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高脂聯(lián)合地塞米松誘導(dǎo)小鼠急性脂肪肝模型的實(shí)驗(yàn)研究

發(fā)布時(shí)間:2018-04-23 02:40

  本文選題:地塞米松 + 高糖高脂飼料; 參考:《重慶醫(yī)學(xué)》2017年17期


【摘要】:目的研究地塞米松配高糖高脂飼料導(dǎo)致小鼠急性脂肪肝模型對(duì)藥物劑量與時(shí)間依存性特征,優(yōu)化藥物性脂肪肝模型的條件。方法雄性昆明鼠分為對(duì)照組及高糖高脂飼料加腹腔注射地塞米松組,分3個(gè)時(shí)間點(diǎn)處死小鼠,檢測(cè)小鼠體質(zhì)量,肝質(zhì)量,計(jì)算肝指數(shù),檢測(cè)血清及肝組織勻漿三酰甘油(TG),血清葡萄糖(GLU)含量,采用HE染色觀察肝組織病理變化。肝組織提取總RNA反轉(zhuǎn)錄表達(dá)相關(guān)基因,肝組織提取總蛋白通過Westen Blot檢測(cè)相關(guān)蛋白表達(dá)。結(jié)果與對(duì)照組比較,地塞米松模型組7d后,血及肝勻漿TG增高,肝指數(shù)增大,病理切片顯示,脂肪肝形成。反轉(zhuǎn)錄PCR顯示脂肪代謝相關(guān)基因表達(dá)有明顯改變。Western Blot顯示沉默信息調(diào)節(jié)因子1(SIRT1)明顯下降。但是,隨著地塞米松用量減少,時(shí)間延長(zhǎng),脂肪肝相關(guān)指標(biāo)降低,脂代謝基因PPAR、FOXO3、FXR逐漸回升,LXR逐漸下降,蛋白SIRT1逐漸回升。結(jié)論高糖高脂飼料加地塞米松大劑量腹腔注射可以建立小鼠急性脂肪肝模型,并且模型的維持對(duì)地塞米松的劑量和用藥時(shí)間有依存性,對(duì)于藥物干預(yù)實(shí)驗(yàn)具有指導(dǎo)意義。
[Abstract]:Objective to study the dose-dependent and time-dependent characteristics of acute fatty liver model induced by dexamethasone and high glucose and high fat diet, and to optimize the condition of drug induced fatty liver model. Methods male Kunming rats were divided into control group and high-glucose high-fat diet plus dexamethasone group. The mice were killed at three time points. The body weight, liver mass and liver index were measured. Serum and liver homogenate triglyceride (TGG) and serum glucose glu (GLU) contents were detected and the pathological changes of liver tissue were observed by HE staining. Total RNA was extracted from liver tissue to express related genes, and total protein was extracted from liver tissue to detect the expression of related protein by Westen Blot. Results compared with the control group, after 7 days of dexamethasone model group, TG and liver homogenate increased, liver index increased, pathological section showed fatty liver formation. Reverse transcription PCR showed significant changes in the expression of genes related to fat metabolism. Western Blot showed that silencing signaling factor 1 (sirt1) was significantly decreased. However, with the decrease of dexamethasone dosage and the prolongation of time, the relative indexes of fatty liver decreased, the lipid metabolism gene PPAR- FOXO _ 3 FXR gradually increased and the protein SIRT1 gradually decreased. Conclusion High glucose and high fat diet plus high dose dexamethasone intraperitoneal injection can establish acute fatty liver model in mice, and the maintenance of the model is dependent on the dose of dexamethasone and the time of drug use, which has guiding significance for drug intervention experiment.
【作者單位】: 三峽大學(xué)醫(yī)學(xué)院腫瘤微環(huán)境與免疫治療湖北省重點(diǎn)實(shí)驗(yàn)室;
【基金】:國(guó)家自然科學(xué)基金資助項(xiàng)目(81473461)
【分類號(hào)】:R-332;R575.5

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1 李玉紅,張震之,段衛(wèi)華,徐宗佩,張伯禮;小鼠急性脂肪肝模型的建立及脂肝清作用觀察[J];天津中醫(yī)學(xué)院學(xué)報(bào);2005年01期

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