Crosignani Andrea, Del Puppo Marina, Longo Matteo, De Fabiani Emma, Caruso Donatella, Zuin Massimo, Podda Mauro, Javitt Norman B, Kienle Marzia Galli
Department of Medicine, Surgery and Dentistry, School of Medicine San Paolo, Italy.
Clin Chim Acta. 2007 Jul;382(1-2):82-8. doi: 10.1016/j.cca.2007.03.025. Epub 2007 Apr 12.
Cholesterol elimination occurs through bile acid synthesis that starts within the liver from 7alpha-hydroxylation or in extrahepatic tissues from 27-hydroxylation. This study was aimed at investigating in vivo these two pathways in patients with chronic liver disease.
Serum concentrations of 7alpha- and 27-hydroxycholesterol were measured in 54 patients (29 with primary biliary cirrhosis and 25 with chronic hepatitis C) and 18 controls. The rate of oxysterol plasma appearance was calculated after intravenous infusions of deuterated 7alpha- and 27-hydroxycholesterol in patients (n=8) and control subjects (n=8) who gave consent. The expression of sterol 27-hydroxylase was evaluated in macrophages isolated from 20 subjects.
In patients with liver disease, the rate of plasma appearance of 7alpha-hydroxycholesterol was significantly reduced (1.44+/-0.96 vs. 2.75+/-1.43 mg/hour, p=0.03), the degree of reduction being related with the severity of the disease (p=0.01) whereas that of 27-hydroxycholesterol was unaffected. The rate of plasma appearance of 27-hydroxycholesterol was significantly related to its serum concentrations (r=0.54, p=0.03) and to its release from cultured macrophages ( r=0.85, p=0.03).
In liver disease 7alpha-hydroxylation of cholesterol seems to be impaired while 27-hydroxylation is unaffected. Serum concentrations of 27-hydroxycholesterol are useful to obtain information on the activity of this alternative pathway.
胆固醇的清除通过胆汁酸合成来实现，该过程始于肝脏内的7α-羟化作用或肝外组织中的27-羟化作用。本研究旨在对慢性肝病患者体内的这两条途径进行研究。
测定了54例患者（29例原发性胆汁性肝硬化患者和25例慢性丙型肝炎患者）及18例对照者血清中7α-和27-羟胆固醇的浓度。在同意参与的患者（n = 8）和对照者（n = 8）静脉输注氘代7α-和27-羟胆固醇后，计算氧甾醇血浆出现率。对从20名受试者分离出的巨噬细胞中甾醇27-羟化酶的表达进行了评估。
在肝病患者中，7α-羟胆固醇的血浆出现率显著降低（1.44±0.96 vs. 2.75±1.43 mg/小时，p = 0.03），降低程度与疾病严重程度相关（p = 0.01），而27-羟胆固醇的血浆出现率未受影响。27-羟胆固醇的血浆出现率与其血清浓度显著相关（r = 0.54，p = 0.03），并与其从培养的巨噬细胞中的释放相关（r = 0.85，p = 0.03）。
在肝病中，胆固醇的7α-羟化作用似乎受损，而27-羟化作用未受影响。27-羟胆固醇的血清浓度有助于获取有关这一替代途径活性的信息。
