Viana Gonçalves Igor Cândido, Cerdeira Cláudio Daniel, Poletti Camara Eduardo, Dias Garcia José Antônio, Ribeiro Pereira Lima Brigagão Maísa, Bessa Veloso Silva Roberta, Bitencourt Dos Santos Gérsika
Faculdade de Medicina, Universidade José do Rosário Vellano (UNIFENAS), Alfenas, MG, Brazil.
Departamento de Bioquímica (DBq), Instituto de Ciências Biomédicas, Universidade Federal de Alfenas (UNIFAL-MG), Alfenas, MG, Brazil.
Rev Port Cardiol. 2017 Sep;36(9):629-638. doi: 10.1016/j.repc.2017.02.014. Epub 2017 Aug 18.
Dyslipidemia is associated with increased risk of cardiovascular disease and atherosclerosis, and hence with high morbidity and mortality. This study investigated the effects of the nitroxide 4-hydroxy-2,2,6,6-tetramethylpiperidine 1-oxyl (Tempol) on lipid profile and cardiac morphology in low-density lipoprotein (LDL) receptor gene knockout (LDLr-/-) mice.
Male LDLr-/- mice (three months old, approximately 22 g weight) were divided into the following groups: controls, including (1) standard chow (SC, n=8) and (2) high-fat diet (HFD, n=8); and treatment, including (3) standard chow + Tempol (SC+T, n=8) (30 mg/kg administered by gavage, once daily) and (4) high-fat diet + Tempol (HFD+T, n=8) (30 mg/kg). After 30 days of the diet/treatment, whole blood was collected for analysis of biochemical parameters (total cholesterol, triglycerides [TG], high-density lipoprotein [HDL], LDL, and very low-density lipoprotein [VLDL]). The heart was removed through thoracotomy and histological analysis of the left ventricle was performed.
A significant increase in TG, LDL, and VLDL and marked left ventricular hypertrophy (LVH) were demonstrated in the HFD group relative to the SC group (p<0.05), while Tempol treatment (HFD+T group) significantly (p<0.05) prevented increases in the levels of these lipid profile markers and attenuated LVH compared with the HFD group.
In this study, Tempol showed potential for the prevention of events related to serious diseases of the cardiovascular system.
血脂异常与心血管疾病及动脉粥样硬化风险增加相关，进而导致高发病率和死亡率。本研究调查了氮氧化物4-羟基-2,2,6,6-四甲基哌啶1-氧基（Tempol）对低密度脂蛋白（LDL）受体基因敲除（LDLr-/-）小鼠血脂谱和心脏形态的影响。
雄性LDLr-/-小鼠（3个月大，体重约22克）分为以下几组：对照组，包括（1）标准饲料（SC，n = 8）和（2）高脂饮食（HFD，n = 8）；治疗组，包括（3）标准饲料+Tempol（SC+T，n = 8）（通过灌胃给药，30毫克/千克，每日一次）和（4）高脂饮食+Tempol（HFD+T，n = 8）（30毫克/千克）。饮食/治疗30天后，采集全血分析生化参数（总胆固醇、甘油三酯[TG]、高密度脂蛋白[HDL]、低密度脂蛋白和极低密度脂蛋白[VLDL]）。通过开胸取出心脏，对左心室进行组织学分析。
与SC组相比，HFD组的TG、LDL和VLDL显著升高，左心室肥厚（LVH）明显（p<0.05），而Tempol治疗（HFD+T组）与HFD组相比，显著（p<0.05）阻止了这些血脂谱标志物水平的升高，并减轻了LVH。
在本研究中，Tempol显示出预防与心血管系统严重疾病相关事件的潜力。
