本文選題：細(xì)胞色素P450_2E_1 + 脂肪性肝炎　； 參考：《川北醫(yī)學(xué)院》2017年碩士論文

【摘要】：目的:(1)建立細(xì)胞色素P450_2E_1(CYP2E1)基因敲除鼠的肥胖和酒精協(xié)同增效性脂肪性肝炎動物模型。(2)探討CYP2E1在酒精與高脂協(xié)同增效性脂肪性肝炎中的作用。方法:首先繁殖飼養(yǎng)CYP2E1基因敲除小鼠,并通過鼠尾基因鑒定篩選純合子。然后分別將7周齡雄性CYP2E1基因敲除鼠和野生型小鼠同時分為4個處理組:1)正常飼料(對照)組:胃造瘺術(shù)后,通過微量注射泵每日以2μl/min的流速,580kcal/kg/d的液體常規(guī)飼料,恒速恒量灌注小鼠;2)酒精組:胃造瘺術(shù)后,通過微量注射泵每日以2ul/min的流速,580kcal/kg/d的液體常規(guī)飼料及15g/kg/d的酒精,恒速恒量灌注小鼠;3)高脂高膽固醇組:胃造瘺術(shù)后,通過微量注射泵每日以2μl/min的流速,780kcal/kg/d的液體高脂飼料(含0.21%的膽固醇)恒速恒量灌注小鼠;4)酒精協(xié)同高脂高膽固醇組:胃造瘺術(shù)后,通過微量注射泵每日以2μl/min的流速,780kcal/kg/d的液體高脂飼料(含0.21%的膽固醇)及15g/kg/d的酒精,恒速恒量灌注小鼠。同時飼喂2周后,取肝臟冰凍切片樣本進行油紅O、常規(guī)HE染色分析。結(jié)果:提取肝臟組織進行病理學(xué)分析,發(fā)現(xiàn)肝臟細(xì)胞出現(xiàn)氣球樣變,偶見點狀壞死;油紅O染色可見大量脂肪滴。同時通過Real-Time q PCR檢測肝臟組織,發(fā)現(xiàn)酒精和高脂都能促進CYP2E1表達(dá)量增加,促進炎癥因子表達(dá),表明肥胖酒精協(xié)同增效性脂肪肝造模成功。結(jié)論:(1)成功構(gòu)建小鼠高脂與酒精協(xié)同作用下的肝炎模型。(2)發(fā)現(xiàn)CYP2E1在高脂、酒精、及高脂酒精共同作用下都有介導(dǎo)炎癥的作用。
[Abstract]:Objective: (1) to establish an animal model of obese and alcoholic synergistic fatty hepatitis in mice with cytochrome P4502E-1 (CYP2E1) knockout. (2) to investigate the role of CYP2E1 in synergistic fatty hepatitis between alcohol and hyperlipidemia. Methods: CYP2E1 knockout mice were bred and homozygotes were screened by mouse tail gene identification. Then male CYP2E1 knockout mice and wild-type mice were divided into four treatment groups: control group (control group) and male CYP2E1 knockout mouse group (control group). After gastrostomy, the rats were given a daily liquid diet of 580kcal / kg / d at a flow rate of 2 渭 l/min per day. After gastrostomy, the rats were perfused with constant speed and constant dose of alcohol at the flow rate of 580kcal / kg / d of liquid diet and alcohol of 15g/kg/d daily by microinjection pump. 3) the group of mice with high fat and high cholesterol was perfused with constant speed and constant quantity. After gastrostomy, the rats were treated by gastrostomy, and the rats were treated with high fat and high cholesterol after gastrostomy. After gastrostomy, mice were fed with liquid high-fat diet (containing 0.21% cholesterol) at a flow rate of 780kcal / kg / d at a flow rate of 2 渭 l/min per day by a microinjection pump. The mice were perfused with alcohol and hyperlipidemia and hypercholesterolemia group. Mice were infused with microinjection pump at a flow rate of 780kcal / kg / d of liquid high-fat diet (containing 0.21% cholesterol) and 15g/kg/d alcohol daily. After feeding for 2 weeks, the frozen liver sections were collected and analyzed by routine HE staining. Results: pathological analysis of liver tissues showed that there were balloon degeneration and occasional necrosis in liver cells, and a large number of fat droplets were found in oil red O staining. At the same time, the liver tissue was detected by Real-Time Q PCR. It was found that both alcohol and hyperlipidemia could increase the expression of CYP2E1 and promote the expression of inflammatory factors, which indicated that the model of fatty liver induced by obesity and alcohol synergism was successful. Conclusion: (1) the mouse model of hepatitis induced by hyperlipidemia and alcohol was successfully constructed. (2) it was found that CYP2E1 could mediate inflammation under the combined action of high fat, alcohol and high fat alcohol.
【學(xué)位授予單位】：川北醫(yī)學(xué)院
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R575.5

【參考文獻】

相關(guān)期刊論文 前10條

1 馬龍俊;;Kupffer細(xì)胞與肝纖維化關(guān)系的研究進展[J];宜春學(xué)院學(xué)報;2015年03期

2 倪國華;張t，

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