绿原酸对大鼠肝脏脂肪代谢调节机制研究

发布时间：2018-01-16 15:04

本文关键词：绿原酸对大鼠肝脏脂肪代谢调节机制研究　出处：《湖南农业大学》2014年硕士论文　论文类型：学位论文

【摘要】：目的：研究绿原酸对高脂诱导的肝脏脂肪代谢紊乱的分子作用机制。背景：生活方式和生活质量的改变,使得肥胖正在成为公共卫生一大难题,而肝脏作为机体第一大能量代谢器官,在脂肪摄入过量的情况下,易于发生脂肪代谢紊乱,严重将会病变为非酒精性脂肪肝炎。近年来,随着肥胖患病率发生居高不下,由此引发的一系列慢性疾病成为了诊疗难题。由于临床药物的副作用和疗效等问题,调整饮食结构,可以作为改善机体脂肪代谢,预防肝脏脂肪代谢紊乱的重要途径。天然产物绿原酸广泛存在于膳食中,在抗氧化,抗病毒,降血脂等多种功效方面表现优良。但是,绿原酸对肝脏脂肪代谢的调节机制有待深入研究。方法：体重130±10g的雄性SD大鼠,经过8天适应期喂养后,随机分成五组：空白对照组(NC组),每天灌胃超纯水；高脂肪模型组(HFD组),每天灌胃超纯水；低剂量绿原酸组(HFD-LC组),按照20mg·kg-1·d-1剂量灌胃绿原酸；高剂量绿原酸组(HFD-HC组),按照90mg·kg-1·d-1剂量灌胃绿原酸；阳性对照组(HFD-ROS组),按照罗格列酮3mg·kg-1·d-1剂量进行灌胃；其中空白对照组投放普通饲料,其余各组每天投放高脂肪饲料。12周后,大鼠麻醉处死后,眼球采血,检测血清TC, TG, LDL-c, HDL-c, FFA, ALT,瘦素。检测肝脏组织TG, Real time PCR检测LXRα、 SREBP-1c、ACCα、FAS、AP2、FAT/CD36、LPL、HMGCR、PPARa、CPT-1和CPT-2mRNA的表达。HE染色法方法观察肝脏组织病理变化。结果：绿原酸可以对高脂饲料诱导的体重增加起到抑制作用,并且改善血脂谱,改善高脂诱发的瘦素抵抗。绿原酸可以降低肝脏的重量、缓解肝脏脂肪的累积,基因表达结果揭示,第一,绿原酸降低了大鼠肝组织的LXRα、SREBP-1c表达,mRNA进而调控下游与脂肪合成有关表达；第二,绿原酸上调了大鼠肝ACCα、FAS mRNA组织表达,进而激活了和脂肪酸氧化相关的基因PPARa mRNA表达,CPT-1、CPT-2促进脂肪分解代谢；第三,绿原酸可以降低与脂肪酸摄入相关的基因的AP2、FAT/CD36表达。HE染色组织切片结果显示,高脂饲料引起肝脏组织出现大量空泡,mRAN脂滴积累明显,绿原酸可以有效明显减少脂肪引起的空泡,抑制肝脏组织中脂肪累积。结论：绿原酸可以通过调节肝脏核受体及其下游基因表达,有效改善高脂饲料喂饲诱发的大鼠肝脏脂肪代谢紊乱,抑制脂肪在肝脏组织的积累。
[Abstract]:Aim: to study the molecular mechanism of chlorogenic acid on fatty metabolic disorder induced by hyperlipidemia. Background: changes in lifestyle and quality of life have made obesity a public health challenge, while the liver, as the body's number one energy metabolism organ, is suffering from excessive fat intake. It is easy to develop the disorder of fat metabolism, which will change into non-alcoholic fatty liver disease. In recent years, the prevalence rate of obesity remains high. A series of chronic diseases caused by this has become a difficult problem in diagnosis and treatment. Because of the side effects and effects of clinical drugs, the adjustment of dietary structure can be used to improve the body fat metabolism. An important way to prevent hepatic fat metabolism disorder. Chlorogenic acid, a natural product, is widely found in diet, and has good performance in antioxidant, antiviral, and lipid-lowering functions. The regulation mechanism of Lv Yuan acid on hepatic fat metabolism needs further study. Methods: male SD rats weighing 130 卤10 g were randomly divided into five groups after feeding for 8 days. Hyperlipidemia model group, HFD group, daily intragastric infusion of ultra-pure water; The low dose Lv Yuan acid group (HFD-LC group) was administrated intragastrically according to 20mg 路kg-1 路d-1 dose. The high dose Lv Yuan acid group was treated by gastric instillation of Lv Yuan acid according to 90 mg 路kg-1 路d-1 dose of HFD-HC group. The positive control group (HFD-ROS group) was given rosiglitazone (3mg 路kg-1 路d-1) by gavage. The blank control group was fed with normal diet, the other groups were given high fat diet for 12 weeks. After the rats were killed under anesthesia, blood was collected from their eyeballs and serum TC-, TG-, LDL-c were detected. HDL-c, FFA, alt, leptin. Liver TGs, Real time PCR, LXR 伪 and SREBP-1ACC 伪 were detected. The expression of CPT-1 and CPT-2mRNA in AP2FAT-CD36 LPLX HMGCRT and PPARaN. The pathological changes of liver tissue were observed by HE staining. Results: Lv Yuan acid could inhibit the weight gain induced by high fat diet, improve the blood lipid profile and improve leptin resistance induced by high fat diet. Lv Yuan acid could reduce the weight of liver. The results of gene expression showed that: first, chlorogenic acid decreased the expression of LXR 伪 -SREBP-1c in rat liver and regulated the expression of LXR 伪 SREBP-1c downstream. Secondly, Lv Yuan up-regulated the expression of ACC 伪 -FAS mRNA in rat liver and activated the expression of PPARa mRNA, a gene related to fatty acid oxidation. CPT-2 promotes adipose catabolism; Third, chlorogenic acid can reduce the expression of AP2FAT-CD36 in fatty acid related genes. The results of HE staining showed that high fat diet caused a large number of vacuoles in liver tissue. The accumulation of mRAN lipid droplets was obvious, and Lv Yuan could effectively reduce the fat induced vacuoles and inhibit the fat accumulation in liver tissue. Conclusion: Lv Yuan acid can regulate the expression of liver nuclear receptor and its downstream genes. Effective improvement of High Fat Feed feeding The hepatic fat metabolism disorder induced by feeding inhibited the accumulation of fat in the liver tissue.
【学位授予单位】：湖南农业大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R285.5

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