中枢nesfatin-1通过交感神经调节外周脂肪代谢

发布时间：2018-03-31 22:18

本文选题：Nesfatin-1　切入点：2型糖尿病　出处：《青岛大学》2015年硕士论文

【摘要】：目的:研究中枢nesfatin-1对糖尿病小鼠外周脂肪动代谢调节作用;同时,通过药物阻断交感神经对白色脂肪组织和骨骼肌的支配,探究中枢nesfatin-1参与外周脂肪代谢调节的分子机制。方法:将实验小鼠给予高脂饮食和2次小剂量链脲佐菌素(STZ)诱导成为2型糖尿病小鼠,然后进行侧脑室置管术。根据侧脑室注射药物不同设生理盐水对照组和nesfatin-1实验组两大组,每组中枢给药前30min分别腹腔给予α受体阻断剂组(酚妥拉明)、β受体阻断剂(普萘洛尔)和生理盐水。监测中枢给药1小时内每组血糖变化,检测血浆中胰岛素含量和游离脂肪酸(FFA)水平;分别使用Real Time PCR法和Western Blot法从基因和蛋白水平分别检测各组白色脂肪组织中脂肪动员相关酶类(HSL、ATGL)和骨骼肌组织中脂肪酸β氧化相关酶类(AMPK-ACC-CPT1)的变化。结果:中枢nesfatin-1对外周血糖没有显著影响;与生理盐水组比较,中枢注射nesfatin-1组血浆游离脂肪酸显著降低(p0.05),给予β受体阻断剂后,游离脂肪酸水平升高(p0.05);Nesfatin-1组脂肪动员相关酶类p-HSL和ATGL的蛋白和基因水平都显著升高(p0.05),而给予β受体阻断剂普萘洛尔后,HSL和ATGL的基因水平显著下降(p0.05),p-HSL蛋白水平明显下降(p0.05);Nesfatin-1实验组与生理盐水对照组比较,骨骼肌脂肪酸β氧化相关酶类(AMPK、ACC)磷酸化蛋白和基因水平表达升高(p0.05),提前给予α阻断剂酚妥拉明后,其蛋白和基因水平表达都明显下降(p0.05)。结论:中枢注射nesfatin-1通过交感神经调节外周脂肪动员和脂肪酸β氧化。
[Abstract]:Objective: To study the central nesfatin-1 on diabetic peripheral fat metabolism dynamic regulation; at the same time, the drugs block the sympathetic innervation of white adipose tissue and skeletal muscle, to explore the molecular mechanisms involved in the central nesfatin-1 peripheral fat metabolism regulation. Methods: the mice were fed a high-fat diet and 2 small dose of STZ (STZ) - induced into type 2 diabetic mice, then lateral ventricle catheterization. According to intracerebroventricular injection of different drugs with normal saline control group and nesfatin-1 experimental group two groups, each group of the central administration before 30min were given abdominal cavity alpha blocker group (phentolamine), beta blockers (propranolol) and saline. Monitoring the central administration changes within 1 hours with blood glucose, plasma insulin determination and free fatty acid (FFA) level; Time PCR respectively using Real method and Western Blot method and gene from Protein levels were measured in each group of white adipose tissue fat mobilization related enzymes (HSL, ATGL) and enzymes related to fatty acid oxidation in skeletal muscle tissues (AMPK-ACC-CPT1). Results: the changes of central nesfatin-1 peripheral blood glucose had no significant effect; compared with the normal saline group, intracerebroventricular injection of nesfatin-1 group significantly decreased plasma free fatty acids (P0.05), given beta blockers, elevated levels of free fatty acids (P0.05); the level of gene and protein in Nesfatin-1 group and ATGL p-HSL fat mobilization related enzymes are significantly increased (P0.05), and to the beta blocker propranolol, gene level of HSL and ATGL decreased significantly (P0.05), p-HSL protein level (P0.05) Nesfatin-1 decreased significantly; the experimental group compared with saline control group, skeletal muscle fatty acid oxidation related enzymes (AMPK, ACC) phosphorylation of protein and gene expression level increased (P0.05), to advance After the administration of phentolamine, the expression level of protein and gene decreased significantly (P0.05). Conclusion: central injection of nesfatin-1 can regulate peripheral fat mobilization and fatty acid beta oxidation through sympathetic nerve.

【学位授予单位】：青岛大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R587.1;R589.2

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