Fenofibrate Therapy Restores Antioxidant Protection and Improves Myocardial Insulin Resistance in a Rat Model of Metabolic Syndrome and Myocardial Ischemia: The Role of Angiotensin II.
Fenofibrate Therapy Restores Antioxidant Protection and Improves Myocardial Insulin Resistance in a Rat Model of Metabolic Syndrome and Myocardial Ischemia: The Role of Angiotensin II.
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DOI：
10.3390/molecules22010031
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发表时间：
2016-12-28
期刊：
影响因子：
--
通讯作者：
Rubio-Ruiz ME
中科院分区：
文献类型：
--
作者：
Ibarra-Lara L;Sánchez-Aguilar M;Sánchez-Mendoza A;Del Valle-Mondragón L;Soria-Castro E;Carreón-Torres E;Díaz-Díaz E;Vázquez-Meza H;Guarner-Lans V;Rubio-Ruiz ME
肾素-血管紧张素系统（RAS）激活促进氧化应激，增加代谢综合征（MetS）心功能障碍的风险，并促进局部胰岛素抵抗。贝特类调节RAS，改善代谢综合征、2型糖尿病和心血管疾病。本研究旨在探讨非诺贝特对心肌缺血大鼠心肌血管紧张素Ⅱ（Ang Ⅱ）/血管紧张素Ⅱ 1型受体（AT 1）信号通路的影响及其与氧化应激和心肌胰岛素抵抗的关系。将对照和MetS大鼠分配到以下组：（a）假手术组;（B）媒介物治疗的心肌梗死（MI）（MI-V）;和（c）非诺贝特治疗的心肌梗死（MI-F）。用非诺贝特治疗显著降低MetS动物中的甘油三酯、非高密度脂蛋白胆固醇（非HDL-C）、胰岛素水平和胰岛素抵抗指数（HOMA-IR）。MetS和MI增加了Ang II浓度和AT 1表达，有利于心肌氧化应激（高水平的丙二醛，烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶4（NOX 4）的过表达，降低的总抗氧化能力和减少的超氧化物歧化酶（SOD）1、SOD 2和过氧化氢酶的表达）和抑制胰岛素信号级联的表达：磷脂酰肌醇3-激酶（PI 3 K）/蛋白激酶B（Pk B，也称为Akt）/Glut-4/内皮型一氧化氮合酶（eNOS）。总之，非诺贝特治疗有利于抗氧化剂环境的结果，减少血管紧张素II/AT 1/NOX 4信号通路，重建心脏胰岛素信号通路。这可能会优化心脏代谢，改善心肌缺血时的血管舒张功能。
Renin-angiotensin system (RAS) activation promotes oxidative stress which increases the risk of cardiac dysfunction in metabolic syndrome (MetS) and favors local insulin resistance. Fibrates regulate RAS improving MetS, type-2 diabetes and cardiovascular diseases. We studied the effect of fenofibrate treatment on the myocardic signaling pathway of Angiotensin II (Ang II)/Angiotensin II type 1 receptor (AT1) and its relationship with oxidative stress and myocardial insulin resistance in MetS rats under heart ischemia. Control and MetS rats were assigned to the following groups: (a) sham; (b) vehicle-treated myocardial infarction (MI) (MI-V); and (c) fenofibrate-treated myocardial infarction (MI-F). Treatment with fenofibrate significantly reduced triglycerides, non-high density lipoprotein cholesterol (non-HDL-C), insulin levels and insulin resistance index (HOMA-IR) in MetS animals. MetS and MI increased Ang II concentration and AT1 expression, favored myocardial oxidative stress (high levels of malondialdehyde, overexpression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (NOX4), decreased total antioxidant capacity and diminished expression of superoxide dismutase (SOD)1, SOD2 and catalase) and inhibited expression of the insulin signaling cascade: phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PkB, also known as Akt)/Glut-4/endothelial nitric oxide synthase (eNOS). In conclusion, fenofibrate treatment favors an antioxidant environment as a consequence of a reduction of the Ang II/AT1/NOX4 signaling pathway, reestablishing the cardiac insulin signaling pathway. This might optimize cardiac metabolism and improve the vasodilator function during myocardial ischemia.
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直接证据表明心肌缺血后的心肌胰岛素抵抗导致缺血后心力衰竭。
影响因子：
4.6
作者：
Fu F;Zhao K;Li J;Xu J;Zhang Y;Liu C;Yang W;Gao C;Li J;Zhang H;Li Y;Cui Q;Wang H;Tao L;Wang J;Quon MJ;Gao F
通讯作者：
Gao F
影响因子：
20.1
作者：
Beauloye, C;Bertrand, L;Hue, L
通讯作者：
Hue, L
影响因子：
3
作者：
Ibarra-Lara, Luz;Sanchez-Aguilar, Maria;Sanchez-Mendoza, Alicia
通讯作者：
Sanchez-Mendoza, Alicia
影响因子：
3
作者：
Ibarra-Lara, Luz;Hong, Enrique;Sanchez-Mendoza, Alicia
通讯作者：
Sanchez-Mendoza, Alicia
DOI：
10.1016/j.jtcvs.2010.08.003
发表时间：
2010-11-01
影响因子：
6
作者：
Amorim, Paulo A.;Nguyen, T. Dung;Doenst, Torsten
通讯作者：
Doenst, Torsten