Downregulation of Peroxisme Proliferator Activated Receptor Gamma Co-Activator 1.ALPHA. in Diabetic Rats Role of Pharmacomodulation:Role of Pharmacomodulation
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概要
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Diabetes mellitus (DM), which induces alterations in energy metabolism, is the leading cause of cardiovascular disease. We postulated that peroxisome proliferator activated receptor-γ coactivator 1α (PGC-α), a transcriptional coactivator that is the primary regulator of oxidative metabolism and mitochondrial biogenesis, and cardiac function are depressive in DM and simvastatin and losartan therapy can improve the affects of DM on mRNA expression of PGC-1α and cardiac function. An experimental model of DM (induced by streptozocin 60 mg/kg) in adult male rats (n = 24) was used to investigate the mRNA expression of PGC-1α in the left ventricular myocardium. These rats were divided into group I (insulin therapy only, n = 8), group II (insulin plus simvastatin 20 mg/kg/day orally, n = 8), and group III (insulin plus losartan 20 mg/kg/day orally, n = 8). Diabetic rats and 8 healthy rats (group IV) were sacrificed at 3 weeks following DM induction. The mRNA expression of PGC-1α was measured using real-time polymerase chain reaction (RT-PCR). Additionally, transthoracic echocardiography was performed on days 0 and 21. The experimental results indicated that the mRNA expression of PGC-1α and the left ventricular ejection fraction (LVEF %) were significantly lower in groups I, II and III than in group IV (all P < 0.001). However, the mRNA expression of PGC-1α and the LVEF were significantly higher in group III than in groups I and II (both P < 0.01). Conversely, mRNA expression of PGC-1α and LVEF did not differ between groups I and II (P > 0.5). In conclusion, DM induces suppression of mRNA expression of PGC-1α and LV function in diabetic rats. Losartan and not simvastatin therapy improved the LV function and the expression of this mitochondrial-biogenesis regulator.
- International Heart Journal刊行会の論文
著者
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Youssef Ali
Cardiology Department Suez Canal University Hospital
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Chang Li-teh
Basic Science Nursing Department Meiho Institute Of Technology
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Wu Chiung-jen
Division Of Cardiology Chang Gung Memorial Hospital-kaohsiung Medical Center Chang Gung University C
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Chua Sarah
Division Of Cardiology Chang Gung Memorial Hospital-kaohsiung Medical Center Chang Gung University C
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Yip Hon-kan
Division Of Cardiology Chang Gung Memorial Hospital-kaohsiung Medical Center Chang Gung University C
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Chua Sarah
Division of Cardiology, Chang Gung Memorial Hospital Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine
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Wang Chi-Young
Department of Life Science, National Pingtung University of Science and Technology
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Sun Cheuk-Kwan
Department of General Surgery, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine
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Sun Cheuk-Kwan
Department of General Surgery, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine
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