Wang Guoguang, Li Wei, Lu Xiaohua, Zhao Xue
Department of Pathophysiology, Wannan Medical College, Wuhu, China.
Heart Int. 2011 Sep 29;6(2):e21. doi: 10.4081/hi.2011.e21. Epub 2011 Nov 22.
Heart failure (HF) is a common and serious comorbidity of diabetes. Oxidative stress has been associated with the pathogenesis of chronic diabetic complications including cardiomyopathy. The ability of antioxidants to inhibit injury has raised the possibility of new therapeutic treatment for diabetic heart diseases. Riboflavin constitutes an essential nutrient for humans and animals and it is an important food additive. Riboflavin, a precursor of flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), enhances the oxidative folding and subsequent secretion of proteins. The objective of this study was to investigate the cardioprotective effect of riboflavin in diabetic rats. Diabetes was induced in 30 rats by a single injection of streptozotocin (STZ) (70 mg /kg). Riboflavin (20 mg/kg) was orally administered to animals immediately after induction of diabetes and was continued for eight weeks. Rats were examined for diabetic cardiomyopathy by left ventricular (LV) remadynamic function. Myocardial oxidative stress was assessed by measuring the activity of superoxide dismutase (SOD), the level of malondialdehyde (MDA) as well as heme oxygenase-1 (HO-1) protein level. Myocardial connective tissue growth factor (CTGF) level was measured by Western blot in all rats at the end of the study. In the untreated diabetic rats, left ventricular systolic pressure (LVSP) rate of pressure rose (+dp/dt), and rate of pressure decay (-dp/dt) were depressed while left ventricular end-diastolic pressure (LVEDP) was increased, which indicated the reduced left ventricular contractility and slowing of left ventricular relaxation. The level of SOD decreased, CTGF and HO-1 protein expression and MDA content rose. Riboflavin treatment significantly improved left ventricular systolic and diastolic function in diabetic rats, there were persistent increases in significant activation of SOD and the level of HO-1 protein, and a decrease in the level of CTGF. These results suggest that riboflavin treatment ameliorates myocardial function and improves heart oxidant status, whereas raising myocardial HO-1 and decreasing myocardial CTGF levels have beneficial effects on diabetic cardiomyopathy.
心力衰竭（HF）是糖尿病常见且严重的合并症。氧化应激与包括心肌病在内的慢性糖尿病并发症的发病机制有关。抗氧化剂抑制损伤的能力为糖尿病性心脏病的新治疗方法带来了可能性。核黄素是人和动物必需的营养素，也是一种重要的食品添加剂。核黄素是黄素单核苷酸（FMN）和黄素腺嘌呤二核苷酸（FAD）的前体，可增强蛋白质的氧化折叠及后续分泌。本研究的目的是探讨核黄素对糖尿病大鼠的心脏保护作用。通过单次注射链脲佐菌素（STZ）（70 mg/kg）诱导30只大鼠患糖尿病。糖尿病诱导后立即给动物口服核黄素（20 mg/kg），并持续八周。通过左心室（LV）血流动力学功能检查大鼠是否患有糖尿病性心肌病。通过测量超氧化物歧化酶（SOD）活性、丙二醛（MDA）水平以及血红素加氧酶-1（HO-1）蛋白水平来评估心肌氧化应激。在研究结束时，通过蛋白质印迹法测量所有大鼠的心肌结缔组织生长因子（CTGF）水平。在未治疗的糖尿病大鼠中，左心室收缩压（LVSP）、压力上升速率（+dp/dt）和压力衰减速率（-dp/dt）降低，而左心室舒张末期压力（LVEDP）升高，这表明左心室收缩力降低和左心室舒张减慢。SOD水平降低，CTGF和HO-1蛋白表达以及MDA含量升高。核黄素治疗显著改善了糖尿病大鼠的左心室收缩和舒张功能，SOD的显著激活和HO-1蛋白水平持续升高，CTGF水平降低。这些结果表明，核黄素治疗可改善心肌功能并改善心脏氧化状态，而提高心肌HO-1水平和降低心肌CTGF水平对糖尿病性心肌病具有有益作用。
