Clinical Pharmacology Department, Faculty of Medicine, Alexandria University, Alexandria, Egypt.
J Cardiovasc Pharmacol Ther. 2010 Jun;15(2):175-81. doi: 10.1177/1074248409356557. Epub 2010 Feb 4.
The aim of the current study was to address the issue of cardiomyocyte apoptosis as a possible contributor in the development of diabetic cardiomyopathy and whether it would be possible to suppress this apoptosis by the use of a peroxisome proliferator-activated receptor (PPAR)-alpha agonist (fenofibrate) or a PPAR-gamma agonist (rosiglitazone).
Ten normal male albino rats (group I) were injected intraperitoneally (IP) by a single dose of saline and served as a control for group II. Thirty male albino rats were made diabetic by IP streptozotocin (STZ) injection and were divided into 3 groups: group II (nontreated diabetic rats), groups III and IV (diabetic rats treated with PPAR-gamma agonist (rosiglitazone), and PPAR-alpha agonist (fenofibrate) respectively, for 12 weeks starting 1 week following STZ injection.
The studied drugs decreased left ventricular to body weight ratio and cardiac: caspase-3, tumor necrosis factor-alpha, hydroxyproline, free fatty acids (FFAs) as well as triglycerides (TGs) and improved oxidative stress parameters as well as left ventricular papillary muscle developed tension (DT).
The results of the current study support the hypothesis that apoptosis plays a key role in the pathophysiology of diabetic cardiomyopathy and demonstrate that the use of PPAR-alpha and -gamma agonists might have a protective role against diabetic cardiomyopathy.
本研究旨在探讨心肌细胞凋亡是否可能导致糖尿病心肌病的发生，并探讨过氧化物酶体增殖物激活受体（PPAR）-α激动剂（非诺贝特）或 PPAR-γ激动剂（罗格列酮）是否可能抑制这种凋亡。
10 只正常雄性白化大鼠（I 组）经腹腔单次注射生理盐水，作为 II 组的对照。30 只雄性白化大鼠经腹腔注射链脲佐菌素（STZ）诱导糖尿病，并分为 3 组：II 组（未治疗的糖尿病大鼠）、III 组和 IV 组（分别用 PPAR-γ激动剂（罗格列酮）和 PPAR-α激动剂（非诺贝特）治疗的糖尿病大鼠，自 STZ 注射后 1 周开始治疗 12 周。
研究药物降低了左心室与体重比以及心脏：半胱天冬酶-3、肿瘤坏死因子-α、羟脯氨酸、游离脂肪酸（FFAs）以及三酰甘油（TGs），改善了氧化应激参数以及左心室乳头肌的发展张力（DT）。
本研究结果支持凋亡在糖尿病心肌病病理生理学中起关键作用的假说，并表明 PPAR-α和 -γ激动剂的使用可能对糖尿病心肌病具有保护作用。
