西格列汀对肥胖合并非酒精性脂肪肝大鼠的代谢调节作用及机制的探讨

发布时间：2018-12-30 16:27

【摘要】：目的:背景:随着社会经济发展以及生活水平不断提高生活方式的转变,人们日常餐饮中摄入更高的热量,且静坐的生活方式越来越普遍,从而导致体内能量过剩、脂肪堆积。肥胖症是指体内脂肪堆积过多和(或)分布异常、体重增加,是遗传因素、环境因素等多种因素相互作用所引起的慢性代谢性疾病。超重和肥胖在全球流行,已经成为严峻的公共卫生危机之一。肥胖症作为代谢综合征的主要组分之一,与多种疾病如2型糖尿病、血脂异常、高血压、冠心病、卒中、肿瘤等密切相关。过多的脂肪沉积在内脏器官,则造成内脏器官的脂肪样变,最常见的为肝脏脂肪样变,称之为脂肪肝。脂肪样变的肝细胞在凝血因子及白蛋白的合成方面、毒素降解、胆红素的循环等生命活动中重要代谢过程不能顺利进行,进而引发一系列代谢疾病的发生和发展。因此本文拟初步探讨西格列汀对肥胖合并非酒精性脂肪肝大鼠糖脂代谢及氧化应激的影响。方法:将实验SD大鼠随机分为正常饮食组(ND组)、高脂饮食组,高热量高脂饮食喂养高脂饮食组大鼠16周,成功构建肥胖合并非酒精性脂肪肝模型;随机将高脂饮食组大鼠等量分至肥胖对照组(OB组)、西格列汀干预组(ST组),以上三组每组各8只。16周后西格列汀干预组大鼠予西格列汀10 mg/(kg·d)干预6周,正常饮食组及肥胖对照组予等量生理盐水干预6周。测定各组实验大鼠干预前后空腹血糖(FPG)、空腹血清胰岛素(FINS)、血清甘油三酯(TG)及氧化应激指标血清超氧化物歧化酶(SOD)、血清丙二醛(MDA)、血清谷胱甘肽过氧化物酶(GSH-Px)的水平及干预后10%肝脏组织匀浆氧化应激指标GSH-Px、SOD、MDA及TG水平,同时计算胰岛素抵抗指数(HOMA-IR);油红O染色观察肝脏组织病理切片脂肪样变程度。结果:1).干预前,OB组与ST组大鼠各指标无统计学差异(P0.05);OB组、ST组与ND组比较各指标有统计学差异,ND组FPG、FINS、TG、MDA水平较低(P0.05),血清SOD、GSH-Px水平较高(P0.05)。2).干预后,ST组与ND组比较,ST组肝脏组织TG及MDA浓度升高(P0.05),FPG、FINS、血清TG、HOMA-IR、血清MDA、血清及肝脏组织中SOD、GSH-Px浓度差异无统计学意义(P0.05),肝脏脂肪变样的程度升高;与OB组比较,ST组FPG、FINS、HOMA-IR、血清及肝脏组织MDA、TG浓度降低,血清及肝脏组织中GSH-Px、SOD浓度升高,差异具有统计学意义(P0.05),肝脏脂肪样变的程度降低。结论:西格列汀可调节肥胖合并非酒精性脂肪肝大鼠的糖代谢和脂代谢,并降低肝脏脂肪样变程度,可能是通过调节氧化应激反应来实现上述调节。
[Abstract]:Objective: with the development of social economy and the change of living style, people eat more calories in their daily meals, and the life style of sit-ins is more and more common, which leads to excess energy and fat accumulation in the body. Obesity is a chronic metabolic disease caused by excessive fat accumulation and / or abnormal distribution and weight gain in the body. It is a chronic metabolic disease caused by the interaction of genetic factors, environmental factors and other factors. Overweight and obesity have become one of the severe public health crises in the world. As one of the main components of metabolic syndrome, obesity is closely related to many diseases such as type 2 diabetes, dyslipidemia, hypertension, coronary heart disease, stroke, tumor and so on. Too much fat deposits in the visceral organs, causing the visceral organs, the most common fatty liver, called fatty liver. The important metabolic processes such as coagulation factor and albumin synthesis, toxin degradation and bilirubin circulation in lipopolysaccharide hepatocytes can not be carried out smoothly, which leads to the occurrence and development of a series of metabolic diseases. Therefore, the effect of siglitatin on glucose and lipid metabolism and oxidative stress in obese rats with non-alcoholic fatty liver was studied. Methods: the experimental SD rats were randomly divided into normal diet group (ND group), high-fat diet group, high-calorie high-fat diet group and high-fat diet group for 16 weeks. The rats in high-fat diet group were randomly divided into obese control group (OB group) and siglitatin intervention group (ST group). Normal diet group and obese control group were treated with saline for 6 weeks. Fasting blood glucose (FPG), fasting serum insulin (FINS), serum triglyceride (TG) and serum superoxide dismutase (SOD), serum malondialdehyde (MDA), were measured before and after intervention in each group of experimental rats. The level of serum glutathione peroxidase (GSH-Px) and the levels of GSH-Px,SOD,MDA and TG in 10% liver homogenate after intervention were calculated, and insulin resistance index (HOMA-IR) was calculated. Oil red O staining was used to observe the degree of fatty degeneration in pathological sections of liver. Results: 1). Before intervention, there was no statistical difference between OB group and ST group (P0.05). In OB group, ST group and ND group, the FPG,FINS,TG,MDA level was lower (P0.05) and the serum SOD,GSH-Px level was higher (P0.05). After intervention, the concentrations of TG and MDA in liver tissue of ST group were higher than those in ND group (P0.05), but there was no significant difference in FPG,FINS, serum TG,HOMA-IR, serum MDA, serum and liver tissue SOD,GSH-Px concentration (P0.05). The degree of liver fat variant was increased. Compared with OB group, the concentration of MDA,TG in serum and liver of ST group was decreased, the concentration of GSH-Px,SOD in serum and liver tissue was increased, the difference was statistically significant (P0.05), and the degree of hepatic fatty degeneration was decreased. Conclusion: siglitatin can regulate the metabolism of glucose and lipid in obese rats with non-alcoholic fatty liver and decrease the degree of hepatic fatty degeneration, which may be achieved by regulating the oxidative stress reaction.
【学位授予单位】：安徽医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R575;R589.2

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