【摘要】：目的:1、探討Vaspin能否改善高脂喂養(yǎng)大鼠的胰島素抵抗;2、探討Vaspin是否通過作用于肝臟的IRS/PI3K/Akt及NF-κB信號通路,進(jìn)而改善高脂喂養(yǎng)大鼠的胰島素抵抗。方法:30只8周齡雄性SD大鼠,適應(yīng)性喂養(yǎng)一周后,隨機(jī)分為正常組(NC組,n=10)和模型組(n=20)。正常組喂以正常飼料,模型組以高脂飼料喂養(yǎng)16周建立胰島素抵抗模型。胰島素抵抗大鼠隨機(jī)分為高脂組(HFD組,n=10)和320ng/ml Vaspin干預(yù)組(HFD+Vaspin組,n=10)。HFD+Vaspin組經(jīng)腹腔注射Vaspin蛋白溶液,每日1次,共干預(yù)8周,NC組和HFD組分別給予相應(yīng)體積的生理鹽水。干預(yù)結(jié)束后稱重并留取血標(biāo)本,檢測血清中空腹血糖(FBG)、空腹胰島素(FINS)、甘油三酯(TG)、總膽固醇(TC)、腫瘤壞死因子-α(TNF-α)、白介素-6(IL-6)的水平,行口服葡萄糖耐量試驗(yàn)(OGTT)和胰島素耐受性試驗(yàn)(ITT)評估大鼠糖耐量及胰島素耐受性,行高胰島素-正葡萄糖鉗夾試驗(yàn)評估外周組織胰島素敏感性的變化。分離大鼠肝臟組織,采用Western blot、RT-PCR檢測大鼠肝臟IRS/PI3K/Akt、NF-κB信號通路及下游炎性因子的表達(dá)水平。結(jié)果:Vaspin干預(yù)后,血清FBG、FINS、TNF-α、IL-6濃度顯著降低(P0.05),而體重、TG、TC水平無明顯變化(P0.05);OGTT和ITT曲線下面積均明顯減少(P0.05);葡萄糖輸注率較高脂組明顯增加(P0.05);肝臟組織中p-IRS-2蛋白的表達(dá)減少,p-Akt、GLUT-2的表達(dá)增加(P0.05);肝臟組織中p-I?Bα、NF-?B蛋白的表達(dá)減少,下游炎性因子TNF-α、IL-6 m RNA水平降低(P0.05)。結(jié)論:Vaspin可促進(jìn)肝臟組織IRS/PI3K/Akt信號通路的傳導(dǎo),改善大鼠的胰島素敏感性,且Vaspin可抑制NF-?B信號分子的表達(dá),減輕機(jī)體的炎癥狀態(tài),進(jìn)而改善大鼠的胰島素抵抗?fàn)顟B(tài),最終降低血糖。
[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- 偽 (TNF- 偽) 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- 偽 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 偽 and NF-?B protein decreased and the levels of TNF- 偽 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.
【學(xué)位授予單位】：山西醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R589

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相關(guān)期刊論文 前1條

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本文編號：2302002