Hillebrant C G, Axelson M, Björkhem I, Wang F H, Nyberg B, Einarsson C
Karolinska Institute, Huddinge University Hospital, Stockholm, Sweden.
Eur J Clin Invest. 1998 Apr;28(4):324-8. doi: 10.1046/j.1365-2362.1998.00288.x.
HMG-CoA reductase inhibitors are now the therapy of choice in the treatment of hypercholesterolaemia. The effects of long-term treatment with these substances on plasma lipoproteins, cholesterol metabolism and biliary secretion of lipids have been extensively studied in humans. Much less is known about the effects of short-term treatment. The aim of this study was to determine the time course of the effects of HMG-CoA reductase inhibitors on plasma lipoprotein levels as well as cholesterol and bile acid synthesis in gallstone patients.
Thirty-six patients undergoing elective cholecystectomy were included in the study. Except for the gallstone disease, these patients were otherwise healthy. Four groups of subjects were treated with the HMG-CoA reductase inhibitor pravastatin (Pravachol), 20 mg twice daily for 12, 24, 48 and 72 h preoperatively. Plasma lipoproteins and plasma levels of lathosterol and 7 alpha-hydroxy-4-cholesten-3-one were determined before initiation of pravastatin treatment and on the morning of the day of the operation, lathosterol reflecting hepatic HMG-CoA reductase activity and 7 alpha-hydroxy-4-cholesten-3-one the activity of cholesterol 7 alpha-hydroxylase, the rate-determining enzyme in bile acid synthesis.
All treatment groups displayed a significant decrease in total cholesterol and low-density lipoprotein (LDL)-cholesterol, by about 12% and 17% respectively. Lathosterol was reduced by about 50% in all treatment groups. Of great interest was the finding that 7 alpha-hydroxy-4-cholesten-3-one was unaffected in all treatment groups.
The results show that short-term pravastatin treatment in gallstone patients rapidly inhibits cholesterol synthesis and lowers plasma LDL-cholesterol levels without effects on bile acid synthesis.
HMG-CoA还原酶抑制剂目前是治疗高胆固醇血症的首选疗法。这些物质长期治疗对人体血浆脂蛋白、胆固醇代谢及脂质胆汁分泌的影响已得到广泛研究。而关于短期治疗的效果了解较少。本研究的目的是确定HMG-CoA还原酶抑制剂对胆结石患者血浆脂蛋白水平以及胆固醇和胆汁酸合成影响的时间进程。
36例行择期胆囊切除术的患者纳入本研究。除胆结石疾病外，这些患者其他方面均健康。四组受试者在术前12、24、48和72小时接受HMG-CoA还原酶抑制剂普伐他汀（普拉固）治疗，每日两次，每次20mg。在开始普伐他汀治疗前及手术当天早晨测定血浆脂蛋白以及羊毛甾醇和7α-羟基-4-胆甾烯-3-酮的血浆水平，羊毛甾醇反映肝脏HMG-CoA还原酶活性而7α-羟基-4-胆甾烯-3-酮反映胆固醇7α-羟化酶活性，后者是胆汁酸合成中的限速酶。
所有治疗组的总胆固醇和低密度脂蛋白（LDL）胆固醇均显著降低，分别约降低12%和17%。所有治疗组的羊毛甾醇均降低约50%。一个非常有趣的发现是所有治疗组的7α-羟基-4-胆甾烯-3-酮均未受影响。
结果表明，胆结石患者短期普伐他汀治疗可迅速抑制胆固醇合成并降低血浆LDL胆固醇水平，而对胆汁酸合成无影响。
