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胆固醇结石病中的肝脏胆固醇代谢

Hepatic cholesterol metabolism in cholesterol gallstone disease.

作者信息

Reihnér E, Angelin B, Björkhem I, Einarsson K

机构信息

Department of Surgery, Karolinska Institutet, Huddinge University Hospital, Sweden.

出版信息

J Lipid Res. 1991 Mar;32(3):469-75.

PMID:2066675
Abstract

Hepatic cholesterol metabolism was examined in 27 Swedish patients with cholesterol gallstone disease and in 13 patients free of gallstones operated for roentgenographically suspect polyps in the gallbladder. All 40 patients underwent cholecystectomy, and a liver biopsy and gallbladder bile were obtained at surgery. The cholesterol saturation of gallbladder bile was significantly higher in patients with gallstones compared to the gallstone-free controls (131 +/- 13 vs. 75 +/- 5%, P less than 0.001). Microsomal 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity, governing cholesterol synthesis, did not differ between gallstone and gallstone-free patients (104 +/- 11 vs. and 109 +/- 22 pmol/min per mg protein, respectively). The activity of cholesterol 7 alpha-hydroxylase, catalyzing the catabolism of cholesterol to bile acids, was not significantly decreased in gallstone patients (6.2 +/- 1.1 vs. 8.0 +/- 2.0 pmol/min per mg protein). The capacity to esterify cholesterol, judged by the activity of acyl coenzyme A:cholesterol acyltransferase (ACAT), was similar in gallstone and gallstone-free patients (5.4 +/- 0.4 vs. 6.7 +/- 1.1 pmol/min per mg protein). In the presence of exogenous cholesterol, ACAT activity increased by more than fourfold in both groups. No correlation was found between the saturation of gallbladder bile and any of the mentioned enzyme activities in gallstone patients. It is concluded that distinct abnormalities in cholesterol metabolizing enzymes are not of major importance for development of gallstones in Swedish patients with cholesterol gallstone disease. The results support the contention that the etiology of cholesterol gallstones is multifactorial.

摘要

对27例患有胆固醇性胆结石疾病的瑞典患者以及13例因胆囊内有X线检查怀疑的息肉而接受手术且无胆结石的患者进行了肝脏胆固醇代谢检查。所有40例患者均接受了胆囊切除术,并在手术时获取了肝活检组织和胆囊胆汁。与无胆结石的对照组相比,胆结石患者胆囊胆汁的胆固醇饱和度显著更高(分别为131±13%和75±5%,P<0.001)。控制胆固醇合成的微粒体3-羟基-3-甲基戊二酰辅酶A(HMG-CoA)还原酶活性在胆结石患者和无胆结石患者之间没有差异(分别为104±11和109±22 pmol/分钟每毫克蛋白质)。催化胆固醇分解为胆汁酸的胆固醇7α-羟化酶活性在胆结石患者中没有显著降低(分别为6.2±1.1和8.0±2.0 pmol/分钟每毫克蛋白质)。通过酰基辅酶A:胆固醇酰基转移酶(ACAT)活性判断的胆固醇酯化能力在胆结石患者和无胆结石患者中相似(分别为5.4±0.4和6.7±1.1 pmol/分钟每毫克蛋白质)。在存在外源性胆固醇的情况下,两组的ACAT活性均增加了四倍以上。在胆结石患者中,未发现胆囊胆汁饱和度与上述任何酶活性之间存在相关性。结论是,在患有胆固醇性胆结石疾病的瑞典患者中,胆固醇代谢酶的明显异常对于胆结石的形成并不重要。这些结果支持了胆固醇性胆结石病因是多因素的这一观点。

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