Bhandari Uma, Kumar Vinay, Kumar Parveen, Tripathi C D, Khanna Geetika
Department of Pharmacology, Faculty of Pharmacy, Hamdard University, New Delhi, India.
Indian J Med Res. 2015 Nov;142(5):598-605. doi: 10.4103/0971-5916.171290.
BACKGROUND & OBJECTIVES: Cardiomyocyte apoptosis is one of the pathologic phenomena associated with diabetes and related conditions including obesity, insulin resistance and hyperlipidaemia. In the present study, the protective effects of pioglitazone on cardiomyocyte apoptosis was evaluated in experimental diabetes induced by low dose of streptozoticin (STZ) combined with high fat diet (HFD) in rats.
Male Wistar rats (150-200 g) were injected with low-dose STZ (45 mg/kg, i.v., single dose) and orally fed with a HFD (20 g/day/rat) for a period of 28 days and simultaneously treated with pioglitazone (20 mg/kg/p.o.) for a period of 21 days (from 8 th day to 28 th day). On 29 th day blood was collected, serum separated and used for biochemical parameters. Heart tissue was used for cardiomyocyte apoptosis measurement and also for histopathological examination.
Pioglitazone treatment resulted in a decrease in cardiomyocyte apoptosis as revealed by a decrease in cardiac caspase-3, lactate dehydrogenase (LDH) levels and DNA fragmentation, and an increase in Na+K+ATPase levels in diabetic rats. Cardiac histology of diabetic control rats showed dense focal fatty infiltration in the myocardial cells whereas normal architecture with regular morphology and well preserved cytoplasm was observed with pioglitazone treatment. Pioglitazone treatment significantly reduced the heart rate, mean arterial blood pressure, body mass index (BMI) and levels of serum glucose, leptin, insulin, HOMA-IR, total cholesterol (TC) and triglycerides (TGs), apoliproprotein-B glycosylated haemoglobin (HbA1c) levels and atherogenic index, and increased the levels of serum high density lipoprotein cholesterol (HDL-C) and cardiac antioxidant enzymes.
INTERPRETATION & CONCLUSIONS: The present study results suggest that pioglitazone possesses cardiac anti-apoptotic potential in diabetic rat model and can be further explored for its use for treatment of diabetic cardiomyopathy.
心肌细胞凋亡是与糖尿病及包括肥胖、胰岛素抵抗和高脂血症在内的相关病症有关的病理现象之一。在本研究中，在低剂量链脲佐菌素（STZ）联合高脂饮食（HFD）诱导的实验性糖尿病大鼠中评估了吡格列酮对心肌细胞凋亡的保护作用。
雄性Wistar大鼠（150 - 200克）静脉注射低剂量STZ（45毫克/千克，单剂量），并口服高脂饮食（20克/天/大鼠）持续28天，同时用吡格列酮（20毫克/千克/口服）治疗21天（从第8天至第28天）。在第29天采集血液，分离血清并用于生化参数检测。心脏组织用于心肌细胞凋亡检测以及组织病理学检查。
吡格列酮治疗导致糖尿病大鼠心肌细胞凋亡减少，表现为心脏半胱天冬酶 - 3、乳酸脱氢酶（LDH）水平降低以及DNA片段化减少，同时钠钾ATP酶水平升高。糖尿病对照大鼠的心脏组织学显示心肌细胞有密集的局灶性脂肪浸润，而吡格列酮治疗组观察到形态正常、结构规则且细胞质保存良好的正常结构。吡格列酮治疗显著降低了心率、平均动脉血压、体重指数（BMI）以及血清葡萄糖、瘦素、胰岛素、HOMA - IR、总胆固醇（TC）和甘油三酯（TGs）、载脂蛋白B糖化血红蛋白（HbA1c）水平和动脉粥样硬化指数，并提高了血清高密度脂蛋白胆固醇（HDL - C）水平和心脏抗氧化酶水平。
本研究结果表明，吡格列酮在糖尿病大鼠模型中具有心脏抗凋亡潜力，可进一步探索其用于治疗糖尿病心肌病的用途。
