| Objective: Nonalcoholic fatty liver disease (NAFLD) is clinicopathologicsyndrome in which a lot of triglyceride are gathered in the liver cells.NAFLDIncludes nonalcoholic simple fatty liver(NAFL),non-alcoholic steatohepatitis(NASH),NASH-related liver fibrosis、 cirrhosis and heptic cancer.With theimprovement of living habits and changes in dietary habits,more and morepeople are suffering from nonalcoholic fatty liver disease which eventually aredeveloped into liver cirrhosis.Non-alcoholic fatty liver disease has become oneof most common liver diseases,seriously harm people’s life and health.Therefore to clarify the pathogenesis of nonalcoholic fatty liver disease,is ofan extremely important theory value and the clinical value of clinical pathselection to prevention,diagnosis and treatment of NAFLD.But detailedpathogenesis of NAFLD is still not clear and may be associated withgenetic,environmental,metabolic factors,caused by factors such as stress,oftenassociated with obesity,Hyperlipidemia,diabetes mellitus and insulin resistancesyndrome (IRS) or metabolic syndrome (MS).In recent years,a growing body ofresearchs suggest that abnormal lipid metabolism and insulin resistance (IR) isthe central component of the pathogenesis of NAFLD.ChREBP and its targetgenes PNPLA3is a key factor in the development of the occurrence of insulinresistance,In recent years,more studies have found that ChREBP and its target genes PNPLA3can increase the susceptibility of NAFLD,Closely linked withinsulin resistance,hepatitis,liver fibrosis,are involved in the pathogenesis ofNAFLD,For the study of the relationship between ChREBP and PNPLA3andwhether they are involved in the pathogenesis of NAFLD by insulinresistance,the current related research report is less.The study were aimed tomake NAFLD rat model with high fat diet,investigate the expressions ofChREBP and its target gene PNPLA3in rat liver tissues and explore their rolesin the pathogenesis of NAFLD,This has important theoretical value for theimprovement of the pathogenesis of nonalcoholic fatty liver disease,for thetreatment of non-alcoholic fatty liver disease also has important clinicalvalue.Methods:in this experiment male,48SD rat weighted180g-220g wereadaptabilly fed for a week and were randomedly divided into2group:controlgroup24only (normal fed diet) and non-alcohol fat liver diseases model group24only (a high-fat diet),free access to water and eating,at room temperature (20±2)℃,appropriate natural light and shade alternate for12h,big rat weight,andlength,and rat appetite,and skin,and hair situation were observed.Afterrandomization,at the end of4th、8th and12th week8rats in each group wererespectively killed Blood of rat from the inferior vena cava were collected andaspartate aminotransferase (AST),alanine amino transferase (ALT),totalcholesterol (TC),triglyceride (TG) levels,fasting blood glucose (FBG) andfasting serum insulin(FINS) level were detected and the insulin sensitivityindex ISI=ln[1/(FINSxFBG)] was calculates.Pathogenetical changes of the liver were observed with HE staining in optical microscope.The activity of fattydegeneration of the liver, inflammation and fibrosis in rat liver tissues wereevaluated.the level of preotein expression of ChREBP and ACC was detectedwith immunhistological chemistry.ChREBP PNPLA3mRNA expression wasdetected with RT-PCR in the liver.Results:1、 rat NAFLD model wassuccessfully constructed with a high-fat diet.in the control group rats liverlobule structure was complete,clear,and liver distribution cables were radiatedaround a central vein,and the biochemical markers were in the normal range;inthe liver tissue few protein expression of ChREBP and ACC were visible;2、compared with control group, in model group rat weight were increased,espically the volume of liver was obviously increased,fat drops deposition wasvisible in liver cell.with time extending degrees of the liver fat chang wereaggravated,and different degree of inflammatory cell infiltration and necrosiswere discovred,the levels of AST, ALT, TC and TG level were obviouslyelevated in model group compared with control group (P<0.05),and bloodFBG,and FINS level were much more elevated than in control group(P<0.05).with feeding time increased,blood FBG,and FINS level were graduallyelevated and IsI was markably declined (P<0.05);3、In rat liver tissue of modelgroups,ChREBP,ACC protein and ChREBP,PNPLA3mRNA expression wereincreased compared with control group (P<0.05).with time extending,itsexpression were significantly increased (P<0.05).4、Correlation analysis showedthat in the model group,ChREBP mRNA expression was positively correlated with the ACC and PNPLA3,serum levels of AST,ALT,scores of hepaticflammatory activity (and acc:r=0.409,P<0.05,and PNPLA3:r=0.498,P<0.05,andALT、 AST:r=0.677,P<0.01,r=0.729,P<0.01, with And liver inflammationacore:r=0.566,P<0.01),and had negative correlation IsI (r=-0.611,P<0.01);PNPLA3mRNA expression were positively correlated with serum levels ofAST, ALT, liver inflammation activity scores (and AST、 ALT:r=0.663,P<0.01,r=0.736,P<0.01,And liver inflammation acore:r=0.478, P<0.05), andnegatively correlated with IsI (r=-0.694,P<0.01).conclusion：1、High fat dietscan be successfully made. rats NAFLD are characterized with elevatedtransaminase, obesity, hyperlipidemia, and insulin resistance. Lipid metabolicdisturbance and insulin resistance are associated with NAFLD.2、in controlgroup the expressions of ChREBP, ACC in rat liver are low,whereas the mRNAand protein expressions of ChREBP, ACC,PNPLA3are increased.With timeof the model extending, their expressions are markedly increased.Increasedexpression of hepatic ChREBP could activate a series of expression of genesinvolved in lipid synthesis such as ACC and PNPLA3,which promote theformation of fatty liver.3、the expression of ChREBP and its target genePNPLA3are correlated with extent of hepatic inflammation, liver function andinsulin sensitivity index and so on, which possibly participates in the mediationof insulin resistance and plays an important role in the pathogenesis of. |
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