自噬相关通路在糖尿病心肌病中的研究进展
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摘要
糖尿病心肌病定义为无冠状动脉疾病和高血压的糖尿病患者发生的心肌功能障碍。据报道,糖尿病心肌病的发病机制与炎症、心肌纤维化、线粒体损伤、心肌细胞凋亡、自噬等因素相关。自噬是维持细胞器功能和细胞内营养环境的关键因素,也参与了系统的代谢稳态,这对于维持心脏功能和活性具有重要作用,其调节失调可能造成心肌细胞损伤。自噬相关信号通路包括m TOR信号通路及Beclin-1信号通路。糖尿病心肌病中自噬的影响因素包括高糖血症、游离脂肪酸过度积累、氧化应激、胰岛素抵抗、内质网应激等,该文就自噬相关通路在糖尿病心肌病发病机制中的研究进展进行综述。
Diabetic cardiomyopathy( DCM) is defined as coronary artery disease and hypertension in patients with diabetic myocardial dysfunction. The pathogenesis of DCM is reported to be related to inflammation,myocardial fibrosis,mitochondrial injury,myocardial cell apoptosis and autophagy. Autophagy is a key factor maintaining the function and nutrition environment of intracellular organelles,contributing to the steady metabolism of the system,which plays an important role in the maintenance of heart function and activities,while its adjustment disorders may cause myocardial cell injury. Autophagy-related signaling pathways include mT OR signaling pathway and Beclin-1 signaling pathway; factors influencing autophagy in DCM include hyperglycemia,excessive accumulation of free fatty acids,oxidative stress,insulin resistance,endoplasmic reticulum stress,etc.This paper reviews the progress of autophagy in the pathogenesis of DCM.
Diabetic cardiomyopathy( DCM) is defined as coronary artery disease and hypertension in patients with diabetic myocardial dysfunction. The pathogenesis of DCM is reported to be related to inflammation,myocardial fibrosis,mitochondrial injury,myocardial cell apoptosis and autophagy. Autophagy is a key factor maintaining the function and nutrition environment of intracellular organelles,contributing to the steady metabolism of the system,which plays an important role in the maintenance of heart function and activities,while its adjustment disorders may cause myocardial cell injury. Autophagy-related signaling pathways include mT OR signaling pathway and Beclin-1 signaling pathway; factors influencing autophagy in DCM include hyperglycemia,excessive accumulation of free fatty acids,oxidative stress,insulin resistance,endoplasmic reticulum stress,etc.This paper reviews the progress of autophagy in the pathogenesis of DCM.
引文
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[21]Zhang Y F,Meng N N,Li H Z,et al.Effect of naringin on oxidative stress and endoplasmic reticulum stress in diabetic cardiomyopathy[J].Chin J Chin Mater Med,2018,43(3):596-602.
[22]Zhang N,Cao M M,Liu H,et al.Autophagy regulates insulin resistance following endoplasmic reticulum stress in diabetes.[J].JPhysiol Biochem,2015,71(2):319-27.
[2]Kobayashi S,Liang Q.Autophagy and mitophagy in diabetic cardiomyopathy[J].Biochim Biophys Acta,2015,1852(2):252-61.
[3]Shirakabe A,Ikeda Y,Sciarretta S,et al.Aging and autophagy in the heart[J].Circ Res,2016,118(10):1563-76.
[4]Saito T,Asai K,Sato S,et al.Autophagic vacuoles in cardiomyocytes of dilated cardiomyopathy with initially decompensated heart failure predict improved prognosis[J].Autophagy,2016,12(3):579-87.
[5]杜慧雪,姜海宇,胡莹莹,等.白藜芦醇通过上调SIRT1促进自噬抑制2型糖尿病心肌病[J].中国新药杂志,2017,26(24):2970-7.[5]Du H X,Jiang H Y,Hu Y Y,et al.Resveratrol attenuates type 2diabetes-induced cardiomyopathy through promoting autophagy by up-regulating SIRT1[J].Chin J New Drugs,2017,26(24):2970-7.
