线粒体分裂通过促进脂肪酸氧化改善糖尿病小鼠心脏功能的机制研究  

Mechanism of mitochondrial division improving cardiac function in diabetic mice by promoting fatty acid oxidation

作　　者：丁小艳 陈永清 宋小刚 吕丽丽 翟满满 吴冰 Ding Xiaoyan;Chen Yongqing;Song Xiaogang;LüLili;Zhai Manman;Wu Bing(Department of Geriatrics,No.940 Hospital of Joint Logistics Support force of Chinese PLA,Lanzhou 730000,Gansu Province,China)

机构地区：[1]解放军联勤保障部队第九四〇医院老年科,兰州730000 [2]甘肃省中心医院心内科 [3]西安市中心医院心内科

出　　处：《中华老年心脑血管病杂志》2024年第12期1477-1482,共6页Chinese Journal of Geriatric Heart,Brain and Vessel Diseases

基　　金：甘肃自然科学基金(23JRRA1377);兰州市科技计划项目(2022-5-84);解放军联勤保障部队第九四〇医院院内项目(2021yxky038);甘肃省卫生健康行业科研计划项目(GSWSKY2020-13)。

摘　　要：目的探讨线粒体分裂调控糖尿病小鼠心肌脂肪酸氧化的机制。方法选择7周龄雄性SPF级C57BLKS/J糖尿病小鼠16只,随机分为模型组和mdivi-1(线粒体分裂抑制剂1)干预组(干预组),每组8只,以同龄雄性SPF级C57BLKS/J小鼠8只为对照组,适应性喂养1周。监测小鼠血糖及体质量变化,超声心动图测定各组小鼠左心室射血分数(Left ventricular ejection fraction,LVEF)、左心室短轴缩短率(Left ventricular fractional shortening,LVFS)及心室舒张早期与心室舒张末期的血流流速比值(E/A)水平。苏木精-伊红染色观察心肌组织病理结构变化;透射电镜观察线粒体大小、形态和数量;Western blotting检测线粒体动力相关蛋白1(dynamin-related protein 1,Drp1)、脂肪酸氧化调控蛋白过氧化物酶体增殖物激活受体α(peroxisome proliferator activated receptorα,PPARα)、长链酰基辅酶A合成酶4(long-chain acyl-CoA synthetase 4,ACSL4)、肉碱棕榈酰转移酶1B(carnitine palmitoyl transferase 1B,CPT1B)表达水平,脂肪酸氧化检测试剂盒测定脂肪酸氧化活性。结果与对照组比较,模型组小鼠可见心肌细胞肥大,心肌细胞横截面直径明显高于对照组,差异有统计学意义[(22.36±2.80)μm vs(12.71±1.78)μm,P<0.01];与模型组比较,干预组小鼠心肌肥大程度明显改善,心肌细胞横截面直径明显低于模型组,差异有统计学意义[(13.79±1.39)μm vs(22.36±2.8)μm,P<0.01]。模型组小鼠心肌线粒体Drp1表达水平,心肌组织单位面积内线粒体个数,心肌细胞质中PPARα、ACSL4、CPT1B蛋白表达明显高于对照组,心肌组织单个线粒体平均面积和心肌线粒体中PPARα、ACSL4、CPT1B及心肌组织脂肪酸氧化活性明显低于对照组,差异有统计学意义(P<0.01)。Mdivi-1干预后,干预组小鼠心肌线粒体Drp1表达水平,心肌组织单位面积内线粒体个数,心肌细胞质中PPARα、ACSL4、CPT1B蛋白表达明显低于模型组,心肌组织单个线粒体平均面积�Objective To investigate the mechanism of mitochondrial division regulating myocardial fatty acid oxidation in diabetic mice.Methods A total of 167-week-old male SPF C57BLKS/J diabetic mice were randomly divided into model group and mitochondrial division inhibitor 1(mdivi-1)intervention group(intervention group),with 8 mice in each group.Another 8 male SPF C57BLKS/J mice of the same age were fed adaptively for 1 week and served as control group.The changes in blood glucose and body mass were monitored in above groups.Echocardiography was conducted to detect LVEF and LVFSl rate and E/A between early and late ventricular diastole.The pathological changes of myocardial tissue were observed by HE staining.The size,morphology and quantity of mitochondria were observed by TEM.Western blotting was used to detect the expression of mitochondrial dynamin-related protein 1(Drp1),peroxisome proliferator activated receptorα(PPARα),long chain acyl-CoA synthetase 4(ACSL4),carnitine palmitoyl transferase 1B(CPT1B),and fatty acid oxidation detection kit was conducted to determine the activity of fatty acid oxidation.Results Compared with the control group,the model group presented hypertrophic cardiomyocytes and significantly larger cross-sectional diameter of cardiomyocytes(22.36±2.80μm vs 12.71±1.78μm,P<0.01)than the control group.Mdivi-1 intervention resulted in greatly improved myocardial hypertrophy and obviously smaller cross-sectional diameter of cardiomyocytes(13.79±1.39μm vs 22.36±2.8μm,P<0.01)when compared with the model group.The expression level of myocardial mitochondrial Drp1,number of mitochondria per unit area of myocardial tissue and the protein levels of PPARα,ACSL4 and CPT1B in myocardial cytoplasm were significantly higher,and the average mitochondrial area of myocardial tissue,the expression of PPARα,ACSL4 and CPT1B in myocardial mitochondria,and fatty acid oxidation activity were significantly lower in the model group than the control group(P<0.01).After mdivi-1 intervention,the expression level

关 键 词：糖尿病 模型 动物 线粒体动力学 过氧化脂质类 心肌 

分 类 号：R587.1[医药卫生—内分泌] R-332[医药卫生—内科学]