| 心脏Nmnat过表达联合耐力运动对果蝇高脂膳食诱发脂毒性心肌症的影响 |
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| 引用本文： | 文登台,郑澜,陆凯,刘宪楚,后文其.心脏Nmnat过表达联合耐力运动对果蝇高脂膳食诱发脂毒性心肌症的影响[J].首都体育学院学报,2020(1):87-96. |
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| 作者姓名： | 文登台 郑澜 陆凯 刘宪楚 后文其 |
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| 作者单位： | 湖南师范大学体适能与运动康复湖南省重点实验室;鲁东大学 |
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| 基金项目： | 国家自然科学基金资助项目（31671243）;国家青年基金资助项目（81600320） |
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| 摘 要： | 利用UAS/hand-gal4系统构建果蝇心脏Nmnat基因特异性过表达,研究心脏Nmnat基因过表达联合耐力运动对高脂膳食诱发脂毒性心肌症的影响,并分析其分子机制。方法:雄性w^1118和NmnatUAS系果蝇分别与雌性hand-Gal4杂交,收集F1代心脏Nmnat正常表达(hand>w^1118)和过表达(hand>Nmnat)处女蝇,饲养至15 d后开始进行耐力运动(E)和高脂膳食(HFD),并分为hand>w^1118、hand>w^1118+E、hand>w^1118+HFD、hand>w^1118+HFD+E、hand>Nmnat、hand>Nmnat+E、hand>Nmnat+HFD、hand>Nmnat+HFD+E共8组,每组410只。ELISA检测心脏TAG、NAD+、SIR2蛋白去乙酰化、SOD活力和MDA水平,qRT-PCR检测心脏相关基因mRNA表达,M-mode检测心脏功能情况。结果:hand>w^1118+HFD+E果蝇心脏的Nmnat、dFoxo、bmm表达、NAD+水平、SIR2去乙酰化、SOD活力、缩短分数高于hand>w^1118+HFD(P<0.05或P<0.01),且d FAS和Col4al表达、TAG和MDA水平、心率和纤维性振颤低于hand>w^1118+HFD(P<0.05或P<0.01);hand>Nmnat果蝇心脏各指标与hand>Nmnat+HFD相比较未见显著差异(P>0.05);hand>Nmnat+HFD+E果蝇心脏的Nmnat、dFoxo、bmm表达、心脏NAD+水平、SIR2去乙酰化、SOD活力、心脏缩短分数高于hand>Nmnat+HFD(P<0.05或P<0.01),且dFAS和Col4al表达\TAG和MDA水平、心率和纤维性振颤低于hand>Nmnat+HFD(P<0.05或P<0.01)。结论:心脏Nmnat过表达和耐力运动均能抵抗果蝇高脂膳食诱发的心脏脂质过度堆积、氧化损伤、减弱心脏收缩能力和增加纤维性振颤,其分子机制与心脏Nmnat/NAD+/SIR2/dFoxo通路活性增强有关。心脏Nmnat基因过表达联合耐力运动能更好地降低脂毒性心肌症的发生概率,其机制与二者联合对心脏Nmnat/NAD+/SIR2/dFoxo通路活性上调的叠加作用有关。
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| 关 键 词： | 耐力运动 高脂膳食 脂毒性心肌症 Nmnat |
Effects of Cardiac Nmnat Overexpression Combined with Endurance Exercise on High-fat Diet Induced Lipotoxic Cardiomyopathy in Drosophila |
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| WEN Dengtai,ZHENG Lan,LU Kai,LIU Xianchu,HOU Wenqi.Effects of Cardiac Nmnat Overexpression Combined with Endurance Exercise on High-fat Diet Induced Lipotoxic Cardiomyopathy in Drosophila[J].Journal of Capital College of Physical Education,2020(1):87-96. |
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| Authors: | WEN Dengtai ZHENG Lan LU Kai LIU Xianchu HOU Wenqi |
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| Institution: | (Key Laboratory of Physical Fitness and Exercise Rehabilitation,Hunan Normal University Changsha,Hunan 410012,China;Department of Physical Education,Ludong University,Yantai,Shandong 264025,China) |
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| Abstract: | Objective:Constructing the specific overexpression of Nmnat gene in the heart of fruit flies using UAS/hand-gal4 system to study the effect of the overexpression of Nmnat gene in the heart combined with endurance exercise on lipid toxicity induced by high-fat diet,and to analyze the molecular mechanism.Methods:Male w^1118 and Nmnat-UAS fruit flies were respectively hybridized with female hand-gal4.Collecting the normal expression of heart Nmnat(hand>w^1118)and the overexpression(hand>Nmnat)of F1 generation female flies.After feeding for 15 days,they began to perform endurance exercise(E)and high-fat diet(HFD).They were divided into hand>w^1118,hand>w^1118+E,hand>w^1118+HFD,hand>w^1118+HFD+E,hand>Nmnat,hand>Nmnat+E,hand>Nmnat+HFD,hand>Nmnat+HFD+E,410 flies in each group.The levels of cardiac TAG,NAD+,SIR2 protein deacetylation,SOD activity and MDA were detected by ELISA.The expression of cardiac related genes by RT-PCR;M-mode detects cardiac function.Results:the expression of Nmnat,d Foxo,bmm,NAD+level,SIR2 deacetylation,SOD activity and shortened fraction of hand>w^1118+HFD+E group were significantly higher than that of hand>w^1118+HFD group(P<0.05 or P<0.01),but the expression of d FAS,Col4 al,TAG and MDA level,heart rate and fibrillation were significantly lower than that of hand>w^1118+HFD group(P<0.05 or P<0.01).There was no significant difference between the heart hand>Nmnat group and hand>Nmnat+HFD group(P>0.05).The expression of Nmnat,d Foxo,bmm,NAD+,SIR2 deacetylation,SOD activity and shortened heart fraction in the hand>Nmnat+HFD+E group were significantly higher than those in the hand>Nmnat+HFD group(P<0.05 or P<0.01),but the expression of d FAS,Col4 al,TAG and MDA levels,heart rate and fibrillation were significantly lower than those in the hand>Nmnat+HFD group(P<0.05 or P<0.01).Conclusion:both overexpression of cardiac Nmnat and endurance exercise can prevent excessive accumulation of cardiac lipids,oxidative damage,decreased cardiac contractility and increased fibrillation induced by high-fat diet.The molecular mechanism is related to the fact that both of them can up-regulate the activity of cardiac Nmnat/NAD+/SIR2/d Foxo pathway.The overexpression of cardiac Nmnat gene combined with endurance exercise can better reduce the occurrence of lipid toxic cardiomyopathy,which is related to the superposition effect of the combination on the up-regulation of cardiac Nmnat/NAD+/SIR2/d Foxo pathway activity. |
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| Keywords: | endurance exercise high-fat-diet lipotoxic cardiomyopathy Nmnat |
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