有氧运动预防2型糖尿病中对大鼠铁代谢的影响

发布时间：2018-02-27 12:19

  本文关键词： 铁过载 2型糖尿病 氧化应激 一氧化氮 铁调素　出处：《河北师范大学》2015年硕士论文　论文类型：学位论文

【摘要】：人体和动物模型的研究均表明机体铁超载是糖尿病发病的危险因素。亚铁离子是助氧化剂,催化细胞反应,导致活性氧产生,增加氧化应激水平,引起组织损伤。流行病学研究发现,2型糖尿病(T2DM)患者血清铁蛋白(SF)含量明显高于非T2DM人群。SF浓度与血清胰岛素、血糖、高血压、血脂异常及肥胖程度呈正相关。有氧运动可显著增加机体供能物质代谢水平,目前广泛应用于T2DM等代谢性疾病的预防和治疗。有氧运动是否会通过调控机体铁动态平衡而防治T2DM,目前尚不清楚。本研究主要探讨有氧运动在T2DM发病过程中,对大鼠铁代谢和胰岛素抵抗的改善作用,以及相关铁代谢调控因子铁调素与一氧化氮含量的变化。阐明有氧运动通过调控机体铁代谢而防治T2DM发生的机制,为早期预防和治疗T2DM提供理论依据。研究内容与方法:24只12月龄SD大鼠,随机分为对照组(C组)、高糖高脂膳食组(H组)、高糖高脂膳食结合有氧运动组(HE组),每组8只。C组进行基础饲料喂养,其余两组使用高糖高脂饲料,高糖高脂饲料配方为猪油10%、蔗糖20%、蛋黄粉8%、胆酸钠0.1%、基础饲料61.9%(AIN-93G),河北省动物实验中心制作提供。高糖高脂饲料中矿物质铁含量与基础饲料相同(含铁100 mg/kg)。HE组在2W适应运动后,进行15m/min、45min/d、坡度5、6d/w、3W有氧运动干预,其余两组安静喂养。5周后,用酶联免疫吸附实验(Elisa)检测SF、血清胰岛素、肝脏八羟基脱氧鸟苷;逆转录-聚合酶链反应(RT-PCR)测量肝脏Hepcidin m RNA含量;生化试剂盒检测血清铁、血清总铁结合力、肝组织铁、血糖、高密度脂蛋白、总胆固醇、肝超氧化物歧化酶(SOD)、肝丙二醛(MDA)、肝过氧化氢酶(CAT)、血清一氧化氮(NO)、肝脏NO、肝脏胆碱酯酶、血常规;肝组织切片用苏木精-伊红(HE)染色。研究结果:(1)5周高糖高脂膳食诱导H组大鼠血糖升高,罹患T2DM。各组大鼠5周后体重均有所增加,H组较C组和HE组体重增加更为显著(P0.01)。(2)各组大鼠糖脂代谢状态:H组和HE组胰岛素抵抗指数、血清胰岛素、血糖均高于C组(P0.01,P0.05),HE组胰岛素抵抗指数、血清胰岛素、血糖显著低于H组(P0.01)。H组和HE组胰岛素敏感指数均低于C组(P0.01),HE组胰岛素敏感指数显著高于H组(P0.01)。H组低密度脂蛋白含量显著高于C组,HE组低密度脂蛋白含量显著低于H组(P0.01)。HE组和C组高密度脂蛋白含量均高于H组(P0.01,P0.05)。(3)各组大鼠机体铁状态变化:H组血清铁、转铁蛋白饱和度、肝组织铁显著高于C组和HE组(P0.01,P0.05);H组和HE组SF均显著高于C组(P0.01),HE组SF显著低于H组(P0.01)。线性回归分析显示血糖和血清铁蛋白呈线性正相关。(4)各组大鼠氧化应激与肝细胞损伤程度:H组肝SOD、肝CAT显著低于C组和HE组(P0.01,P0.05),HE组和C组MDA显著低于H组(P0.01)。H组白细胞含量显著高于C组(P0.01),HE组白细胞含量低于H组(P0.05)。H组和HE组血红蛋白浓度显著低于C组(P0.01,P0.05)。(5)各组大鼠肝脏组织形态学改变:H组肝细胞混合性大、小泡脂变,大泡脂变脂滴大,核偏移,且小灶状炎症细胞浸润,少数细胞凋亡,核固缩。HE组少量肝细胞小泡性脂肪变,细胞核居中,胞质内充满微小脂滴。与H组肝细胞相较,HE组肝脂肪变较轻,且无炎症细胞浸润和细胞凋亡。(6)铁代谢调控因子表达量变化:H组Hepcidin m RNA显著高于C组(P0.05),HE组Hepcidin m RNA显著低于H组(P0.01)。H组血清NO和肝脏NO含量显著高于C组,HE组血清NO和肝脏NO含量显著低于H组(P0.01)。结论:(1)长期高糖高脂饮食诱导大鼠体重增加,加重铁过载和氧化应激,出现胰岛素抵抗。实验结果表明,通过对自然衰老大鼠进行高糖高脂饲料喂养,大鼠血糖超过11.1mmol/L,2型糖尿病造模成功。(2)有氧运动降低机体铁储存,增加抗氧化应激酶的活性,缓解氧化应激与胰岛素抵抗,减轻高脂膳食大鼠肝组织脂肪样变,预防2型糖尿病的发生。(3)长期有氧运动通过降低大鼠的NO和Hepcidin含量,控制炎症反应,促进肝铁释放,缓解铁过载,稳定铁状态。适度运动能够降低大鼠体内对高糖高脂饲料刺激产生过量的NO和Hepcidin,并维持在正常的生理范围内。
[Abstract]:The study of human and animal models indicate that body iron overload is a risk factor for the onset of diabetes. The ferrous ion is co oxidant, catalytic reaction cell, resulting in the generation of reactive oxygen species, increase the level of oxidative stress, causing damage to tissue. Epidemiological studies have found that type 2 diabetes mellitus (T2DM) patients with serum ferritin (SF) was significantly higher than that of non T2DM in.SF concentration and serum insulin, blood glucose, hypertension, dyslipidemia and obesity was positively related to the degree. Aerobic exercise can significantly increase the body energy metabolism level, prevention and treatment has been widely used in T2DM and other metabolic diseases. Aerobic exercise is through regulation of iron homeostasis and control of T2DM, it is not clear. This study focused on the aerobic exercise in the pathogenesis of T2DM, to improve the role of iron metabolism and insulin resistance in rats, as well as related to iron metabolism regulation of hepcidin and a factor The changes of nitric oxide content. The aerobic exercise regulation of iron metabolism and prevent the occurrence of T2DM through the mechanism, to provide theoretical basis for early prevention and treatment of T2DM. The research contents and methods: 24 12 month old SD rats were randomly divided into control group (C group), high-fat diet group (H group), high glucose the high-fat diet combined with aerobic exercise group (HE group),.C group with 8 rats in each group were fed basic diet, the other two groups with high glucose and high fat diet, high-fat feed formula for lard 10%, 20% sucrose, 8% yolk powder, 0.1% sodium cholate, 61.9% basic feed (AIN-93G), Hebei province animal experiment center provide basis and content of iron minerals. High glucose and high fat diet in the same feed (FE 100 mg/kg) in the.HE group 2W adaptation after exercise, 15m/min, 45min/d, 5,6d/w, 3W grade, aerobic exercise intervention, the other two groups fed quiet after.5 weeks, using enzyme-linked immunosorbent assay (Elisa) detection of SF. Blood 娓呰儼宀涚礌,鑲濊剰鍏�缇熷熀鑴辨哀楦熻嫞�

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