Experimental Study On The Effect Of H8 On The Enzymes Involved In Fat Synthesis And Decomposition Of 11?-HSD1 Gene Overexpressing Mice

Objective:The effects of curcumin analogues H8 on the expression of 11?-HSD1gene overexpression in mice were investigated by overexpression of 11?-HSD1 gene.Methods:A new pLVX-EF1alpha-IRES-Zs Green1-Ms11?-HSD1 vector was constructed by molecular biology techniques.293T cells were cultured and transfected with lentivirus to collect the virus solution.64 male C57BL/6 mice were randomly divided into 4 groups:normal control group,normal administration group,model group and model administration group.The mice were overexpressed with the lentiviral vector 11?-HSD1gene and the mice were overexpressed with curcumin analogues H8(0.5 mg·kg^-1·d^-1)for2 months.Measure the weight and diet of all experimental mice once a week.After 2months,the glucose tolerance and insulin tolerance were measured.Blood samples were taken from the eyes and blood samples were taken to detect changes in biochemical indexes in mice serum:FFA,GLU,HDL,LDL,TC,TG.The histopathological changes and fibrosis were observed by HE staining,Sirius red staining and Masson staining.The mRNA expression of acc1,acc2,cpt-1,srebp-1,fas and hsl in mouse liver tissue was detected by real-time PCR.The expression of related protein was observed by immunohistochemistry.Results:The body weight of the mice was significantly higher than that of the control group.After treatment with H8,the body weight of the mice in the treatment group was significantly lower than that in the model group,and the insulin resistance in the model group was significantly decreased.The levels of FFA,GLU and LDL in the model group were significantly higher than those in the control group?P<0.05,P<0.01?.,and the levels of FFA,GLU and LDL were significantly decreased?P<0.05?.Degeneration and necrosis,cell infiltration,after H8 treatment,inflammation reduced,clear organizational structure,necrosis and infiltration was significantly improved.The levels of acc1,acc2,srebp-1,fas and hsl in the liver of the model group were significantly higher than those in the control group?P<0.05?.The levels of acc1,acc2,srebp-1,fas and hsl in the model group were significantly higher than those in the control group?P<0.05??P<0.01?,the level of cpt-1gene was significantly decreased?P<0.01?,and the mRNA expression of acc1,acc2,srebp-1,fas and hsl was significantly decreased after H8 treatment?P<0.05,P<0.01,P<0.001?,cpt-1 gene level was significantly increased?P<0.05?,The levels of ACC1,ACC2 and HSL in the immunohistochemical model group were significantly higher than those in the control group,and the AMPK protein was significantly lower than that of the control group.After treatment with H8,the levels of ACC1,ACC2 and HSL were significantly decreased and the AMPK protein was significantly increased.Conclusion:The overexpression of 11?-HSD1 gene can lead to lipid metabolism disorder.Curcumin analogues H8 can improve the lipid metabolism disorder of overexpression of 11?-HSD1 gene in mice.The mechanism may be related to the improvement of ACC1,ACC2,CPT-1,SREBP-1,FAS,HSL gene levels and protein levels.