| Recent years, due to rising living standards, lack of exercise time, the incidence ofnon-alcoholic fatty liver disease increases every year. Thus, the pathogenesis and influencingfactors of NAFLD are not yet completely understood. Lipid metabolism play an important role inthe occurrence and development of NAFLD. Recent studies found that lipid accumulation in theliver cause that the use and clear of lipid in the body is imbalance, eventually leading to liverdamage. Nuclear factor erythroid2-related factor2(Nrf2) is closely related to the body’s defensesystem, and it plays an important role in maintaining the stable function of liver. Thus, theinvestigation of the expression of Nrf2and lipid metabolism-related genes in NALFD, and theregulatory role of Nrf2on lipid metabolism-related genes can contribute to our in depth to explorethe relationship between lipid metabolism disorders and NAFLD, and can conduce to acomprehensive knowledge of the pathogenesis of NAFLD in molecule.In this study, the wild-type and Nrf2-null ICR mice are experimental animals. Our previousestablished high-fat feeding method is used to copy non-alcoholic fatty liver model. Theexperimental animals were randomly divided into eight groups: wild-type four-week control group(A), four weeks model group (B), eight weeks the control group (C), eight weeks model group(D),and Nrf2-null mice four-week control group(E), four weeks model group(F), eight weeks thecontrol group(G), eight weeks model group(H).Group A and E were fed with normal diet for4weeks; Group C and G were fed with normal diet for8weeks; Group B and F were fed with highfat diet for4weeks; Group D and H were fed with high fat diet for8weeks. Evaluation thechanges of lipid metabolism from biochemical parameters and histopathological changes.RT-PCRanalysis of liver lipid metabolism related gene mRNA expression. From the changes of lipidmetabolism-related gene expression in the NAFLD disease process and Nrf2regulation of lipidmetabolism related genes involved in NAFLD occurrence to discuss the role of Nrf2and lipidmetabolism related gene induce to the disorder of lipid metabolism in the NAFLD formationprocess. The main contents and results are as follows:1. The changes of lipid metabolism in the NAFLD miceEstablish a high-fat dietinduced mouse model of NAFLDby the laboratory, in accordancewith the test plan were fed four weeks and eight weeks. Product the mouse liver biopsy to observethe pathological changes and detecte serum TC, TG, HDL and LDL levels.Pathology results showed that the model mice of wild style in four weeks, liver cell swelling, a small amount offatdroplets,after eight weeks model group were significantly larger volume of liver cells, obvioussteatosis, including pulp is filled with a lot of fat vacuoles. In addition to the model mice liver cellscompared with wild-type mice in model group, Nrf2-null mice vacuolar degeneration occurs,significantly increased the number of lipid droplets in pack slurry, fatty degeneration of the liver ismore obvious, more serious lesions. Serological results showed that after4weeks of high fat dietfed, compared with the control group, the content of serum TC, HDL, LDL was increased after8weeks of feeding elevated above indicators are highly significant (P <0.01). TG content in serumwas significantly lower (P <0.01). The results prove that high-fat diet-induced lipid metabolismdisorders.2. The changes of lipid metabolism-related gene expression in the NAFLD mice modelDetect the mRNA expression changes of lipid metabolism-related genes in mice liver byRT-PCT.The results showed that by the high fat diet-induced4weeks,compared with the controlgroup,the amount of PPARα, PPARγ, PGC-1α expression in the liver of the wild-type model grouprespectively decreased by19%,12%and15%.The amount of UCP-2, SREBP-1c, FAS, ACC-1expression levelswere respectively increased by221%,209%,92%and103%.By the high fatdiet-induced8weeks,the amount of PPARα, PPARγ, PGC-1α expression in the liver of thewild-type model group respectively decreased by28%,25%and28%.The expression leveldecreased significantly(P<0.01).The amount of UCP-2, SREBP-1c, FAS, ACC-1expressionlevelswere respectively increased by388%,334%,134%and197%,expression levels tended toincrease significantly(P<0.01).These results suggest that high fat diet-induced extension of time,compared with the blank control group, the expression of PPARα, PPARγ, PGC-1α mRNA inwild-type mice is decreased,UCP-2, SREBP-1c, FASandACC-1mRNA expression levels isincreased. PGC-1αcan be an activatoras auxiliary of the PPARs.PPARs is a transcriptionalregulatory factor that is closely related to lipid balance when its expression is suppressed, will leadto a series of proteins and enzymes associated with lipid metabolism gene transcription reducetoresult to lipid metabolism disorders. UCP-2mRNA overexpression will consume large amountsof ATP, reduced ability of the body’s resistance to the "two-hit". SREBP-1c expression increasewill promoteadipogenesis gene expression, so that the increase in fatty acid synthesis andaccelerated triglyceride accumulation. FAS can catalytic fat regeneration of the liver to producelarge amounts of free fatty acids. FAS activity and increase in the number will cause thegeneration and deposition of lipid in animal body. ACC-1expression levels increase will increasethe de novo synthesis and uptake of fatty acids in the liver.Experimental results show that NAFLDmodel lipid metabolism disorders, liver function abnormalities, the abnormal gene expressionpromotes the occurrence of NAFLD.3. Nrf2regulation of lipid metabolism related gene mRNA expressionCompared with the wild-type mice in model group,extension of time with the high fat diet-induced, Nrf2-null mice lipid metabolism related gene mRNA is much more dramatic change.In addition, the Nrf2gene expression in wild-type mice liver gradually increased. DescriptionNrf2regulation of lipid metabolism related genes in the NAFLD process has a protective effect onthe liver.Above findings in process of NAFLD formation, lipid metabolism gene expression isabnormal.Nrf2mRNA expression closely contact with the NAFLD disease developmentprocess.Nrf2through the regulation of lipid metabolism related genes play a protective effect onthe liver.This target has important significance for the in-depth understanding of the pathogenesisof NAFLD, explore new drug for the treatment of NAFLD. |
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