Effect of beta-muricholic acid on the prevention and dissolution of cholesterol gallstones in C57L/J mice.

Effect of beta-muricholic acid on the prevention and dissolution of cholesterol gallstones in C57L/J mice.
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DOI:
10.1194/jlr.m200297-jlr200
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发表时间:
2002-11
影响因子:
6.5
通讯作者:
D. Q. Wang;S. Tazuma
D. Q. Wang;S. Tazuma
中科院分区:
生物学2区
文献类型:
--
作者:
D. Q. Wang;S. Tazuma

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本研究探讨了啮齿类动物的一种天然的三羟基亲水性胆汁酸为了进行预防胆结石的研究,用致石饲料(2%胆固醇和0.5%胆酸)加或不加0.5%UDCA或β-鼠李酸,饲养8周的雄性C57L小鼠。在胆结石溶解研究中,另外几组形成胆结石的小鼠被喂食含或不含0.5%β-鼠胆酸或UDCA的食物8周。100%喂食致石饮食的小鼠形成胆固醇胆结石。添加β-鼠李酸和UDCA可显著降低胆汁分泌率、饱和指数和肠道对胆固醇的吸收,从而将胆结石患病率降低到20%和50%,并导致相界移动和E区扩大,从而防止胆固醇从液晶相转变为固体晶体和结石。服用8周的β-鼠李酸和UDCA组大鼠的胆结石完全消退率分别为100%和60%,而饮食组(10%)的胆结石完全消失率为60%。我们的结论是,在治疗或预防饮食诱导的或实验性的小鼠胆固醇结石方面,β-鼠李酸比UDCA更有效。
This study investigated whether beta-muricholic acid, a natural trihydroxy hydrophilic bile acid of rodents, acts as a biliary cholesterol-desaturating agent to prevent cholesterol gallstones and if it facilitates the dissolution of gallstones compared with ursodeoxycholic acid (UDCA). For gallstone prevention study, gallstone-susceptible male C57L mice were fed 8 weeks with a lithogenic diet (2% cholesterol and 0.5% cholic acid) with or without 0.5% UDCA or beta-muricholic acid. For gallstone dissolution study, additional groups of mice that have formed gallstones were fed chow with or without 0.5% beta-muricholic acid or UDCA for 8 weeks. One hundred percent of mice fed the lithogenic diet formed cholesterol gallstones. Addition of beta-muricholic acid and UDCA decreased gallstone prevalence to 20% and 50% through significantly reducing biliary secretion rate, saturation index, and intestinal absorption of cholesterol, as well as inducing phase boundary shift and an enlarged Region E that prevented the transition of cholesterol from its liquid crystalline phase to solid crystals and stones. Eight weeks of beta-muricholic acid and UDCA administration produced complete gallstone dissolution rates of 100% and 60% compared with the chow (10%). We conclude that beta-muricholic acid is more effective than UDCA in treating or preventing diet-induced or experimental cholesterol gallstones in mice.