年龄、肥胖及糖尿病对胰岛素样生长因子结合蛋白2在脂肪组织中表达的影响

发布时间：2018-01-02 09:19

本文关键词：年龄、肥胖及糖尿病对胰岛素样生长因子结合蛋白2在脂肪组织中表达的影响　出处：《吉林大学》2016年硕士论文　论文类型：学位论文

【摘要】：目的:肥胖是一种复杂的、由多种因素共同作用导致的慢性非传染性疾病。肥胖可以导致体内多种代谢紊乱而增加许多疾病的患病风险,大量流行病学调查显示肥胖人群比正常人群更容易出现葡萄糖耐量减低和胰岛素抵抗。目前研究发现,衰老、肥胖和胰岛素抵抗是共存的。而胰岛素样生长因子结合蛋白2(IGFBP2)作为由白色脂肪组织分泌的脂肪因子,可以有效预防高脂饮食诱导的肥胖及年龄相关性胰岛素抵抗的发生与发展。但是,IGFBP2在发生胰岛素抵抗的组织中的表达情况尚不明确。因此,此项研究的目的在于明确IGFBP2在内脏白色脂肪组织的表达情况是否受到肥胖、胰岛素抵抗及衰老的调控,及其与血液循环中IGFBP2浓度的关系。材料与方法:全部小鼠均选取雄性,分别选取4月龄、12月龄和24月龄的C57BL6小鼠各12只;4月龄ob/ob,db/db和野生型小鼠各6只;4月龄高糖高脂饮食诱导的肥胖小鼠(HFD-ob)及正常饮食对照的C57BL6小鼠各6只。全部小鼠禁食8小时后断颈处死,并立即留取其血液(心脏穿刺)和内脏白色脂肪组织及皮下白色脂肪组织,分别使用离心后冷藏及直接液氮冷藏的方式存储标本。脂肪组织提取RNA,反转录为c DNA进行real-time PCR检测m IGFBP2的表达情况,并通过ELISA试剂盒对相应小鼠IGFBP2的血浆水平进行测定。使用方差分析、t检验及单因素相关性回归分析进行数据统计,所有数据使用SPSS17版本软件进行分析,P0.05认为有统计学意义。结果:(1)年龄对IGFBP2在脂肪组织中表达的影响:研究发现非肥胖小鼠组,与4月龄的小鼠比较,12月龄和24月龄小鼠的内脏白色脂肪组织中IGFBP2 m RNA的表达明显减少(P0.05),而在皮下脂肪组织无明显差别;(2)肥胖和糖尿病对IGFBP2在脂肪组织表达的影响:与同为4月龄的正常饮食小鼠组比较,HFD-ob小鼠内脏脂肪组织IGFBP2 m RNA表达水平显著降低,与野生型小鼠相比,ob/ob、db/db小鼠内脏脂肪组织IGFBP2 m RNA表达水平显著降低,而IGFBP2在皮下脂肪组织中的表达不受肥胖和糖尿病的影响,此差异在皮下脂肪组织未获得;(3)IGFBP2在上述小鼠血液中的检测结果与其在内脏白色脂肪组织中的表达情况呈现高度一致性。结论:IGFBP2的基因转录调节具有组织特异性,其在内脏白色脂肪组织及血液循环中的表达受年龄、肥胖及糖代谢异常的影响,且具有高度一致性。这一结果暗示年龄和糖脂代谢异常对调控IGFBP2的表达具有重要的作用。
[Abstract]:Objective: obesity is a complex chronic non-communicable disease caused by multiple factors. Obesity can lead to multiple metabolic disorders in the body and increase the risk of many diseases. A large number of epidemiological studies have shown that obese people are more likely than normal to develop impaired glucose tolerance and insulin resistance. Obesity and insulin resistance coexist, and insulin-like growth factor-binding protein 2IGFBP2is a fatty factor secreted by white adipose tissue. It can effectively prevent the occurrence and development of obesity and age-related insulin resistance induced by high fat diet. However, the expression of IGFBP2 in insulin-resistant tissues is not clear. The aim of this study was to determine whether the expression of IGFBP2 in visceral white adipose tissue is regulated by obesity, insulin resistance, and aging. Materials and methods: all the male mice were selected, 12 C57BL6 mice of 4 months old and 24 months old C57BL6 mice were selected. Each of the 4 month old ob-obo db- db and wild-type mice was composed of 6 mice and 6 wild-type mice. Four months old high-sugar high-fat diet induced obesity mice (HFD-ob) and normal diet control C57BL6 mice each 6. All the mice were killed after 8 hours fasting. The blood (heart puncture), visceral white adipose tissue and subcutaneous white adipose tissue were collected immediately and stored in centrifugation and direct liquid nitrogen storage respectively. RNA was extracted from adipose tissue. The expression of m IGFBP2 was detected by real-time PCR with c DNA reverse transcription. The plasma level of mouse IGFBP2 was measured by ELISA kit, and the data were analyzed by ANOVA t test and single factor correlation regression analysis. All data is analyzed using SPSS17 version software. Results the effect of age on the expression of IGFBP2 in adipose tissue: the study found that the non-obese mice group was compared with the 4-month-old mice. The expression of IGFBP2 m RNA in white adipose tissue of mice aged 12 months and 24 months decreased significantly, but there was no significant difference in subcutaneous adipose tissue. (2) the effect of obesity and diabetes on the expression of IGFBP2 in adipose tissue: compared with normal diet mice of 4 months of age. The expression of IGFBP2 m RNA in visceral adipose tissue of HFD-ob mice was significantly lower than that in wild type mice. The expression of IGFBP2 m RNA in visceral adipose tissue of db/db mice was significantly decreased, while the expression of IGFBP2 in subcutaneous adipose tissue was not affected by obesity and diabetes. This difference was not obtained in subcutaneous adipose tissue. 3). The results of IGFBP2 in the blood of the above mice were highly consistent with their expression in visceral white adipose tissue. Conclusion the gene transcriptional regulation of 1: IGFBP2 has tissue specificity. Its expression in visceral white adipose tissue and blood circulation is affected by age, obesity and abnormal glucose metabolism. These results suggest that age and abnormal glucose and lipid metabolism play an important role in regulating the expression of IGFBP2.
【学位授予单位】：吉林大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R589.2;R587.1

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