钠钾泵抑制剂pNaKtide对糖尿病心肌病小鼠心脏损伤的作用  

Effects of sodium potassium pump inhibitor pNaKtide on diabetic cardiomyopathy mice

作　　者：张晓天 亢梦婕 董嘉薇 卓坤萍 甄艳茹 周明生 徐茜 ZHANG Xiaotian;KANG Mengjie;DONG Jiawei;ZHUO Kunping;ZHEN Yanru;ZHOU Mingsheng;XU Qian(Department of Pathology and Pathophysiology,Basic Medical College,Shenyang Medical College,Shenyang 110034;Department of Clinical Medicine,Shenyang Medical College,Shenyang 110034;Scientific Experiment Center,Shenyang Medical College,Shenyang 110034)

机构地区：[1]沈阳医学院基础医学院病理学与病理生理学系,沈阳110034 [2]沈阳医学院临床医学系,沈阳110034 [3]沈阳医学院科学实验中心,沈阳110034

出　　处：《郑州大学学报（医学版）》2023年第2期153-157,共5页Journal of Zhengzhou University(Medical Sciences)

基　　金：国家自然科学基金项目(82270434);沈阳医学院大学生创新创业训练计划项目(20219027)。

摘　　要：目的:探讨钠钾泵抑制剂pNaKtide对糖尿病心肌病小鼠心脏损伤的作用及机制。方法:自发性2型糖尿病心肌病(leptin基因敲除)db/db小鼠和野生wt小鼠各8只,分为4组:db/db组、db/db+pNaKtide组、wt组和wt+pNaKtide组,每组各4只。db/db+pNaKtide组和wt+pNaKtide组小鼠按10 mg/kg每周腹腔注射pNaKtide 1次,wt组和db/db组注射生理盐水,共8周。每周测量体重及小鼠尾动脉收缩压(SBP)。干预8周后检测小鼠血清甘油三酯及总胆固醇水平;HE和Masson染色评价心脏损伤和心肌纤维化程度,DHE染色观察活性氧(ROS)生成情况。结果:干预8周后db/db小鼠体重增加,pNaKtide干预后小鼠体重增加减少;db/db小鼠SBP升高,pNaKtide干预后降低(P<0.05)。db/db小鼠心肌细胞横截面积和纤维化面积百分比增大,pNaKtide干预后减小(P<0.05)。db/db小鼠血清甘油三酯及总胆固醇水平升高,pNaKtide干预后降低(P<0.05)。db/db小鼠产生大量ROS,pNaKtide干预后降低(P<0.05)。结论:抑制钠钾泵激活能有效改善糖尿病心肌病小鼠的心脏损伤,其机制可能与下调ROS生成,降低氧化应激水平有关。Aim:To investigate the effects and mechanism of sodium potassium pump inhibitor pNaKtide on cardiac injury in diabetic cardiomyopathy mice.Methods:Eight spontaneous type 2 diabetic cardiomyopathy(leptin gene knockout)db/db mice and eight wild type(wt)mice were allocated into 4 groups,db/db group,db/db+pNaKtide group,wt group and wt+pNaKtide group with 4 mice in each group.Mice in db/db+pNaKtide group and wt+pNaKtide group were intraperitoneally injected with pNaKtide at a dose of 10 mg/kg once a week,while mice in wt group and db/db group were injected with normal saline for 8 weeks.Body weight and caudal systolic pressure(SBP)of mice were measured every week.After 8 weeks of intervention,serum triglyceride and total cholesterol levels of mice were determined.HE and Masson staining were used to evaluate the degree of heart injury and myocardial fibrosis,and DHE staining was used to observe the production of reactive oxygen species(ROS).Results:After 8 weeks,the weight of db/db mice increased,but the weight increased slowly after pNaKtide intervention(P<0.05).SBP increased in db/db mice,and pNaKtide intervention attenuated the increased SBP in db/db mice(P<0.05).Myocardial cell cross sectional area and percentage of fibrotic area of db/db mice were increased,which were decreased after pNaKtide intervention(P<0.05).The levels of serum triglyceride and total cholesterol increased in db/db mice,which decreased after pNaKtide intervention(P<0.05).A lot of ROS was produced in db/db mice,which decreased after pNaKtide intervention(P<0.05).Conclusion:Inhibiting the activation of sodium potassium pump can effectively improve the heart injury in diabetic cardiomyopathy mice,and its mechanism may be related to down-regulating ROS production and reduce the level of oxidative stress.

关 键 词：钠钾泵 pNaKtide 糖尿病心肌病 心肌肥大 心肌纤维化 氧化应激 小鼠 

分 类 号：R587.1[医药卫生—内分泌]