幼年肥胖大鼠血管内皮细胞和其他代谢异常与炎症因子的关系

幼年肥胖大鼠血管内皮细胞及其他代谢异常与炎症因子的关系

摘要

研究背景、目的和意义：儿童肥胖及肥胖相关慢性疾病已成为一个主要的公共卫生问题。肥胖可以使多种慢性代谢性疾病的发病率升高，包括胰岛素抵抗、糖尿病、脂质代谢紊乱、高血压和动脉粥样硬化，共同组成了代谢综合症。中心性肥胖儿童腹腔内脏异位分布的病态脂肪组织分泌大量IL-1、IL-6和CRP。IL-1及IL-6与血管内皮功能损伤和亚临床炎症有密切的关系。本课题拟通过给予三周龄断乳期SD大鼠高脂饮食诱导肥胖幼鼠，测定血清炎症因子(CRP、IL-6)、内皮舒张因子和观察肥胖大鼠血管的病理变化，同时测定空腹血糖、空腹胰岛素及脂质代谢指标，探讨幼年肥胖大鼠内皮功能损伤的发生发展机制，为干预肥胖儿童的提供理论依据。

研究方法：18只断乳期SD雄性大鼠随机分为正常对照组和肥胖组(DIO 组)。对照组采用普通饲料，DIO组采用高脂高能饲料，喂养12周。实验中定时监测体重，喂养12周后在麻醉状态下采血、取睾周、肾周和肠系膜脂肪，留取肝脏及腹主动脉标本；测定体格、糖脂代谢指标、肝脏病理学改变、血管病理学改变和血清NO(硝酸还原酶法)；

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ELISA(Enzyme-Linked Immunosorbnent Assay)法测定相关细胞因子。

研究结果：高脂饲料喂养12周后，DIO组的各项体格指标（体重、体脂含量、Lee’s指数）、空腹血糖、胰岛素、甘油三酯、细胞因子高于对照组（P<0.05或P<0.01），高密度脂蛋白与NO低于对照组（P<0.01），总胆固醇和低密度脂蛋白无显著性差异。肝脏病理学改变为脂肪肝，血管无明显的病理学变化。肥胖大鼠存在糖脂代谢紊乱，脂肪细胞分泌的CRP、IL-6炎症因子与糖脂代谢指标有相关性（P<0.05或P<0.01），炎症因子在肥胖发病过程中起重要作用。

结论： 1. 高脂饮食诱导幼年大鼠肥胖，肥胖组大鼠出现糖脂代谢紊乱、脂肪肝等。

2. 肥胖组NO分泌量减少，且肥胖组炎症因子高于对照组，血

管无明显病理学变化。

3. 炎症因子可能是导致肥胖大鼠代谢异常的机制之一。

关键词：肥胖，幼年大鼠，血管，内皮细胞功能，炎症因子

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RELATIONSHIP AMONG V ASCULAR ENDOTHELIAL CELL ，OTHER METABOLIC DISORDERS AND INFLAMMATORY FACTORS

IN OBESE YOUNG RATS

ABSTRACT

Introduction： Obese children and obesity-related chronic diseases have become major public health issues. Obesity can make a variety of chronic metabolic diseases, increased morbidity, including insulin resistance, diabetes, dyslipidemia, hypertension and atherosclerosis, a common component of the metabolic syndrome. Obese children , particularly “central or abdominal” obesity, usually involving increased visceral fat, leads to an imbalanced production of adipocytokines(cytokines),such as IL-1(interleukin-1)、IL-6(interleukin-6) and C reactive protein（CRP）. IL-1 and IL-6 have a close relationship with vascular endothelial dysfunction and subclinical inflammation .In this study，we made attempts to show the mechanisms that

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the development of vascular endothelial dysfunction in diet-induced young obese Sprague-Dawleyrats rat. Serum inflammatory factors, CRP, endothelium relaxing factors(NO) ,fasting plasma glucose,serum lipids were tested.

Methods: 18 weaning male Sprague-Dawley rats were divides 2 groups: control group,dietery induced obesity group(DIO).The two groups were respectively fed by normal chow, a high-fat diet.After 12 weeks,blood and adipose tissue were harvested from the two group rats.Biomarkers of obesity, CRP, endothelium relaxing factors(NO) ,fasting plasma glucose, serum lipids were tested, Serum inflammatory factors were detected by Enzyme-Linked Immunosorbnent Assay. liver and vascular were also detected by the way of pathological observation.

Results: After 12 weeks, the levels of lee index, fat wet weight, CRP, IL-6, triglyceride,fasting blood glucose and plasma insulin in DIO group were higher than those in control group (P <0.05 or P <0.01), while NO and high-density lipoprotein were significantly lower than in control group (P <0.01). There were no differences in the levels of total cholesterol and low density lipoprotein between groups. Liver fatty degeneration existed in obese rats, However, the abdominal aorta had no pathobiology change. Glycolipid metabolism disorders existed in obese rats. CRP, IL-6 and other

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