The Study Of The Effects And The Mechanism Of Liver X Receptor Agonist And/or AMPK Activator On The Metabolism Of Lipids In A Mouse Model Of Hyperlipemia

ObjectiveTo study the effects and the mechanism of Liver X receptor agonist and/or metformin on the metabolism of lipids in a mouse model of hyperlipemia by gastric perfusion of intralipid.MethodsEstablish a mouse model of hyperlipemia by gastric perfusion of intralipid. Divided into five groups:placebo group, hyperlipemia group, T0901317 group, metformin group, T0901317 combine metformin group(combination group). After the administration of these drugs for 8 weeks,analyze serum lipid level by LX20 Beckman Coulter automated biochemical assay apparatus and detect the level of SREBP1-c, AMPK and AMPK-P by Immunochistochemistry and Western blot.Results1,As compared with the placebo group, the hyperlipemia group had higher serum levels of total cholesterol (p<0.05), triglyceride (p<0.05) and low-density lipoprotein cholesterol (p<0.05). The expression level of SREBP1-c is higher in the hyperlipemia group (p<0.05). However, there is no significant difference in serum levels of high-density lipoprotein cholesterol and the expression of AMPK and AMPK-P between these two groups(p>0.05).2,There is no significant difference in serum levels of lipids between the metformin group and the hyperlipemia group(p>0.05). There is no significant difference in expression levels of AMPK, however, there is markedly increasing in the expression of AMPK-P and SREBP1-c.3,As compared with the hyperlipemia group both the serum level of high density lipoprotein cholesterol and triglyceride in the T0901317 group are significantly increased (p<0.05),as well as the expression of SREBP1-c in the hepatic cell. Both the serum level of total cholesterol and low density lipoprotein cholesterol in the T0901317 group are significantly decreased ( p<0.05),as well as the expression of AMPK-P. However, there in no significant difference in expression levels of AMPK in these two group.4,In combination group, the serum level of high density lipoprotein cholesterol remains increasing, however, the serum level of triglyceride is significantly lower than that of T0901317 group (p<0.05). The expression of AMPK-P is higher, however, the expression of SREBP1-c is lower, than that of T0901317 group (p<0.05). There in no significant difference in expression levels of AMPK in these two group.5,As compared with the hyperlipemia group both the serum level of low density lipoprotein cholesterol, total cholesterol and triglyceride in the combination group are significantly decreased (p<0.05),as well as the expression of SREBP1-c in the hepatic cell. The serum level of high density lipoprotein cholesterol in the combination group are significantly increased ( p<0.05),as well as the expression of AMPK-P. However, there in no significant difference in expression levels of AMPK in these two group.Conclusion1,The high serum level of triglyceride induced by T0901317 can be inhibited by metformin in a mouse model of hyperlipemia by gastric perfusion of intralipid.2,The activation of AMPK by metformin inhibit the up-regulation of SREBP1-c by T0901317. The down-regulation of SREBP1-c reduce the high level of triglyceride which induce by T0901317, the liver X receptor.