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Regulatory Effects of Tea Polyphenols on Peroxisome Proliferator-Activated Receptor α and Nuclear Factor-κB in Alcoholic Liver Disease Models

Author: TangYuanZuo
Tutor: GuanXiaoQin
School: Chongqing Medical University
Course: Pathology
Keywords: Tea polyphenols Alcoholic liver disease Peroxisome proliferator-activated receptor α NF-κB
CLC: R285.5
Type: Master's thesis
Year: 2009
Downloads: 89
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Abstract


Objective observation tea polyphenols animal and cell models of alcoholic liver disease (ALD) peroxisome proliferator-activated receptor α (PPARα) and nuclear factor-kappa B (NF-κB) expression and activity of the regulatory role to explore The protective effect of tea polyphenols on alcoholic liver disease and possible mechanisms. Method 1. Vivo experiment 30 Wistar rats were randomly divided into three groups: control group with normal diet; model group in the control group on the basis of the use of alcohol; TPs group on the basis of the model group given tea polyphenols, 7 The rats were sacrificed on weekends. Detection of serum ALT, AST, MDA levels. Conventional HE staining observed by light microscopy the basic liver tissue pathological changes; Sudan Ⅳ staining fatty degeneration of the liver tissue. RT-PCR measured liver tissue PPARαmRNA expression; gel shift electrophoresis (EMSA) measuring liver tissue NF-κB activity changes. Vitro cultured human immortalized normal fetal liver L02 cell line one day, adherent divided into five groups: control group conventional cultured for 6 days; model group with alcohol-induced 3 days after conventional cultured for 3 days; using tea polyphenols period intervention model group is divided into: the Tea Group A three days after pre-treatment with tea polyphenols modeling three days and then alcohol; the Tea Group B at the same time with alcohol and tea polyphenols intervention after 3 days of conventional cultured for 3 days; the Tea Group C with alcohol 3 days after the re-use of tea polyphenols modeling for 3 days. 7 days cycle passaged for 4 weeks. Oil Red O staining observed by light microscopy groups L02 cell lipid droplets change; groups L02 cells ROS fluorescent coloring fluorescence microscopy. Detect the L02 cell culture medium ALT, AST, GGT, TG content; intracellular ROS content. RT-PCR measured cell the PPARα, NF-κB and IκB mRNA expression; EMSA L02 cells measured NF-κB activity changes. Results 1. Successfully establish model of ALD animal. Model group rats serum liver enzymes indicators in ALT, AST and lipid peroxidation degradation products MDA was significantly higher in rats the tea polyphenols serum ALT, AST, MDA content was significantly lower than that in the model group. 3 model rats fatty degeneration obvious area of ??steatosis greater than 30%, no significant inflammatory cell infiltration and fibrosis; compared with the model group, the TP group all rats steatosis area is reduced, the degree mitigate . 4 compared with the control rats the model group PPARαmRNA reduced expression of NF-κB activity increased; compared with the model group, the tea polyphenols rats PPARαmRNA expression elevated, NF-κB activity weakened. Successfully established alcoholic fatty change L02 cell model, the MTT results showed that tea polyphenols can improve in a certain concentration range vitro L02 cells ALD damage. 6 compared with the model group Tea A, B, C group steatosis area is small, the degree of light; reactive oxygen fluorescent coloring dark; decrease in ALT, AST, GGT, TG, ROS levels. 7 compared with the control group, L02 cells PPARαmRNA of model group decreased expression, IκB mRNA decreased expression, NF-κB mRNA expression increased NF-κB activity increased; compared with the model group, Tea A, B, C group L02 cell PPARαmRNA expression elevated, IκB mRNA expression increased, NF-κB mRNA expression decreased NF-κB activity weakened. Conclusion 1. Oxidative stress and lipid peroxidation involved in the occurrence of ALD, tea polyphenols may improve antioxidant role of ALD model of in vivo and in vitro experiments liver damage. The molecular mechanism of the protective effect of tea polyphenols on ALD involved raised PPARα expression and inhibition of NF-κB activation. 3 polyphenols of ALD occurrence development intervention, and in advance, at the same time or delay the use of tea polyphenols to intervene in vitro ALD model can alleviate the ALD lesions of the liver cells have certain protective efficacy.

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