Leptin、Ghrelin对阻塞性睡眠呼吸暂停低通气综合征的影响

发布时间：2018-11-06 17:46

【摘要】：目的本文将探讨Leptin、Ghrelin对阻塞性睡眠呼吸暂停低通气综合征(Obstractive Sleep Apnea Hypopnea Symptom OSAHS)的影响。首先通过观察高脂饮食对大鼠血中Leptin、Ghrelin的浓度变化及其受体分布表达的影响,阐明它们在肥胖大鼠形成过程中的作用；然后通过观察在间歇性缺氧状态下肥胖大鼠血中Leptn、Ghrelin的变化,揭示两者在OSAHS发病过程中的作用。阻塞性睡眠呼吸暂停低通气综合征是一种全身性疾病,是许多疾病的共同病理基础,近年来其发病率不断升高,危害性大,现有临床治疗手段均有弊端,故从发病机制上研究OSAHS的发生、发展,为临床诊断和治疗OSAHS提供新的作用靶点有重大意义。方法选购体重约160g±10g雄性幼年健康SD大鼠58只,先适应性喂养一周后随机分为2组,即正常对照组(基础饲料喂养,n=28)和肥胖诱导组(高脂饲料+普通饲料混合喂养,n=30),每周记录体重、体长,再将对照组和高脂组大鼠根据是否低氧各分为2组,常氧组每组12只,低氧组每组16只,按要求给予低氧干预,在第4周末和第8周末从各组随机取6只大鼠,分别留取血、肺及脂肪组织标本,用酶联免疫法检测血浆Leptin、 Ghrelin含量,用RT-PCR、Western-Blot方法检测Leptin、Ghrelin受体、蛋白在脂肪组织、肺组织中的表达差异。结果ELISA结果表明,血浆中Leptin、Ghrelin浓度在肥胖、低氧和时间三种因素的影响下表现不同的水平,单纯肥胖时,血清Leptin水平升高,Ghrelin水平下降(4周时P0.05,8周时P0.01)；间歇性缺氧4周末血清中Leptin含量减少,Ghrelin分泌增加(P0.05)；间歇性缺氧8周末,Leptin水平进一步升高,血浆Ghrelin水平也明显增高(P0.05)。RT-PCR、 Western-Blot结果则不同,Leptin受体及蛋白在脂肪组织中的表达水平与血浆中浓度变化呈现一致,肺组织中无意义；而Ghrelin受体和蛋白在肺及脂肪组织中均未检出有意义的结果。结论血浆中Leptin、Ghrelin的水平与肥胖和低氧的干预密切相关,表明其与肥胖、阻塞性睡眠呼吸暂停低通气综合征的发生及发展程度的关系；Leptin受体及蛋白在脂肪组织中的表达进一步证实了这一结果；而未检出结果则表明相关组织中该因子的表达量太少或者不表达,可以提示以后的研究方向。
[Abstract]:Objective to investigate the effect of Leptin,Ghrelin on (Obstractive Sleep Apnea Hypopnea Symptom OSAHS) in obstructive sleep apnea hypopnea syndrome (OSAS). Firstly, the effects of high-fat diet on the changes of Leptin,Ghrelin concentration and the expression of Leptin,Ghrelin receptor in the blood of obese rats were observed to elucidate their role in the formation of obese rats. Then, by observing the changes of Leptn,Ghrelin in the blood of obese rats under intermittent hypoxia, the role of both in the pathogenesis of OSAHS was revealed. Obstructive sleep apnea hypopnea syndrome is a systemic disease, which is the common pathological basis of many diseases. In recent years, the incidence of obstructive sleep apnea hypopnea syndrome is increasing and harmful. Therefore, it is of great significance to study the occurrence and development of OSAHS from its pathogenesis, and to provide a new target for clinical diagnosis and treatment of OSAHS. Methods 58 male healthy SD rats, weighing about 160 g 卤10 g, were randomly divided into two groups: normal control group (basic diet, nong28) and obesity induction group (high fat diet, normal diet, n = 30). The rats in the control group and the hyperlipidemia group were divided into 2 groups according to whether they were hypoxic or not, 12 rats in the normoxic group and 16 rats in the hypoxic group. At the end of the 4th and 8th weeks, 6 rats were randomly selected from each group. Blood, lung and adipose tissue samples were collected respectively. The plasma Leptin, Ghrelin content was detected by enzyme-linked immunosorbent assay (Elisa), and the Leptin,Ghrelin receptor was detected by RT-PCR,Western-Blot method. Protein expression in adipose tissue and lung tissue is different. Results the results of ELISA showed that the concentration of Leptin,Ghrelin in plasma showed different levels under the influence of three factors: obesity, hypoxia and time. The level of serum Leptin increased and the level of Ghrelin decreased in simple obesity group (P0.05, P0.01 at week 4). After 4 weeks of intermittent hypoxia, the content of Leptin in serum decreased and the secretion of Ghrelin increased (P0.05). At the end of 8 weeks of intermittent hypoxia, the level of Leptin increased further and the level of plasma Ghrelin increased significantly (P0.05). The expression of Leptin receptor and protein in adipose tissue was consistent with the change of plasma concentration, and the expression of Leptin receptor and protein in adipose tissue was different from that of RT-PCR, Western-Blot. There was no significance in lung tissue. Ghrelin receptors and proteins were not detected in lung and adipose tissues. Conclusion the level of Leptin,Ghrelin in plasma is closely related to the intervention of obesity and hypoxia, which indicates that it is related to the occurrence and development of obesity and obstructive sleep apnea hypopnea syndrome. The expression of Leptin receptor and protein in adipose tissue further confirmed this result, but the undetected result indicated that the expression of Leptin receptor and protein in the related tissues was too little or not, which could indicate the future research direction.
【学位授予单位】：桂林医学院
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R766

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