| Objective: To study the protective effect of Paeonal(Pae)on high-fat-induced nonalcoholic fatty liver disease(NAFLD)in rats,and to discuss the mechanism of NAFLD by regulating the activation of NLRP3 Inflammasome pathway,to provide reference for the clinical treatment of NAFLD and the further study of the mechanism of the action of Pae.Methods: The 60 SD rats were randomly divided into 6 groups with high dose of Pae(300 mg/kg),medium dose of Pae(200 mg/kg),low dose of Pae(100 mg/kg),Silymarin(100 mg/kg)positive control group,model group and normal group,with 10 of them each.Rats NAFLD model was obtained after 10 weeks of gastric lavage with high-fat emulsion in the remaining 5 groups except normal group.Then the model rats were given a high dose of Pae and a medium dose of Pae and a low dose of Pae and Silymarin for 4 weeks respectively,it was compared with normal group and model group.Observe the state of rats in each group.After the last dose of 24 H,chloral hydrate was injected intraperitoneally to anesthetize the rat.The liver was taken out and weighed,and the liver index was calculated.The liver tissue of rats was fixed with 10 % formalin solution,after 24 H,block sampling,dewatering and drying,embedded section.Sections were stained with HE method to observe the pathological changes under microscope.Took blood from the abdominal aorta,separated the serum,and determined the serum of aspartate transaminase(AST),alanine aminotransferase(ALT),triglyceride(TG),total cholesterol(TC),low density lipoprotein cholesterol(LDL-c),high density lipoprotein cholesterol(HDL-c),malondialdehyde(MDA),free fatty acid(FFA).Extracted protein from liver tissue to measure the protein expression level of NLRP3 and Caspase-1 in liver tissue of rats in each group by Western Blotting method.The changes of IL-1 beta and IL-18 were also measured.Results: All the indicators of Pae group were better than those of the model group.1.Pae improved the general condition of NAFLD rats.2.Pae improved the pathological morphology of NAFLD rats,and liver pathological section showed that the liver lesion of the Pae group was improved to different degrees.3.Pae improved liver function in NAFLD rats and had protective effects on hepatocytd.Pae lowered blood biochemical AST and ALT(P< 0.05).4.Pae improved lipid metabolism in NAFLD rats.Pae had an effect on the blood biochemical triglyceride(TG)(P<0.05),total cholesterol(TC),low density lipoprotein cholesterol(LDL-c)and high density lipoprotein cholesterol(HDL-c)(P<0.05)in the high fat induced NAFLD rats.5.Pae improved the stress of hepatic oxidative in NAFLD rats.There were significant differences between the MDA and FFA of Pae group and model group(P<0.01).6.Pae had protective effect on NAFLD in rats,and the Pae high-dose group had better effect.The effect of Pae high-dose group was better than that of the low-dose Pae group,which was similar to that of Silymarin group.7.Pae inhibited the activity of NLRP3 Inflammasome in NAFLD rats,and the Pae group has a significant effect on the protein expression of NLRP3 and Caspase-1 and downstream effect factors IL-1?and IL-18 in hepatocytes of NAFLD rats(P<0.01).Conclusion: Pae can protect high-fat-induced NAFLD model,which can obviously improve the general state,biochemical index,histopathological lesion and reduce the infiltration of inflammatory cells.The best effect of Pae on rats with NAFLD is high dose(300 mg/kg).The mechanism of Pae may be related to the decrease of the activity of NLRP3 Inflammasome and the down-regulation of IL-1?and IL-18 in the downstream factors. |
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