Ezetimibe prevented cholesterol gallstone formation in mice fed with lithogenic diet

doi:10.16139/j.1007-9610.2018.01.010

Abstract

Abstract: Objective To investigate the effect of prevention on cholesterol gallstone formation by ezetimibe (Eze) in mice. Methods Thirty adult male C57BL/6 mice were randomly divided into three groups, fed with chow diet (chow group), lithogenic diet (LD group) and lithogenic diet with 5 mg/ (kg·d) ezetimibe by oral gavage (Eze group) for 8 weeks. On sacrifice, occurrence of gallstone was observed. Serum, liver, intestine and gallbladder were collected from each mouse. The serum lipids, hepatic cholesterol and biliary lipid composition were quantified by enzymatic methods. Expression of genes involved in metabolism of cholesterol in liver and intestines were measured by real-time quantitative PCR. Results No gallstone was observed in chow group. All mice formed gallstone in LD group (100%). No gallstone was formed in Eze group also. The intestinal cholesterol absorption rate in Eze group (9.29%±4.32%) significantly reduced when compared with LD group (58.62%±3.10%) and chow group (56.42%±2.67%) (P<0.01). Serum cholesterol level and hepatic cholesterol level in LD group [(4.99±0.50) mmol/L and (22.92±2.39) mg/g] increased markedly compared with chow group [(2.87±0.06) mmol/L and (2.45±0.08) mg/g] (P<0.05). Eze group lowered both serum cholesterol level [(1.11±0.10) mmol/L] and hepatic cholesterol level [(2.70±0.07) mg/g] compared with LD group(P<0.05). LD group has significantly higher biliary cholesterol content [LD group (10.87±1.46) mmol/L vs chow group (3.67±0.58) mmol/L] and cholesterol saturation index (CSI) [LD group:(1.42±0.19) vs chow group：(0.59±0.02)]. Biliary cholesterol content [(2.72±0.29) mmol/L] and CSI (0.57±0.07) in Eze group decreased markedly compared with LD group (P<0.01). Conclusions Eze could prevent cholesterol gallstone formation in mice through inhibition of intestinal cholesterol absorption.

Key words: Ezetimibe, Cholesterol gallstone disease, Intestine

CLC Number:

R657.4⁺2

WANG Qihan, SUN Haidong, CAI Qu, HU Hai, HAN Tianquan, JIANG Zhaoyan. Ezetimibe prevented cholesterol gallstone formation in mice fed with lithogenic diet[J]. Journal of Surgery Concepts & Practice, 2018, 23(01): 41-47.

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