本文選題：GDF11　切入點：骨骼肌　出處：《重慶醫(yī)科大學(xué)》2017年碩士論文

【摘要】：目的:最近研究發(fā)現(xiàn)GDF11可使衰老骨骼肌、心肌及大腦年輕化。既往研究報道衰老的骨骼肌與胰島素抵抗密切相關(guān)。但GDF11是否具有改善胰島素抵抗的作用尚未見明確的報道。因此,本研究擬探討GDF11對骨骼肌胰島素抵抗的作用。方法:體內(nèi)實驗采用低脂飲食、高脂飲食喂養(yǎng)小鼠,設(shè)置對照組及建立肥胖伴有胰島素抵抗小鼠模型。IPGTT和ITT試驗分別檢測小鼠糖耐量和胰島素敏感性。ELISA法檢測小鼠血清GDF11水平,Western blotting和實時定量PCR分別檢測小鼠骨骼肌中GDF11蛋白和基因水平的表達。體外實驗采用棕櫚酸干預(yù)骨骼肌細胞建立體外胰島素抵抗模型。實時定量PCR檢測棕櫚酸干預(yù)后骨骼肌細胞GDF11基因水平的表達。體外采用GDF11干預(yù)棕櫚酸誘導(dǎo)的骨骼肌細胞,2NBDG實驗檢測細胞糖攝取,Western blotting和實時定量PCR檢測GLUT4,IRS-1及PGC-1α的表達。結(jié)果:(1)體內(nèi)實驗:與低脂喂養(yǎng)組相比,高脂喂養(yǎng)組小鼠體重明顯增加,糖耐量異常,胰島素敏感性降低(P0.05);與低脂喂養(yǎng)組比較,高脂喂養(yǎng)組小鼠血清中GDF11和骨骼肌中GDF11的表達均明顯降低(P0.05)。(2)體外實驗:與對照組相比,棕櫚酸干預(yù)后骨骼肌細胞GDF11的表達明顯降低,骨骼肌細胞糖攝取及糖攝取相關(guān)基因GLUT4和IRS-1的表達也明顯下降(P0.05);加入GDF11干預(yù)后,骨骼肌細胞糖攝取及GLUT4和IRS-1的表達無明顯變化(P0.05)。(3)與對照組相比,棕櫚酸干預(yù)后骨骼肌細胞PGC-1α表達明顯被抑制(P0.05);加GDF11干預(yù)后PGC-1α表達無明顯變化(P0.05)。結(jié)論:本研究首次發(fā)現(xiàn)在肥胖伴胰島素抵抗模型小鼠的血清和骨骼肌中GDF11蛋白明顯降低,在體外棕櫚酸干預(yù)骨骼肌細胞后GDF11表達也明顯減少。而GDF11干預(yù)棕櫚酸誘導(dǎo)的骨骼肌細胞,其胰島素抵抗沒有明顯改善。
[Abstract]:Objective: recent studies have found that GDF11 can make skeletal muscle aging. Myocardial and brain rejuvenation. Previous studies have reported that aging skeletal muscle is closely associated with insulin resistance. However, whether GDF11 can improve insulin resistance has not been clearly reported. The aim of this study was to investigate the effect of GDF11 on insulin resistance in skeletal muscle. Methods: mice were fed with low fat diet and high fat diet in vivo. Establishment of obese mice model with insulin resistance. IPGTT and ITT test were used to detect glucose tolerance, insulin sensitivity, Elisa and serum GDF11 level. Western blotting and real-time quantitative PCR were used to detect skeletal muscle, respectively. In vitro insulin resistance model was established by palmitic acid intervention in skeletal muscle cells. Real-time quantitative PCR was used to detect the expression of GDF11 gene in skeletal muscle cells after palmitic acid intervention. GDF11 was used to interfere with palmitic acid-induced skeletal muscle cell line 2NBDG to detect the expression of GLUT4, IRS-1 and PGC-1 偽, and to detect the expression of GLUT4, IRS-1 and PGC-1 偽 by real-time quantitative PCR. Results: compared with low fat feeding group, the expression of GLUT4, IRS-1 and PGC-1 偽 was detected by GDF11 in vivo. Compared with low fat feeding group, the expression of GDF11 in serum and GDF11 in skeletal muscle were significantly decreased in high fat feeding group (compared with control group): compared with control group, compared with control group, the expression of GDF11 in serum and GDF11 in skeletal muscle were significantly decreased in high fat feeding group (P < 0. 05, P 0. 05, P 0. 05, P 0. 05, P 0. 05, P 0. 05, P 0. 05, P 0. 05). After palmitic acid intervention, the expression of GDF11 in skeletal muscle cells was significantly decreased, and the expression of glucose uptake and glucose uptake related genes GLUT4 and IRS-1 in skeletal muscle cells was also significantly decreased after the addition of GDF11. There was no significant change in glucose uptake and the expression of GLUT4 and IRS-1 in skeletal muscle cells. The expression of PGC-1 偽 in skeletal muscle cells was significantly inhibited after palmitic acid intervention, but no significant change was found in PGC-1 偽 expression after GDF11 treatment. Conclusion: the expression of GDF11 protein in serum and skeletal muscle of obese mice with insulin resistance was significantly decreased in this study. After palmitic acid intervention in vitro, the expression of GDF11 in skeletal muscle cells was also significantly decreased, while GDF11 intervention in palmitic acid-induced skeletal muscle cells had no significant improvement in insulin resistance.
【學(xué)位授予單位】：重慶醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R587.1

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