Departments of Biomedical Sciences, Faculty of Health Sciences, University of Stellenbosch, Tygerberg, South Africa.
Cardiovasc Drugs Ther. 2012 Jun;26(3):205-16. doi: 10.1007/s10557-012-6377-1.
By increasing circulating free fatty acids and the rate of fatty acid oxidation, obesity decreases glucose oxidation and myocardial tolerance to ischemia. Partial inhibition of fatty acid oxidation may improve myocardial tolerance to ischemia/reperfusion (I/R) in obesity. We assessed the effects of oxfenicine treatment on post ischemic cardiac function and myocardial infarct size in obese rats.
Male Wistar rats were fed a control diet or a high calorie diet which resulted in diet induced obesity (DIO) for 16 weeks. Oxfenicine (200 mg/kg/day) was administered to control and DIO rats for the last 8 weeks. Isolated hearts were perfused and infarct size and post ischemic cardiac function was assessed after regional or global ischemia and reperfusion. Cardiac mitochondrial function was assessed and myocardial expression and activity of CPT-1 (carnitine palmitoyl transferase-1) and IRS-1 (insulin receptor substrate-1) was assessed using Western blot analysis.
In the DIO rats, chronic oxfenicine treatment improved post ischemic cardiac function and reduced myocardial infarct size after I/R but had no effect on the cardiac mitochondrial respiration. Chronic oxfenicine treatment worsened post ischemic cardiac function, myocardial infarct size and basal mitochondrial respiration in control rat hearts. Basal respiratory control index (RCI) values, state 2 and state 4 respiration rates and ADP phosphorylation rates were compromised by oxfenicine treatment.
Chronic oxfenicine treatment improved myocardial tolerance to I/R in the obese rat hearts but decreased myocardial tolerance to I/R in control rat hearts. This decreased tolerance to ischemia of oxfenicine treated controls was associated with adverse changes in basal and reoxygenation mitochondrial function. These changes were absent in oxfenicine treated hearts from obese rats.
肥胖通过增加循环游离脂肪酸和脂肪酸氧化率，减少葡萄糖氧化和心肌对缺血的耐受性。部分抑制脂肪酸氧化可能会改善肥胖患者心肌对缺血/再灌注（I/R）的耐受性。我们评估了奥芬尼辛治疗对肥胖大鼠缺血后心功能和心肌梗死面积的影响。
雄性 Wistar 大鼠给予对照饮食或高热量饮食，导致饮食诱导肥胖（DIO）16 周。奥芬尼辛（200mg/kg/天）在最后 8 周内给予对照和 DIO 大鼠。分离心脏进行灌注，并在区域性或全球性缺血和再灌注后评估梗死面积和缺血后心功能。使用 Western blot 分析评估心脏线粒体功能以及心肌 CPT-1（肉毒碱棕榈酰转移酶-1）和 IRS-1（胰岛素受体底物-1）的表达和活性。
在 DIO 大鼠中，慢性奥芬尼辛治疗改善了缺血后心功能，并减少了 I/R 后的心肌梗死面积，但对心脏线粒体呼吸没有影响。慢性奥芬尼辛治疗恶化了对照大鼠心脏的缺血后心功能、心肌梗死面积和基础线粒体呼吸。基础呼吸控制指数（RCI）值、状态 2 和状态 4 呼吸率以及 ADP 磷酸化率受到奥芬尼辛处理的损害。
慢性奥芬尼辛治疗改善了肥胖大鼠心脏的 I/R 耐受性，但降低了对照大鼠心脏的 I/R 耐受性。奥芬尼辛处理对照大鼠缺血耐受性的降低与基础和再氧化线粒体功能的不良变化有关。这些变化在肥胖大鼠的奥芬尼辛治疗心脏中不存在。
