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Fibrate lipid-lowering drugs are a class of synthetic peroxisome proliferator-activated receptor α (PPARα) ligand, can be effective in delaying the process of the development of atherosclerosis, is currently the most effective drugs for lowering TG , at the same time, increased HDL-C also has a strong role. Fenofibrate (fenofibrate) is the the clinical most common applications of lipid-lowering drugs. However, the current application of the fibrate is not different from the PPAR-specific ligand, therefore, the development of more effective PPAR subtype-specific ligand or agonist of the \The side effects will be smaller and broader clinical indications. In this context, we have to transform the of fenofibrate chemical structure, synthesis of a new fibrate compounds FC (the New a fibrate chemicalcompound FC). In this study, using an animal model of hyperlipidemia observed lipid-lowering effects of the new the fibrates compounds FC and explore its possible mechanism of action from the two aspects of the anti-oxidative stress, activation of PPAR pathway. The results are as follows: 1.FC on egg yolk induced mouse acute hyperlipidemia 1.1 FC yolk milk due to high cholesterol serum TG, TG, and HDL-C, LDL-C content injection of egg yolk model mice after serum TG, TC, LDL levels were significantly higher than in normal mice; the preventive give FC30d, FC 80mg/kg significantly lower TG, TC, LDL content. And LDL / HDL model group than normal mice significantly increased; FC 80mg/kg, 40mg/kg group compared with the model group can significantly reduce the LDL / HDL. 1.2 FC acute hypercholesterolemia mice Liver histology impact after the injection of egg yolk model mice liver tissue slightly vacuolar fatty degeneration of the liver cells, and have more swelling of the liver cells, and FC80mg/kg group fatty degeneration of the liver cells disappeared, Light microscopy showed a little swelling of the liver cells. Impact of hyperlipidemia 2.FC rats on the high fat diet induced 2.1 FC for high cholesterol serum TG, TC, HDL-C, LDL-C, FFA and atherogenic index AI, feeding fat feed the model serum TG, TC, LDL-c and FFA levels were significantly increased, FC160, of 80, 40 mg / kg and fenofibrate could reduce its serum TG, TC, LDL-c and FFA levels , FC 160,80 mg / kg role significantly. Model serum HDL-c level significantly reduce FC 160, 80 mg / kg and non fenofibrate increased HDL-c values ??can. The model rats arteriosclerosis index (AI) was significantly higher, FC 160, 80 mg / kg and fenofibrate significantly reduced its AI. Hemodynamic changes in rat whole blood flow change 2.2 FC high cholesterol high cholesterol can lead to increased blood viscosity, and ultimately induces the formation of blood clots and AS. Lower blood lipids, improve the cut rate of red blood cells, preventing red blood cell aggregation, reduce blood viscosity on the prevention of the formation of the AS and thrombosis major significance. Whole blood blood viscosity model rats fed a high fat diet, the low shear rate increases FC of 160 mg / kg group can significantly reduce blood viscosity of whole blood, FC 80mg/kg group can reduce high blood fat rat whole blood, high shear rate. 2.3 FC of high cholesterol in rat liver histopathological light microscopy showed normal morphology of normal liver tissue, fat model group rats steatosis, edema, with little necrosis phenomenon, a large number of lipid droplets accumulation of intracellular and gap liver structure of the entire FC 160 mg / kg group, fatty degeneration of the liver cell number compared with the model group significantly reduce edema, necrosis significantly reduced, similar positive drug fenofibrate group and FC160 mg / kg group, that new fibrate compounds FC to reduce hyperlipidemia rat liver lipid deposition, prevent the occurrence of fatty liver. 2.4 FC high blood lipids in rat liver tissue MDA content and SOD, GSH-Px activity affect hyperlipidemia lipid peroxidation can lead to damage of the endothelial cells, and lipid peroxidation resulting in increased production of MDA SOD, GSH-Px activity was reduced, but to accelerate the formation of AS. Therefore, the adjustment of lipoprotein metabolism, prevent lipoprotein lipid peroxidation, more meaningful against the formation of AS, this study found that the model group and the normal control group, liver MDA content significantly increased SOD GSH-Px activity was significantly reduced, suggesting that rats with experimental hyperlipidemia associated with a reduction of free radicals metabolism disorders and antioxidant enzyme activities. Compared with the model group, FC160, 80 mg / kg group could significantly reduce hyperlipidemia rat liver MDA content increased its of SOD, GSH-Px activity. 2.5 FC RT-PCR results show the impact of high blood cholesterol in rat adipose tissue of PPAR-αmRNA and of PPAR-γmRNA expression rat adipose tissue in the model group PPAR-α/γmRNA expression was significantly reduced compared with the normal group, the difference is significant. FC 160,80,40 mg / kg group and model group PPAR-α/γmRNA expression was significantly higher, especially TFB160, 80mg/kg group the most significant. 2.6 FC of high blood cholesterol in rat adipose tissue PPAR-α / γ protein the impact Westernblot results show rat adipose tissue in the model group of high cholesterol PPAR-α / γ protein expression in the normal group significantly reduced, FC 160,80 mg / kg can significantly promote its PPAR-α / γ protein. Conclusion: The new fibrate compounds FC elevated hyperlipidemic mice, rat serum HDL-c, reduce its serum TC, TG, LDL-c and MDA levels, increased activity of SOD, GSH-Px, and lower TC / HDL-c, and LDL-c/HDL-c ratio, reducing the viscosity of the whole blood; promote adipose tissue of PPAR-α / γ gene and protein expression, indicating that FC might by regulating the plasma lipoprotein - cholesterol metabolism, improve blood viscosity, enhanced activity of antioxidant enzymes, reducing oxygen free radical damage, promote PPAR-α / γ expression pathways play a role in prevention and treatment of AS.
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