title: Ursodeoxycholic acid lowers bile lithogenicity by regulating SCP2 expression in rabbit cholesterol gallstone models.
abstract: Aims:We designed this study to get insight into the disorder of lipid metabolism during cholesterol gallstone formation and evaluate the effect of ursodeoxycholic acid on the improvement of bile lithogenicity and on expression of lipid related genes.Methods: Rabbit cholesterol gallstone models were induced by high cholesterol diet. Bile, blood and liver tissues were obtained from rabbits after 0, 1, 2, 3, 4 and 5 weeks. Bile and blood lipids were measured enzymatically. 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), cytochrome P450, family 7, subfamily A, polypeptide 1 (CYP7A1) and sterol carrier protein 2 (SCP2) mRNA expressions were detected by using quantitative real-time RT-PCR. Cholesterol saturation index (CSI) was calculated by using Carey table to represent the bile lithogenicity.Results:Rates of gallstone formation of the 4 and 5 week treatment groups were 100 %, but that of the ursodeoxycholic acid treatment group was only 33.3 %. Expression of HMGCR and SCP2 mRNA in the 4 week group was upregulated and that of CYP7A1 mRNA decreased as compared with the 0 week group. Ursodeoxycholic acid could significantly extend nucleation time of bile and lower CSI. Ursodeoxycholic acid could reduce the expression of SCP2, but couldn't influence expression of HMGCR and CYP7A1.Conclusions:Abnormal expression of HMGCR, CYP7A1 and SCP2 might lead to high lithogenicity of bile. Ursodeoxycholic acid could improve bile lipids and lower bile lithogenicity, thereby reducing the incidence of gallstones. So it might be a good preventive drug for cholesterol gallstones.
authors.affiliation: Department of Surgery, Tianjin Nankai Hospital, Nankai Clinical School of Medicine, Tianjin Medical University, 122 Sanwei Road Nankai District, Tianjin 300100, China.
authors.forename: Yunfeng
authors.initials: Y
authors.lastname: Cui
authors.affiliation: Department of Surgery, Tianjin Nankai Hospital, Nankai Clinical School of Medicine, Tianjin Medical University, 122 Sanwei Road Nankai District, Tianjin 300100, China.
authors.forename: Zhonglian
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Surgery, Tianjin Nankai Hospital, Nankai Clinical School of Medicine, Tianjin Medical University, 122 Sanwei Road Nankai District, Tianjin 300100, China.
authors.forename: Erpeng
authors.initials: E
authors.lastname: Zhao
authors.affiliation: Institute of Molecular Biology, Nankai University, 94 Weijin Road Nankai District, Tianjin 300071, China.
authors.forename: Ju
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Surgery, Tianjin Nankai Hospital, Nankai Clinical School of Medicine, Tianjin Medical University, 122 Sanwei Road Nankai District, Tianjin 300100, China.
authors.forename: Naiqiang
authors.initials: N
authors.lastname: Cui
keywords: CSI; CYP7A1; HMGCR; SCP2 mRNA; bile lipids; cholesterol gallstones; rabbit models