Experimental Study On Role Of Cannabinoid Receptor1in Non-alcoholic Fatty Liver Disease Among Rats

Objective:Dynamic observation the expression of endogenous cannabinoid receptor1(CB1) in rats with non-alcoholic fatty liver disease (NAFLD) and study the effects of rimonabant, an CB1antagonist, on NAFLD. Hoping that CB1antagonist could be an alternative for early prevention and treatment of NAFLD.Methods:48healthy male SD rats were random divided into three groups:normal control group (normal feed); Model group (lard10%, cholesterol2%, egg yolk powder5%, propyl thiouracil0.2%, sucrose10%,based feed72.8%);Rimonabant group (model plus intraperitoneal injection rimonabant). At4and8weekend, eight rats of each group were executed, and the liver index, serum ALT、TG、TC and serum leptin, TNF-α were evaluated. The CB1receptor expression were studied by immunhist chemical staining at different stages of liver tissue.Results:(1)The weight and liver index of model group rats is significantly higher than the control group and the rimonabant group, the difference was significant (P<0.05);(2) Compared with the control group, the serum of ALT, TG, TC, TNF-α and Leptin levels were increased significantly in model group (P<0.05); but no difference been found between the control and the rimonabant group(p>0.05);(3) liver tissue changes including the visible liver cell enlargement, formation of lipid droplets and inflammatory cell infiltration were gradually increased in the model, especially in the model of8weeks. At the same period the liver lesions were alleviate in the rimonabant group;(4)Immunohistochemical detection of liver CB1receptors: the control group was negative; Both the model and Rimonabant group were positive but the density value of model group was much higher than the same period of rimonabant group, the difference was statistically significant (P<0.05);(5)Linear regression analysis results:liver CB1receptor and leptin and TNF-α was positively correlated (rleptin=0.755,rTNF-α=0.503,P<0.05). Conclusion:Endogenous cannabinoid CB1receptors play an important role in the development of NAFLD. Leptin and TNF-a may cooperate with CB1receptors to promote the continuous progress of non-alcoholic fatty liver disease.Specificity of CB1receptor antagonist may be available to prevent the formation and development of NAFLD.