Tazuma S, Kajiyama G, Mizuno T, Yamashita G, Miura H, Kajihara T, Hattori Y, Miyake H, Nishioka T, Hyogo H, Sunami Y, Yasumiba S, Ochi H, Matsumoto T, Abe A, Adachi K, Omata F, Ueno F, Sugata F, Ohguri S, Shibata H, Kokubu S
First Department of Internal Medicine, Hiroshima University School of Medicine, Japan.
J Clin Gastroenterol. 1998 Jun;26(4):287-91. doi: 10.1097/00004836-199806000-00015.
Inhibitors of 3-hydroxy,3-methylglutaryl coenzyme A (HMG-CoA) reductase have been reported to decrease the cholesterol saturation index (CSI) in duodenal bile in humans and to prevent formation of cholesterol gallstones in animal studies. We performed a prospective study to evaluate the role of HMG-CoA reductase inhibitors as gallstone-dissolving agents. Fifty patients with radiolucent gallstones in a gallbladder opacifying at drip infusion cholecystography were treated with either 10 mg/day simvastatin plus 600 mg/day ursodeoxycholic acid (group 1, n=26) or 600 mg/day ursodeoxycholic acid alone (group 2, n=24) for 12 months. The ratio of solitary to multiple gallstone cases was 21:29. Plasma lipid levels were assessed and ultrasonographic examination of the gallbladder was performed at baseline and at 3-month intervals during treatment. Duodenal bile sampling was performed in five patients in each group at baseline and after 12 months of treatment. Plasma cholesterol decreased significantly in group 1 but not in group 2. In solitary gallstone cases, no significant difference in dissolution rates was observed between groups 1 (3 of 9, 33%) and 2 (4 of 12, 33%). In contrast, the dissolution rate in multiple gallstone cases was significantly higher in group 1 (12 of 17, 71%) than in group 2 (3 of 12, 25%) (p < 0.01). Bile cholesterol saturation index was significantly decreased (p < 0.01) but did not significantly differ between the two groups. These results suggest that combination therapy with simvastatin and ursodeoxycholic acid is more effective for cholesterol gallstone dissolution than ursodeoxycholic acid monotherapy in patients with multiple gallstones.
据报道，3-羟基-3-甲基戊二酰辅酶A（HMG-CoA）还原酶抑制剂可降低人体十二指肠胆汁中的胆固醇饱和指数（CSI），并在动物研究中预防胆固醇胆结石的形成。我们进行了一项前瞻性研究，以评估HMG-CoA还原酶抑制剂作为胆结石溶解剂的作用。50例在静脉滴注胆囊造影时胆囊显影的胆囊内有透X线胆结石的患者，接受了为期12个月的治疗，其中一组（第1组，n = 26）给予每日10 mg辛伐他汀加每日600 mg熊去氧胆酸，另一组（第2组，n = 24）仅给予每日600 mg熊去氧胆酸。单发与多发胆结石病例的比例为21:29。在基线时以及治疗期间每3个月进行一次血脂水平评估和胆囊超声检查。每组各5例患者在基线时和治疗12个月后进行十二指肠胆汁采样。第1组血浆胆固醇显著降低，而第2组未降低。在单发胆结石病例中，第1组（9例中的3例，33%）和第2组（12例中的4例，33%）的溶解率无显著差异。相比之下，第1组多发胆结石病例的溶解率（17例中的12例，71%）显著高于第2组（12例中的3例，25%）（p < 0.01）。胆汁胆固醇饱和指数显著降低（p < 0.01），但两组之间无显著差异。这些结果表明，对于多发胆结石患者，辛伐他汀和熊去氧胆酸联合治疗比熊去氧胆酸单药治疗在胆固醇胆结石溶解方面更有效。
