc diet(the content of zinc is 30 mg/kg)and group C was given a high-zinc diet(the content of zinc was 150 mg/kg)for 3 months.The body weight,serum glucose,malondialdehyde and superoxide dismutase levels were measured;the cardiac function,left ventricular ejection fraction(EF value),the ratio of the early peak and late filling rates of systolic and diastolic ventricles(E/A ratio)and left ventricular end diastolic diameter(LVDD)were also detected;the pathological changes of myocardial tissue were observed.Furthermore,the protein expressions of AMPK,phospho adenine monophosphate activated protein kinase(pAMPK^(Thr172)),Drp1 and phospho dynamin related protein1(pDrp1ser616)were measured by Western blotting,and the ratios of pAMPK^(Thr172)/AMPK and pDrp1^(Ser616)/Drp1 were calculated.One-way analysis of variance(ANOVA)was used for comparison among multiple groups.Results The differences in weight,blood glucose,malondialdehyde and superoxide dismutase levels,E/A ratio,EF value and LVDD among the three groups A,B,and C were statistically significant(P<0.05).The levels of plasma malondialdehyde were higher and superoxide dismutase were lower in group B compared with those of group A,while the levels of malondialdehyde wer

关 键 词：糖尿病 心肌损伤 锌 氧化应激 

分 类 号：R587.2[医药卫生—内分泌] R542.2[医药卫生—内科学]