Expression Of SIRT1 In Liver Tissue Of NAFLD Rat Induced By High Uric Acid And The Effect Of Resveratrol On It

Objective According to the effect of resveratrol on high uric acid mediated NAFLD rat serology,histopathology and PCR in SIRT1,FOXO3a and NF-κB expression indexes determined curative effect of resveratrol on high uric acid mediated NAFLD and liver cancer precancerous lesions associated with NAFLD.Explore the resveratrol mechanism of the prevention and treatment of high uric acid mediated NAFLD.This study aims to clarify the role and molecular mechanism of SIRT1 expression and regulation of NAFLD induced by uric acid in liver inflammatory injury in rats,and to provide basic guidance and new ideas for clinical treatment of NAFLD and liver cancer precancerous lesions.Methods Male SD rats were fed with a modified high yeast high fat diet to establish a model of high uric acid mediated nonalcoholic fatty liver disease in rats.72 rats,according to body weight were randomly assigned to six groups:normal control group(Group A),NAFLD group(Group B),NAFLD with high uric acid modeling group(Group C)and RES treatment group(Group D).Each group has 12 rats,and continuous administration for 12 weeks.The weight of rats,wet weight of liver,and expression of liver function,insulin,TNF-α,IL-6,FFA,MDA,SOD and GSH-PX were detected in rats’ serum.The expression of SIRT1,COX-2 and NF-κB were observed by immunohistochemistry.And the expression of SIRT1,FOXO3a and NF-κB mRNA were detected by reverse transcription PCR.Results(1)After resveratrol treatment,in the RES treatment group,the liver function significantly improved(P<0.01);in RES treatment group,SOD,GSH-PX levels corresponding model group,was significantly increased(P<0.01);and TNF-α,IL-6 and MDA levels compared with that in the model group decreased significantly(P<0.01).(2)Liver pathology showed that the fatty degeneration of liver tissue and the inflammatory reaction after resveratrol treatment were reduced compared with model group.(3)Immunohistochemistry results:compared with the model group,the expression of SIRT1 protein was significantly increased(P<0.01),COX-2,NF-κB protein expression was significantly decreased(P<0.01).There was a negative correlation between COX-2 and SIRT1(P<0.01);there was a negative correlation between SIRT1 and NF-κB(P<0.01);there was a positive correlation between COX-2 and NF-κB(P<0.01).There was a negative correlation between SIRT1 and liver tissue inflammation score(P<0.01).NF-κB,COX-2 and liver tissue inflammation score had positive correlation(P<0.01).(4)PCR results:after treatment,the expression of FOXO3a and SIRT1 mRNA in RES treatment group were higher than that in the model group(P<0.01).The expression of NF-κB mRNA in RES treatment group was lower than that in the model group(P<0.01).There was a positive correlation between FOXO3a and SIRT1(P<0.01);there was a negative correlation between SIRT1,FOX03a and NF-κB(P<0.01).There was a negative correlation between SIRT1 and the degree of liver inflammation score(P<0.01);between FOXO3a and the degree of liver inflammation scores had negative correlation(P<0.01);and there was a positive correlation between the NF-κB and liver tissue inflammation score(P<0.01).Conclusion(1)In this study,it was prompted that the changes of fat and inflammation in rat liver were related to the regulation of SIRT1,and the expression of SIRT1,COX-2,FOXO3a and NF-κB may involved in the occurrence and development of hepatic steatosis and inflammation.(2)This study showed that resveratrol plays a role in the treatment of NAFLD,it promoted SIRT1 expression in liver cells ofNAFLD accompanied by high levels of uric acid,promoting acetylation of PGC-1 and FOXO,inhibiting the activation of NF-κB,improving insulin resistance,inhibiting lipid peroxidation and reducing oxidative stress and liver inflammation.Resveratrol plays a role in the prevention of liver cancer precancerous lesions.