本文關(guān)鍵詞：利拉魯肽對(duì)非酒精性脂肪肝大鼠模型療效評(píng)價(jià)和作用機(jī)制研究　出處：《安徽醫(yī)科大學(xué)》2017年碩士論文　論文類型：學(xué)位論文

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【摘要】：目的(1)采用氫質(zhì)子磁共振波譜(~1H-MRS)、病理及血清指標(biāo)來(lái)評(píng)價(jià)利拉魯肽治療非酒精性脂肪肝大鼠模型的療效;(2)探討分析利拉魯肽對(duì)非酒精性脂肪肝病模型大鼠血清及肝組織FGF21水平的影響以及可能機(jī)制。方法(1)清潔級(jí)雄性SD大鼠32只,隨機(jī)分為高脂組20只和正常對(duì)照組12只,高脂組造模成功后隨機(jī)分為利拉魯肽組和安慰劑組,繼續(xù)予高脂飲食并分別予皮下注射利拉魯肽或生理鹽水,對(duì)照組予普通飼料喂養(yǎng)。(2)干預(yù)16周末,~1H-MRS檢測(cè)各組大鼠肝臟相對(duì)脂肪含量,并行肝組織病理HE染色及生化、肝組織勻漿等指標(biāo)檢測(cè);(3)酶聯(lián)免疫吸附測(cè)定法(Elisa)測(cè)定三組大鼠血清FGF21濃度,蛋白免疫印跡法(Western blot)測(cè)定肝組織細(xì)胞裂解液中FGF21含量;(4)蛋白免疫印跡法對(duì)肝細(xì)胞內(nèi)PPAR a及PPAR r蛋白表達(dá)情況進(jìn)行相對(duì)定量研究;(5)Image J軟件分析蛋白條帶的灰度值,IPP圖像軟件分析免疫組化蛋白相對(duì)含量;采用SPSS 17.0統(tǒng)計(jì)軟件行正態(tài)分布性檢驗(yàn),采用Sigma plot12.5作圖,用“?x±s”來(lái)表示符合正態(tài)分布的所有計(jì)量資料;采用單因素方差分析來(lái)分析組間差異,其中采用SNK法進(jìn)行兩兩比較;采用多組獨(dú)立樣本秩和檢驗(yàn)對(duì)有序定性資料進(jìn)行檢驗(yàn)。結(jié)果(1)與安慰劑組相比,利拉魯肽組大鼠體質(zhì)量、肝指數(shù)、胰島素抵抗指數(shù)(HOMA-IR)、血清甘油三酯(TG)、膽固醇(CHO)、低密度脂蛋白(LDL)、空腹胰島素(FINS)、谷丙轉(zhuǎn)氨酶(ALT)、肝勻漿TG及CHO均明顯下降,差異有統(tǒng)計(jì)學(xué)意義(P0.05);三組空腹血糖(FBG)、高密度脂蛋白(HDL)無(wú)明顯差異;(2)與安慰劑組相比,利拉魯肽組大鼠肝組織病理及~1H-MRS結(jié)果示肝臟脂肪變性程度明顯減輕甚至恢復(fù)正常,肝內(nèi)相對(duì)脂肪含量明顯減少(26.8±1.30 vs 13.0±0.71,P0.05);(3)血清中,安慰劑組FGF21濃度較利拉魯肽組和正常對(duì)照組明顯升高,(637.53±14.12 vs 509.49±18.84,P0.05),利拉魯肽組與正常對(duì)照組差異無(wú)統(tǒng)計(jì)學(xué)意義(509.49±18.84 vs 503.98±20.23,P0.05);肝組織細(xì)胞裂解液中,安慰劑組FGF21含量明顯低于利拉魯肽組及正常對(duì)照組(1.38±0.23vs 2.50±0.78 vs 2.46±0.49,P0.05),利拉魯肽組與正常對(duì)照組FGF21差異無(wú)統(tǒng)計(jì)學(xué)意義(2.50±0.78 vs 2.46±0.49,P0.05);(4)與安慰劑組相比,利拉魯肽組大鼠肝組織PPARα表達(dá)明顯增加(0.50±0.07 vs 0.67±0.06,P0.05),利拉魯肽組和正常對(duì)照組差異無(wú)統(tǒng)計(jì)學(xué)意義(0.67±0.06 vs 0.71±0.07,P0.05);(5)與正常對(duì)照組相比,利拉魯肽組和安慰劑組大鼠肝組織PPARγ表達(dá)明顯減少(0.73±0.06 vs 0.65±0.56 vs 0.62±0.06,P0.05),利拉魯肽組較安慰劑組表達(dá)較高,但差異無(wú)統(tǒng)計(jì)學(xué)意義(0.65±0.56 vs 0.62±0.06,P0.05)結(jié)論(1)利拉魯肽能明顯減輕高脂飲食誘導(dǎo)的NAFLD大鼠體質(zhì)量,改善肝指數(shù)和肝臟相對(duì)脂肪含量;(2)利拉魯肽改善NAFLD,促進(jìn)FGF21的表達(dá),其機(jī)制可能與利拉魯肽上調(diào)肝組織PPARα表達(dá)有關(guān);
[Abstract]:Objective (1) using proton magnetic resonance spectroscopy (~1H-MRS), and to evaluate the effect of serum index of pathological model of liraglutide in the treatment of nonalcoholic fatty liver rats; (2) investigate effects of liraglutide on serum FGF21 level and liver tissues of rats with non alcoholic fatty liver disease model and possible mechanisms. (1) male SD 32 rats were randomly divided into high-fat group 20 rats and 12 rats in normal control group, hyperlipidemia group rats were randomly divided into liraglutide group and the placebo group to a high-fat diet and then were treated with subcutaneous injection of liraglutide or saline, the control group was given common feed. (2) 16 weeks intervention ~1H-MRS detection of liver of rats relative fat content, hepatic tissue biochemical and pathological HE staining, detection of liver homogenate and other indicators; (3) enzyme-linked immunosorbent assay (Elisa) determination of serum FGF21 concentration of three protein group, India Trace method (Western blot) for determination of the content of FGF21 in liver tissue