8-羟基脱氧鸟苷在胰岛素抵抗大鼠骨骼肌的表达及运动、吡格列酮的干预作用

摘要

胰岛素抵抗(Insulin Resistance,IR)是许多内分泌代谢失调相关疾病的共同病理生理基础,现代社会长期高脂膳食和运动缺乏的生活方式,使其患病率明显增加.虽然对IR的研究十分活跃,但由于其发病机制十分复杂,迄今尚未完全阐明.近年的研究表明氧化应激是IR发生、发展的关键因素.8-羟基脱氧鸟苷(8-Hydroxy-2'-Deoxyguanosine,8-OHdG)是体内活性氧(Reactive Oxygen Species,ROS)引起DNA氧化损伤修饰产物之一,是国际上公认的一种新的评价DNA氧化损伤和氧化应激状态的敏感指标和生物标志物[1].目前国内外对氧化应激和IR关系的研究较多,但关于8-OHdG这一新型氧化应激指标与IR的关系研究尚少,尤其运动对这一指标的影响国内尚未见报道.故本实验以高糖高脂饲料诱导IR模型大鼠为对象,观察8-OHdG在IR大鼠骨骼肌的表达,探讨氧化应激指标8-OHdG和IR的关系,并观察运动、吡格列酮的干预作用.%Objective: To observe the expression of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in skeletal muscle of insulin resistant (IR), rats and the intervention of exercise and pioglitazone. Method: A total of 40 male Wistar rats were randomly divided into control group (w = 10) and model group (M, n = 30), fed with normal diet and high sugar high fat diet, respectively. Eight weeks later, the model group was randomly divided into IR group (IR, n= 10) , exercise group (E, n=10) and pioglitazone group (Pio, n= 10). The three groups were continually fed with high sugar and high fat diet, while the exercise group was administered with swimming training and the pioglitazone group was given a daily dose of 20mg/kg/d pioglitazone for eight weeks in addition at the same time. At the end of sixteen weeks, the body wight of rats was measured. Rats blood sample for measuring the levels of glucose (FPG) and insulin (FINS). The indexes of IR (HOMA-IR) were calculated. Xanthinoxidase method was applied to detect the activity of superoxide dismutase (SOD) in skeletal muscle. Immunohistochemistry method was applied to detect the expression levels of 8-OHdG in skeletal muscle. Results: (l)The levels of FPG, FINS,HOMA-IR in serum and the expression levels of 8-OHdG in skeletal muscle in IR group were higher than those in control and the activity of SOD in skeletal muscle were lower, after the intervention of exercise/ pioligtazone, SOD activity were increased, the others parameters were decreased. (2)In a Bivariate analysis, HOMA-IR were correlated with the expression levels of 8-OHdG in skeletal muscle positively, the activity of SOD in skeletal muscle were correlated with HOMA-IR negatively. Conclusion: Exercise/pioglitazone could inhibit oxidative stress in skeletal muscle of IR group rats and improve IR.