Liraglutide ameliorates liver injury of type 2 diabetic mice via micro-RNA-33-AMPK pathway / 中国病理生理杂志

ABSTRACT

AIM:To observe the effects of liraglutide on the level of microRNA-33 (miR-33) and the expres-sion of AMP-activated protein kinase ( AMPK ) and apoptosis-related proteins in mice with type 2 diabetes mellitus (T2DM), and to explore its possible mechanism .METHODS:High-fat diet and intraperitoneal injection of streptozocin were used to establish the type 2 diabetic model in C57BL/6 mice.The mice were randomly divided into 4 groups ( n=15 )in control group , the normal mice were subcutaneously injected with equivalent volume of saline ;in model group , the T2DM mice were subcutaneously injected with equivalent volume of saline ; in low-and high-dose liraglutide treatment groups, the T2DM mice were subcutaneously injected with 100 and 200 μg? kg -1? d-1, respectively.After 4 weeks of administration, the levels of FBG, TG, TC, HDL-C, LDL-C, ALT and AST were determined.HE staining was used to ob-serve the pathological changes of the liver tissues .The protein level of cleaved caspase-3 in the liver tissue was detected by the technique of immunofluorescence .The protein levels of p-AMPK/AMPK and apoptosis-related proteins were detected by Western blot .The expression of miR-33 in the liver tissues was detected by real-time PCR.RESULTS: Compared with model group, the contents of FBG, TG, TC, LDL-C, ALT and AST were decreased significantly , while the content of HDL-C was increased significantly in low-dose liraglutide group and high-dose liraglutide group ( P<0.05 ) .The protein levels of phosphorylated AMPK and Bcl-2 were up-regulated significantly , and the expression of cleaved caspase-3 was down-regulated significantly (P<0.05).The level of miR-33 was decreased significantly (P<0.01).CONCLUSION:Liraglutide alleviates liver injury in type 2 diabetic mice , and the mechanism may be associated with reducing the level of miR-33 and increasing the phosphorylation of AMPK in the liver tissues , thereby inhibiting hepatocyte apoptosis .