[6]Yang F,Zhang L,Gao Z,et al.Exogenous H2S protects against diabetic cardiomyopathy by activating autophagy via the AMPK/m TOR pathway[J].Cell Physiol Biochem,2017,43(3):1168-87.
[7]Glover K,Li Y,Mukhopadhyay S,et al.Structural transitions in conserved,ordered Beclin 1 domains essential to regulating autophagy.[J].J Biol Chem,2017,292(39):16235-48.
[8]Zhu H,He L.Beclin 1 biology and its role in heart disease[J].Curr Cardiol Rev,2015,11(3):229-37.
[9]Hu X,Bai T,Xu Z,et al.Pathophysiological fundamentals of diabetic cardiomyopathy.[J].Compr Physiol,2017,7(2):693-711.
[10]Varga Z V,Giricz Z,Liaudet L,et al.Interplay of oxidative,nitrosative/nitrative stress,inflammation,cell death and autophagy in diabetic cardiomyopathy[J].Biochim Biophys Acta,2015,1852(2):232-42.
[11]Li Y,Zong W X,Ding W X.Recycling the danger via lipid droplet biogenesis after autophagy[J].Autophagy,2017,13(11):1995-7.
[12]李彩蓉,甘受益,黄红霞,等.二苯乙烯苷对糖尿病大鼠心肌损伤的保护作用[J].中国药理学通报,2016,32(3):410-5.[12]Li C R,Gan S Y,Huang H X,et al.Protective effects of tetrahydroxystilbene glucoside on cardiac dysfunction in experimental diabetic cardiomyopathy[J].Chin Pharmacol Bull,2016,32(3):410-5.
[13]Nguyen T B,Louie S M,Daniele J R,et al.DGAT1-dependent lipid droplet biogenesis protects mitochondrial function during starvation-induced autophagy[J].Dev Cell,2017,42(1):9-21.
[14]郭福团,许雄伟,潘建峰,等.桑枝多糖对糖尿病肾病小鼠肾皮质氧化应激作用的影响[J].中国药理学通报,2016,32(8):1148-52.[14]Guo F T,Xu X W,Pan J F,et al.Protective effects of NDP on LPSinduced neuron injuries in rat mixed cultures[J].Chin Pharmacol Bull,2016,32(8):1148-52.
[15]Wang J P,Chi R F,Wang K,et al.Oxidative stress impairs myocyte autophagy,resulting in myocyte hypertrophy[J].Exp Physiol,2018,103(4):461-72.
[16]Kang Y H,Cho M H,Kim J Y,et al.Impaired macrophage autophagy induces systemic insulin resistance in obesity[J].Oncotarget,2016,7(24):35577-91.
[17]Xin Z,Ma Z,Jiang S,et al.FOXOs in the impaired heart:new therapeutic targets for cardiac diseases[J].Biochim Biophys Acta,2016,863(2):486.
[18]刘春蕾,王莉莉,何昆仑.糖尿病心肌病与自噬[J].中华病理学杂志,2015,44(2):146-9.[18]Liu C L,Wang L L,He K L.Diabetic cardiomyopathy and autophagy[J].Chin J Pathol,2015,44(2):146-9.
[19]Yang L,Zhao D,Ren J,et al.Endoplasmic reticulum stress and protein quality control in diabetic cardiomyopathy[J].Biochim Biophys Acta,2015,1852(2):209-18.
[20]丰梅,付凌玲,张伟华,等.内质网应激调控细胞自噬和凋亡[J].中国细胞生物学学报,2018,40(3):455-62.[20]Feng M,Fu L L,Zhang W H,et al.Endoplasmic reticulum stress regulates cell autophagy and apoptosis[J].Chin J Cell Biol,2018,40(3):455-62.
[21]Zhang Y F,Meng N N,Li H Z,et al.Effect of naringin on oxidative stress and endoplasmic reticulum stress in diabetic cardiomyopathy[J].Chin J Chin Mater Med,2018,43(3):596-602.
[22]Zhang N,Cao M M,Liu H,et al.Autophagy regulates insulin resistance following endoplasmic reticulum stress in diabetes.[J].JPhysiol Biochem,2015,71(2):319-27.