乳脂肪前体物在LPS致肝细胞损伤时对脂代谢的影响

发布时间：2018-03-28 04:27

本文选题：脂多糖　切入点：肝细胞　出处：《河南农业大学》2015年硕士论文

【摘要】：亚急性瘤胃酸中毒(SARA)是一种常见的营养代谢病。当泌乳奶牛患SARA时,体内异常升高的脂多糖(LPS)会引起全身炎性反应,造成肝损伤,导致产乳性能下降,尤其是乳脂肪下降。乙酸和丁酸是合成乳脂的主要前体物质,能作为信号分子调控肝脏脂代谢。乳脂肪合成前体物在肝细胞损伤条件下对肝脏脂代谢的影响研究较少,本论文利用LPS致肝细胞损伤,再用乳脂肪前体物(乙酸和丁酸)处理细胞,利用荧光定量PCR方法检测细胞炎性信号、凋亡和脂代谢相关基因的表达水平,阐明乳脂肪前体物在LPS致肝细胞损伤时对肝细胞脂代谢的影响,为揭示SARA引起乳脂肪下降的原因提供前期理论基础。结果如下:LPS通过激活TLR4信号通路和凋亡信号促进肝细胞发生损伤和凋亡。LPS能促进肝细胞内脂肪酸的氧化及转运,抑制脂质的合成,通过促进PPARα、CPT、LPL、CD36、VLDLV基因转录水平、抑制PPARγ、SREBP-1c、ChREBP、FAS、ACC、SCD基因的转录表达。乙酸能通过激活肝细胞内AMPK信号通路,促进肝细胞内脂氧化作用,抑制脂合成。乙酸作用于肝细胞能促进PPARα、PPARγ、ChREBP及其下游基因的转录表达,抑制SREBP-1c、FAS、ACC的转录表达。乙酸能缓解LPS对脂肪合成和转运相关基因的抑制作用。β-羟基丁酸能通过激活肝细胞内AMPK信号通路,影响脂质的转运,促进脂质的氧化分解,抑制脂类的合成,减少肝脏中脂质的堆积;肝细胞发生损伤时,β-羟基丁酸对PPARα、PPARγ、ChREBP的促进作用减弱;并且BHBA在一定程度上能影响LPS调节脂肪酸转运的能力。
[Abstract]:Subacute rumen acidosis (SARAA) is a common nutritional metabolic disease. When lactating cows suffer from SARA, the abnormal elevation of lipopolysaccharide (LPS) in the body can cause systemic inflammatory reaction, lead to liver injury, and lead to a decline in milk-producing performance. Especially the decrease of milk fat. Acetic acid and butyric acid are the main precursors of the synthesis of milk fat, which can act as signal molecules to regulate the lipid metabolism of the liver. There is little research on the effect of the precursor of milk fat synthesis on the lipid metabolism of the liver under the condition of hepatocyte injury. In this study, hepatocytes were injured by LPS, then treated with milk fat precursors (acetic acid and butyric acid). The expression levels of inflammatory signals, apoptosis and lipid metabolism-related genes were detected by fluorescence quantitative PCR. To elucidate the effects of milk fat precursors on lipid metabolism of LPS induced hepatocyte injury. In order to reveal the cause of the decrease of milk fat induced by SARA, the results are as follows: SARA can promote the oxidation and transport of fatty acids in hepatocytes by activating TLR4 signaling pathway and apoptosis signal. Inhibition of lipid synthesis and inhibition of PPAR 纬 -SREBP-1c ChREBP- FAS-ACCSCD gene transcription by promoting the transcription level of PPAR 伪 -CPTP-LPL-CD36VLDLV gene. Acetic acid can promote lipid oxidation by activating the AMPK signaling pathway in hepatocytes. Inhibition of lipid synthesis. Acetic acid could promote the transcription and expression of PPAR 伪 -PPAR- 纬 -ChREBP and its downstream genes in hepatocytes. Inhibiting the transcription and expression of SREBP-1cFASACC. Acetic acid alleviates the inhibitory effect of LPS on adipose synthesis and transportation-related genes. 尾 -hydroxybutyric acid can affect lipid transport and promote lipid oxidative decomposition by activating AMPK signaling pathway in hepatocytes. 尾 -hydroxybutyric acid (尾 -hydroxybutyric acid) inhibited the synthesis of lipids and the accumulation of lipids in the liver, the promotion of 尾 -hydroxybutyric acid on PPAR 伪 -PPAR- 纬 -ChREBP was weakened, and BHBA could affect the ability of LPS to regulate the transport of fatty acids to some extent.
【学位授予单位】：河南农业大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：S852.3

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