in cell lysate; (4) Western blot of liver cells in PPAR A and PPAR R protein expressions were used for relative quantitative study; (5) Image J software to analyze the gray level of protein bands, analysis of the relative content of protein by immunohistochemistry IPP image software; using SPSS 17 statistical software for test of normal distribution, using Sigma plot12.5 mapping, with "x + S?" said to comply with all normal distribution measurement data; using the single factor analysis of variance to analyze the differences between groups, of which 22 were compared by SNK method; using multiple sets of independent samples rank sum test. In order to test the qualitative data. Results (1) compared with the placebo group, body weight, liraglutide group rats liver index, insulin resistance index (HOMA-IR), serum triglyceride (TG), cholesterol (CHO), low density lipoprotein (LDL), fasting insulin (FINS), valley Alanine aminotransferase (ALT), liver homogenate TG and CHO were significantly decreased, the difference was statistically significant (P0.05); the three groups of fasting blood glucose (FBG), high density lipoprotein (HDL) had no significant difference; (2) compared with the placebo group, the liver tissue pathological group Liraru peptide and ~1H-MRS showed fatty liver degeneration was significantly reduced and even returned to normal, liver fat relative content decreased significantly (26.8 + 1.30 vs 13 + 0.71, P0.05); (3) serum FGF21 concentration was significantly higher than the placebo group, Liraru peptide group and normal control group, (637.53 + 14.12 vs 509.49 + 18.84, P0.05), peptide group and Liraru the control group had no significant difference (509.49 + 18.84 vs 503.98 + 20.23, P0.05); liver tissue in the cell lysate, the placebo group was obviously lower than that of Liraru FGF21 peptide group and normal control group (1.38 + 0.23vs 2.50 + 0.78 vs 2.46 + 0.49, P0.05), Liraru peptide group and normal control group FGF2 There was no significant difference between 1 (2.50 + 0.78 vs 2.46 + 0.49, P0.05); (4) compared with the placebo group, the expression of Liraru in liver tissue of rats PPAR alpha peptide significantly increased (0.50 + 0.07 vs 0.67 + 0.06, P0.05), Liraru peptide group and the control group had no significant difference (0.67 + 0.06 vs 0.71 + 0.07, P0.05); (5) compared with the normal control group, the expression of Liraru peptide group and the placebo group of rat liver tissue PPAR was decreased (0.73 + 0.06 vs 0.65 + 0.56 vs 0.62 + 0.06, P0.05), Liraru peptide group than in the placebo group was higher, but the difference was not statistically significant (0.65 0.62 + 0.06 + 0.56 vs, P0.05) conclusion (1) Liraru peptide can significantly reduce the body mass of NAFLD rats induced by high fat diet, improve the liver index and relative liver fat content; (2) Liraru peptides improve NAFLD, promote the expression of FGF21, and its mechanism may be related to liver tissues Liraru peptide PPAR expression;

【學(xué)位授予單位】：安徽醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R575;R-332

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