The use of simvastatin for the prevention of gallstones in the lithogenic prairie dog model
The use of simvastatin for the prevention of gallstones in the lithogenic prairie dog model
复制标题
DOI：
10.1381/096089203322618678
复制
发表时间：
2003-12-01
期刊：
影响因子：
2.9
通讯作者：
Schriver, JP
中科院分区：
文献类型：
--
作者：
Davis, KG;Wertin, TM;Schriver, JP
背景：病态肥胖的手术正在迅速增加。接受减肥手术的患者在快速减肥过程中很容易出现胆结石。这些患者经常服用熊去氧胆酸等药物来预防胆结石形成；然而，患者通常对这些药物的耐受性较差，随后会停止使用。我们在成石动物模型中进行了一项研究，以评估潜在替代药物预防胆结石的有效性。方法：将 20 只雄性土拨鼠随机分为 2 组，并喂食成石饮食 28 天。研究组动物服用 2.5 毫克 HMG-CoA 还原酶抑制剂辛伐他汀。测量总胆固醇和甘油三酯，并在研究期结束时对每只动物进行开腹胆囊切除术。目视检查胆囊是否有胆结石和显微镜下胆汁胆固醇晶体形成。结果：与对照组相比，研究动物的总胆固醇降低了 36%。用辛伐他汀治疗的动物有 5/10 (50%) 的动物出现胆结石形成，而对照动物的比例为 6/10 (60%)。研究动物中 80% 出现了微观胆固醇晶体形成，与对照动物中发现的数量相同。结论：尽管辛伐他汀降低了胆固醇，但在此动物模型中，辛伐他汀既不能防止胆结石形成，也不能防止胆汁胆固醇晶体形成。鉴于减肥手术数量的迅速增加，加上熊去氧胆酸的耐受性差，应继续为这些患者寻找可行的替代方案。
Background: Surgery for morbid obesity is rapidly increasing. Patients undergoing bariatric surgery are prone to gallstone development during the rapid weight loss. These patients are often given medications such as ursodeoxycholic acid to prevent gallstone formation; however, these medications are often poorly tolerated by patients, who subsequently discontinue them. We performed a study in a lithogenic animal model to assess the effectiveness of a potential alternate medication for gallstone prevention.Methods: 20 male prairie dogs were randomly separated into 2 groups and fed a lithogenic diet for 28 days. The study group animals were given 2.5 mg of the HMG-CoA reductase inhibitor simvastatin. Total cholesterol and triglycerides were measured and an open cholecystectomy was performed on each animal at the conclusion of the study period. The gallbladder was visually inspected for gallstones and microscopic biliary cholesterol crystal formation.Results: There was a decrease of 36% in the total cholesterol of the study animals compared to controls. The animals treated with simvastatin showed gallstone formation in 5/10 (50%) of animals, compared with 6/10 (60%) of control animals. The study animals demonstrated microscopic cholesterol crystal formation in 80%, identical to the number found in the control animals.Conclusion: Despite a reduction in cholesterol, simvastatin prevented neither gallstone formation nor biliary cholesterol crystals in this animal model. Given the rapid increase in the number of bariatric surgical procedures coupled with the poor tolerance of ursodeoxycholic acid, viable alternatives should continue to be sought for these patients.