Rosa C M, Gimenes R, Campos D H S, Guirado G N, Gimenes C, Fernandes A A H, Cicogna A C, Queiroz R M, Falcão-Pires I, Miranda-Silva D, Rodrigues P, Laurindo F R, Fernandes D C, Correa C R, Okoshi M P, Okoshi K
Department of Internal Medicine, Botucatu Medical School, Sao Paulo State University-UNESP, Botucatu, Sao Paulo, Brazil.
Sagrado Coração University-USC, Bauru, Sao Paulo, Brazil.
Cardiovasc Diabetol. 2016 Sep 1;15(1):126. doi: 10.1186/s12933-016-0442-1.
Although increased oxidative stress is a major component of diabetic hypertensive cardiomyopathy, research into the effects of antioxidants on cardiac remodeling remains scarce. The actions of antioxidant apocynin include inhibiting reactive oxygen species (ROS) generation by nicotinamide adenine dinucleotide phosphate (NADPH) oxidases and ROS scavenging. We evaluated the effects of apocynin on cardiac remodeling in spontaneously hypertensive rats (SHR) with diabetes mellitus (DM).
Male SHR were divided into four groups: control (SHR, n = 16); SHR treated with apocynin (SHR-APO; 16 mg/kg/day, added to drinking water; n = 16); diabetic SHR (SHR-DM, n = 13); and SHR-DM treated with apocynin (SHR-DM-APO, n = 14), for eight weeks. DM was induced by streptozotocin (40 mg/kg, single dose). Statistical analyzes: ANOVA and Tukey or Mann-Whitney.
Echocardiogram in diabetic groups showed higher left ventricular and left atrium diameters indexed for body weight, and higher isovolumetric relaxation time than normoglycemic rats; systolic function did not differ between groups. Isolated papillary muscle showed impaired contractile and relaxation function in diabetic groups. Developed tension was lower in SHR-APO than SHR. Myocardial hydroxyproline concentration was higher in SHR-DM than SHR, interstitial collagen fraction was higher in SHR-DM-APO than SHR-APO, and type III collagen protein expression was lower in SHR-DM and SHR-DM-APO than their controls. Type I collagen and lysyl oxidase expression did not differ between groups. Apocynin did not change collagen tissue. Myocardial lipid hydroperoxide concentration was higher in SHR-DM than SHR and SHR-DM-APO. Glutathione peroxidase activity was lower and catalase higher in SHR-DM than SHR. Apocynin attenuated antioxidant enzyme activity changes in SHR-DM-APO. Advanced glycation end-products and NADPH oxidase activity did not differ between groups.
Apocynin reduces oxidative stress independently of NADPH oxidase activity and does not change ventricular or myocardial function in spontaneously hypertensive rats with diabetes mellitus. The apocynin-induced myocardial functional impairment in SHR shows that apocynin actions need to be clarified during sustained chronic pressure overload.
尽管氧化应激增加是糖尿病性高血压性心肌病的主要组成部分，但关于抗氧化剂对心脏重塑影响的研究仍然很少。抗氧化剂白杨素的作用包括抑制烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶产生活性氧（ROS）以及清除ROS。我们评估了白杨素对患有糖尿病（DM）的自发性高血压大鼠（SHR）心脏重塑的影响。
将雄性SHR分为四组：对照组（SHR，n = 16）；用白杨素治疗的SHR（SHR-APO；16 mg/kg/天，添加到饮用水中；n = 16）；糖尿病性SHR（SHR-DM，n = 13）；以及用白杨素治疗的SHR-DM（SHR-DM-APO，n = 14），持续八周。通过链脲佐菌素（40 mg/kg，单次剂量）诱导DM。统计分析：方差分析和Tukey检验或Mann-Whitney检验。
糖尿病组的超声心动图显示，与血糖正常的大鼠相比，以体重为指标的左心室和左心房直径更大，等容舒张时间更长；各组之间的收缩功能没有差异。离体乳头肌显示糖尿病组的收缩和舒张功能受损。SHR-APO的舒张张力低于SHR。SHR-DM的心肌羟脯氨酸浓度高于SHR，SHR-DM-APO的间质胶原分数高于SHR-APO，SHR-DM和SHR-DM-APO的III型胶原蛋白表达低于其对照组。各组之间I型胶原蛋白和赖氨酰氧化酶的表达没有差异。白杨素没有改变胶原组织。SHR-DM的心肌脂质过氧化产物浓度高于SHR和SHR-DM-APO。SHR-DM的谷胱甘肽过氧化物酶活性低于SHR，而过氧化氢酶活性高于SHR。白杨素减弱了SHR-DM-APO中抗氧化酶活性的变化。各组之间晚期糖基化终产物和NADPH氧化酶活性没有差异。
白杨素可独立于NADPH氧化酶活性降低氧化应激，并且不会改变患有糖尿病的自发性高血压大鼠的心室或心肌功能。白杨素诱导的SHR心肌功能损害表明，在持续的慢性压力过载期间，白杨素的作用需要进一步阐明。
