苯扎贝特治疗对高脂血症患者血浆低密度脂蛋白和高密度脂蛋白亚组分以及卵磷脂胆固醇酰基转移酶和胆固醇酯转移蛋白活性的影响。

Effects of bezafibrate therapy on subfractions of plasma low-density lipoprotein and high-density lipoprotein, and on activities of lecithin:cholesterol acyltransferase and cholesteryl ester transfer protein in patients with hyperlipoproteinemia.

作者信息

Homma Y, Ozawa H, Kobayashi T, Yamaguchi H, Sakane H, Mikami Y, Mikami Y, Nakamura H

机构信息

Department of Internal Medicine, Tokai University Oiso Hospital, Japan.

出版信息

Atherosclerosis. 1994 Apr;106(2):191-201. doi: 10.1016/0021-9150(94)90124-4.

DOI:10.1016/0021-9150(94)90124-4

PMID:8060379

Abstract

We investigated the effects of 12 weeks of bezafibrate treatment on plasma lipoprotein subfraction levels and on activities of LCAT and CETP in 25 patients with hyperlipoproteinemia. Bezafibrate reduced plasma levels of VLDL-TC and VLDL-TG by 69% and 66% (P < 0.001) and plasma levels of IDL-TC and IDL-TG were decreased by 37% and 31% (P < 0.01). Bezafibrate had no significant effects on plasma levels of LDL1 (1.019 < d < 1.045)-TC and LDL1-TG in the study population as a whole but significantly increased the plasma level of LDL1-TC in the subgroup of 9 patients with type IV hyperlipoproteinemia. Bezafibrate reduced plasma levels of LDL2 (1.045 < d < 1.063)-TC, LDL2-TG by 48% and 44% (P < 0.001) in both type II and type IV hyperlipoproteinemic patients. Gradient polyacrylamide gel electrophoresis revealed a decrease in small LDL particles. Bezafibrate did not affect the plasma level of HDL2-TC but reduced the HDL2-TG concentration significantly (P < 0.001). Bezafibrate increased the plasma level of HDL3-TC by 37% and reduced the HDL3-TG level significantly by 20% (P < 0.001). Gradient polyacrylamide gel electrophoresis revealed an increase in HDL3a and a decrease in HDL2a. Bezafibrate suppressed the activities of LCAT and CETP by 21% (P < 0.001) and 17% (P < 0.01), respectively. The bezafibrate-induced decrease in plasma levels of small, heavy LDL might be related to its inhibition of LCAT and CETP activities which resulted in suppression of heteroexchange of HDL-EC with triglyceride in large, light LDL. The bezafibrate-induced increase in large HDL3 (HDL3a) could not be explained solely by its suppression of LCAT and CETP activities. The decrease of plasma small, heavy LDL as well as TG-rich lipoproteins by bezafibrate seems to be beneficial for prevention of atherosclerotic diseases.

摘要

我们研究了25例高脂蛋白血症患者接受12周苯扎贝特治疗对血浆脂蛋白亚组分水平以及卵磷脂胆固醇酰基转移酶（LCAT）和胆固醇酯转运蛋白（CETP）活性的影响。苯扎贝特使极低密度脂蛋白胆固醇（VLDL-TC）和极低密度脂蛋白甘油三酯（VLDL-TG）的血浆水平分别降低了69%和66%（P<0.001），中间密度脂蛋白胆固醇（IDL-TC）和中间密度脂蛋白甘油三酯（IDL-TG）的血浆水平分别降低了37%和31%（P<0.01）。在整个研究人群中，苯扎贝特对低密度脂蛋白1（LDL1，1.019<d<1.045）-TC和LDL1-TG的血浆水平无显著影响，但在9例IV型高脂蛋白血症患者亚组中显著升高了LDL1-TC的血浆水平。在II型和IV型高脂蛋白血症患者中，苯扎贝特使低密度脂蛋白2（LDL2，1.045<d<1.063）-TC、LDL2-TG的血浆水平分别降低了48%和44%（P<0.001）。梯度聚丙烯酰胺凝胶电泳显示小LDL颗粒减少。苯扎贝特不影响高密度脂蛋白2（HDL2）-TC的血浆水平，但显著降低了HDL2-TG浓度（P<0.001）。苯扎贝特使高密度脂蛋白3（HDL3）-TC的血浆水平升高了37%，并显著降低了HDL3-TG水平20%（P<0.001）。梯度聚丙烯酰胺凝胶电泳显示HDL3a增加，HDL2a减少。苯扎贝特分别抑制LCAT和CETP的活性21%（P<0.001）和17%（P<0.01）。苯扎贝特引起的小而密LDL血浆水平降低可能与其对LCAT和CETP活性的抑制有关，这导致了HDL-EC与大而轻LDL中甘油三酯的异源性交换受到抑制。苯扎贝特引起的大HDL3（HDL3a）增加不能仅用其对LCAT和CETP活性的抑制来解释。苯扎贝特降低血浆中小而密LDL以及富含甘油三酯的脂蛋白水平似乎有利于预防动脉粥样硬化疾病。