Vessby B, Lithell H
Department of Geriatrics, Uppsala University, Sweden.
Atherosclerosis. 1990 May;82(1-2):137-43. doi: 10.1016/0021-9150(90)90152-9.
When bezafibrate therapy was interrupted in patients who had been on continuous treatment for hyperlipoproteinemia for 4-10 years, there were significant increases in the serum cholesterol, triglyceride and apolipoprotein B concentrations corresponding to an increase of the very low density lipoprotein (VLDL) levels by approximately 50%. This increase of VLDL was accompanied by reduced levels of the post-heparin lipoprotein lipase activity (LPLA) (P = 0.07) and hepatic lipase (P = 0.05) activity with a significant reduction of the skeletal muscle LPLA (P less than 0.05), but not the adipose tissue LPLA, and a retarded removal of an i v injected fat emulsion (P less than 0.01). There were no significant changes of the low or high density lipoprotein cholesterol or the apolipoprotein A-I or A-II concentrations. Three months after bezafibrate treatment the content of linoleic and gammalinoleic acid in the plasma cholesterol ester had increased significantly, while the palmitoleic and oleic acids were reduced in spite of unchanged dietary treatment. Taken together, the data indicate that a lipid-lowering effect of bezafibrate, particularly on the VLDL lipids, is maintained throughout long treatment periods. One mechanism for the reduced level of the triglyceride-rich lipoproteins is an increased activity of the lipoprotein-lipase activity in the skeletal muscle, which decreased when the treatment was interrupted. The significance of the changes of the plasma lipid fatty acid spectrum during bezafibrate treatment remains unclear.
在接受了4至10年高脂蛋白血症持续治疗的患者中,当停用苯扎贝特治疗时,血清胆固醇、甘油三酯和载脂蛋白B浓度显著升高,同时极低密度脂蛋白(VLDL)水平升高约50%。VLDL的这种升高伴随着肝素后脂蛋白脂肪酶活性(LPLA)(P = 0.07)和肝脂肪酶活性(P = 0.05)降低,骨骼肌LPLA显著降低(P < 0.05),但脂肪组织LPLA未降低,静脉注射脂肪乳剂的清除延迟(P < 0.01)。低密度或高密度脂蛋白胆固醇、载脂蛋白A-I或A-II浓度无显著变化。苯扎贝特治疗三个月后,血浆胆固醇酯中亚油酸和γ-亚麻酸含量显著增加,尽管饮食治疗不变,但棕榈油酸和油酸含量降低。综上所述,数据表明苯扎贝特的降脂作用,特别是对VLDL脂质的作用,在整个长期治疗期间得以维持。富含甘油三酯的脂蛋白水平降低的一种机制是骨骼肌中脂蛋白脂肪酶活性增加,治疗中断时该活性降低。苯扎贝特治疗期间血浆脂质脂肪酸谱变化的意义尚不清楚。