發(fā)布時(shí)間：2018-03-31 22:18

  本文選題：Nesfatin-1　切入點(diǎn)：2型糖尿病　出處：《青島大學(xué)》2015年碩士論文

【摘要】：目的:研究中樞nesfatin-1對(duì)糖尿病小鼠外周脂肪動(dòng)代謝調(diào)節(jié)作用;同時(shí),通過藥物阻斷交感神經(jīng)對(duì)白色脂肪組織和骨骼肌的支配,探究中樞nesfatin-1參與外周脂肪代謝調(diào)節(jié)的分子機(jī)制。方法:將實(shí)驗(yàn)小鼠給予高脂飲食和2次小劑量鏈脲佐菌素(STZ)誘導(dǎo)成為2型糖尿病小鼠,然后進(jìn)行側(cè)腦室置管術(shù)。根據(jù)側(cè)腦室注射藥物不同設(shè)生理鹽水對(duì)照組和nesfatin-1實(shí)驗(yàn)組兩大組,每組中樞給藥前30min分別腹腔給予α受體阻斷劑組(酚妥拉明)、β受體阻斷劑(普萘洛爾)和生理鹽水。監(jiān)測(cè)中樞給藥1小時(shí)內(nèi)每組血糖變化,檢測(cè)血漿中胰島素含量和游離脂肪酸(FFA)水平;分別使用Real Time PCR法和Western Blot法從基因和蛋白水平分別檢測(cè)各組白色脂肪組織中脂肪動(dòng)員相關(guān)酶類(HSL、ATGL)和骨骼肌組織中脂肪酸β氧化相關(guān)酶類(AMPK-ACC-CPT1)的變化。結(jié)果:中樞nesfatin-1對(duì)外周血糖沒有顯著影響;與生理鹽水組比較,中樞注射nesfatin-1組血漿游離脂肪酸顯著降低(p0.05),給予β受體阻斷劑后,游離脂肪酸水平升高(p0.05);Nesfatin-1組脂肪動(dòng)員相關(guān)酶類p-HSL和ATGL的蛋白和基因水平都顯著升高(p0.05),而給予β受體阻斷劑普萘洛爾后,HSL和ATGL的基因水平顯著下降(p0.05),p-HSL蛋白水平明顯下降(p0.05);Nesfatin-1實(shí)驗(yàn)組與生理鹽水對(duì)照組比較,骨骼肌脂肪酸β氧化相關(guān)酶類(AMPK、ACC)磷酸化蛋白和基因水平表達(dá)升高(p0.05),提前給予α阻斷劑酚妥拉明后,其蛋白和基因水平表達(dá)都明顯下降(p0.05)。結(jié)論:中樞注射nesfatin-1通過交感神經(jīng)調(diào)節(jié)外周脂肪動(dòng)員和脂肪酸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.

【學(xué)位授予單位】：青島大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2015
【分類號(hào)】：R587.1;R589.2

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本文編號(hào)：1692715