Abstract: Objective To investigate the effects and mechanism of miR-29b on the cholesterol synthesis in the liver of hypercholesterolemia mice. Methods C57/BL6 mice were divided into 6 groups: 10 in control group was fed with normal diet, 10 in HF group was fed with Paigen diet, 6 in Con+shRNA group, 6 in Con+antago group, 6 in HF+shRNA group and 6 in HF+antago group. The Con+shRNA group and HF+shRNA group were injected with scrambled shRNA (2.5 mg/kg); Con+antago group and HF+antago group were injected with miR-29b antagomir (2.5 mg/kg). Total cholesterol in the plasma and liver was measured after 8 weeks. RT-qPCR was used to detect expression of miR-29b and SIRT1. Western blot was used to detect the expression of proteins relating cholesterol synthesis in the liver. Results 1) Compared with the control group, the HF group showed increased expression of miR-29b in the plasma and liver. 2) Compared with the HF+shRNA group, the total cholesterol in the plasma and liver of the HF+antago group decreased. miR-29b antagomir increased SIRT1 mRNA and protein expression in the liver. Along with elevated SIRT1 expression, SREBP2 mRNA and protein expression were decreased. Consistently, the expression of HMGCR was reduced by miR-29b antagomir. Conclusions The expres- sion of miR-29b is increased in liver tissue of hypercholesterolemia mice and miR-29b inhibitor can reduce cholesterol synthesis in the liver.

Key words: miR-29b, cholesterol synthesis, SIRT1