Vaspin对高脂喂养大鼠胰岛素抵抗的影响及机制研究
发布时间：2018-10-31 11:23
【摘要】：目的:1、探讨Vaspin能否改善高脂喂养大鼠的胰岛素抵抗;2、探讨Vaspin是否通过作用于肝脏的IRS/PI3K/Akt及NF-κB信号通路,进而改善高脂喂养大鼠的胰岛素抵抗。方法:30只8周龄雄性SD大鼠,适应性喂养一周后,随机分为正常组(NC组,n=10)和模型组(n=20)。正常组喂以正常饲料,模型组以高脂饲料喂养16周建立胰岛素抵抗模型。胰岛素抵抗大鼠随机分为高脂组(HFD组,n=10)和320ng/ml Vaspin干预组(HFD+Vaspin组,n=10)。HFD+Vaspin组经腹腔注射Vaspin蛋白溶液,每日1次,共干预8周,NC组和HFD组分别给予相应体积的生理盐水。干预结束后称重并留取血标本,检测血清中空腹血糖(FBG)、空腹胰岛素(FINS)、甘油三酯(TG)、总胆固醇(TC)、肿瘤坏死因子-α(TNF-α)、白介素-6(IL-6)的水平,行口服葡萄糖耐量试验(OGTT)和胰岛素耐受性试验(ITT)评估大鼠糖耐量及胰岛素耐受性,行高胰岛素-正葡萄糖钳夹试验评估外周组织胰岛素敏感性的变化。分离大鼠肝脏组织,采用Western blot、RT-PCR检测大鼠肝脏IRS/PI3K/Akt、NF-κB信号通路及下游炎性因子的表达水平。结果:Vaspin干预后,血清FBG、FINS、TNF-α、IL-6浓度显著降低(P0.05),而体重、TG、TC水平无明显变化(P0.05);OGTT和ITT曲线下面积均明显减少(P0.05);葡萄糖输注率较高脂组明显增加(P0.05);肝脏组织中p-IRS-2蛋白的表达减少,p-Akt、GLUT-2的表达增加(P0.05);肝脏组织中p-I?Bα、NF-?B蛋白的表达减少,下游炎性因子TNF-α、IL-6 m RNA水平降低(P0.05)。结论:Vaspin可促进肝脏组织IRS/PI3K/Akt信号通路的传导,改善大鼠的胰岛素敏感性,且Vaspin可抑制NF-?B信号分子的表达,减轻机体的炎症状态,进而改善大鼠的胰岛素抵抗状态,最终降低血糖。
[Abstract]:Objective: 1, to investigate whether Vaspin can improve insulin resistance in high fat fed rats, and 2, to explore whether Vaspin can improve insulin resistance of high fat fed rats by acting on IRS/PI3K/Akt and NF- 魏 B signaling pathway in liver. Methods: thirty 8-week-old male SD rats were randomly divided into normal group (NC group, n = 10) and model group (n = 20) after one week of adaptive feeding. The normal group was fed with normal diet, the model group was fed with high fat diet 16 Zhou Jianli insulin resistance model. Insulin resistance rats were randomly divided into hyperlipidemia group (HFD group, nong10 group) and 320ng/ml Vaspin intervention group (HFD Vaspin group). Vaspin protein solution was injected intraperitoneally into nun10). HFD Vaspin group once a day for 8 weeks. NC group and HFD group were given the corresponding volume of normal saline. Serum fasting blood glucose, (FBG), insulin, (FINS), triglyceride, (TG), total cholesterol, (TC), tumor necrosis factor- 伪 (TNF- 伪) were measured. Interleukin-6 (IL-6) levels were evaluated by oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) in rats. Insulin sensitivity of peripheral tissues was evaluated by hyperinsulin-glucose clamp test. The rat liver tissue was isolated and the expression of IRS/PI3K/Akt,NF- 魏 B signaling pathway and downstream inflammatory factor were detected by Western blot,RT-PCR. Results: after Vaspin intervention, serum FBG,FINS,TNF- 伪 and IL-6 concentrations decreased significantly (P0.05), while body weight and TG,TC level did not change significantly (P0.05). The area under); OGTT and ITT curve decreased significantly (P0.05). The glucose infusion rate was significantly higher than that in the high fat group (P0.05), while the expression of p-IRS-2 protein in liver tissue was decreased, and the expression of p-AkttGL-GLUT-2 was increased (P0.05). The expression of p-I?B 伪 and NF-?B protein decreased and the levels of TNF- 伪 and IL-6 m RNA decreased in liver tissues (P0.05). Conclusion: Vaspin can promote the transduction of IRS/PI3K/Akt signal pathway in liver tissue, improve insulin sensitivity in rats, and Vaspin can inhibit the expression of NF-?B signal molecule and alleviate the inflammatory state of the body. Then improve the insulin resistance of rats, and ultimately reduce blood sugar.
【学位授予单位】：山西医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R589
本文编号：2302002
[Abstract]:Objective: 1, to investigate whether Vaspin can improve insulin resistance in high fat fed rats, and 2, to explore whether Vaspin can improve insulin resistance of high fat fed rats by acting on IRS/PI3K/Akt and NF- 魏 B signaling pathway in liver. Methods: thirty 8-week-old male SD rats were randomly divided into normal group (NC group, n = 10) and model group (n = 20) after one week of adaptive feeding. The normal group was fed with normal diet, the model group was fed with high fat diet 16 Zhou Jianli insulin resistance model. Insulin resistance rats were randomly divided into hyperlipidemia group (HFD group, nong10 group) and 320ng/ml Vaspin intervention group (HFD Vaspin group). Vaspin protein solution was injected intraperitoneally into nun10). HFD Vaspin group once a day for 8 weeks. NC group and HFD group were given the corresponding volume of normal saline. Serum fasting blood glucose, (FBG), insulin, (FINS), triglyceride, (TG), total cholesterol, (TC), tumor necrosis factor- 伪 (TNF- 伪) were measured. Interleukin-6 (IL-6) levels were evaluated by oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) in rats. Insulin sensitivity of peripheral tissues was evaluated by hyperinsulin-glucose clamp test. The rat liver tissue was isolated and the expression of IRS/PI3K/Akt,NF- 魏 B signaling pathway and downstream inflammatory factor were detected by Western blot,RT-PCR. Results: after Vaspin intervention, serum FBG,FINS,TNF- 伪 and IL-6 concentrations decreased significantly (P0.05), while body weight and TG,TC level did not change significantly (P0.05). The area under); OGTT and ITT curve decreased significantly (P0.05). The glucose infusion rate was significantly higher than that in the high fat group (P0.05), while the expression of p-IRS-2 protein in liver tissue was decreased, and the expression of p-AkttGL-GLUT-2 was increased (P0.05). The expression of p-I?B 伪 and NF-?B protein decreased and the levels of TNF- 伪 and IL-6 m RNA decreased in liver tissues (P0.05). Conclusion: Vaspin can promote the transduction of IRS/PI3K/Akt signal pathway in liver tissue, improve insulin sensitivity in rats, and Vaspin can inhibit the expression of NF-?B signal molecule and alleviate the inflammatory state of the body. Then improve the insulin resistance of rats, and ultimately reduce blood sugar.
【学位授予单位】：山西医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R589
【参考文献】
相关期刊论文 前1条
1 ;Visceral adipose tissue-derived serine protease inhibitor: A unique insulin-sensitizing adipocytokine in obesity[J];中国分子心脏病学杂志;2005年05期
，本文编号：2302002
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