Bröijersen A, Eriksson M, Wiman B, Angelin B, Hjemdahl P
Department of Clinical Pharmacology, Karolinska Hospital, Stockholm, Sweden.
Arterioscler Thromb Vasc Biol. 1996 Apr;16(4):511-6. doi: 10.1161/01.atv.16.4.511.
Hypertriglyceridemia is linked to impaired fibrinolytic function, and lipid-lowering treatment with fibric acid derivatives could hypothetically improve fibrinolysis in this condition. We therefore conducted a double-blind, placebo-controlled, crossover study of gemfibrozil treatment on fibrinolytic function in 21 men with combined hyperlipoproteinemia. Measurements were performed at rest and during mental stress and after venous occlusion. The patients had clearly disturbed fibrinolytic function, with elevated plasminogen activator inhibitor-1 (PAI-1) activity at rest ( approximately 25 U/mL; reference, <15 U/mL). Gemfibrozil reduced plasma total and VLDL cholesterol as well as all triglyceride fractions, whereas HDL cholesterol increased (P <.001 for all). Total triglyceride levels were reduced by 57 +/- 4% (from 5.3 to 2.1 mmol/L). Fasting serum insulin levels were not altered by gemfibrozil treatment. Plasma levels of PAI-1 activity and tissue-type plasminogen activator (TPA) activity or antigen were unaffected by gemfibrozil treatment both at rest and during the provocations. The levels of D-dimer, plasmin/antiplasmin complex, and fibrinogen were also uninfluenced by gemfibrozil treatment. Mental stress elevated plasma TPA (P=.0036) and lowered PAI-1 (P=.0012) activity during placebo but not gemfibrozil treatment (P=.28 and P=.17, respectively), but treatment effects did not differ by ANOVA on delta values (ie, stress minus rest). Venous occlusion reduced PAI-1 activity, whereas TPA and plasmin/antiplasmin complex increased during both treatments. Thus, gemfibrozil treatment did not improve fibrinolysis or lower fibrinogen levels in men with combined hyperlipoproteinemia despite marked reduction of plasma triglyceride levels. It seems unlikely that improved fibrinolysis explains the primary preventive effect of gemfibrozil.
高甘油三酯血症与纤溶功能受损有关，理论上用纤维酸衍生物进行降脂治疗可改善这种情况下的纤溶功能。因此，我们对21名混合性高脂血症男性患者进行了一项关于吉非贝齐治疗对纤溶功能影响的双盲、安慰剂对照、交叉研究。在静息状态、精神应激期间和静脉阻塞后进行测量。患者的纤溶功能明显紊乱，静息时纤溶酶原激活物抑制剂-1（PAI-1）活性升高（约25 U/mL；参考值，<15 U/mL）。吉非贝齐降低了血浆总胆固醇和极低密度脂蛋白胆固醇以及所有甘油三酯组分，而高密度脂蛋白胆固醇升高（所有P<0.001）。总甘油三酯水平降低了57±4%（从5.3 mmol/L降至2.1 mmol/L）。吉非贝齐治疗未改变空腹血清胰岛素水平。在静息状态和激发试验期间，吉非贝齐治疗均未影响血浆PAI-1活性、组织型纤溶酶原激活物（TPA）活性或抗原水平。D-二聚体、纤溶酶/抗纤溶酶复合物和纤维蛋白原水平也不受吉非贝齐治疗的影响。在安慰剂治疗期间，精神应激可使血浆TPA升高（P=0.0036）并降低PAI-1活性（P=美国代写论文0.0012），但在吉非贝齐治疗期间则无此作用（分别为P=0.28和P=0.17），但通过方差分析对差值（即应激减去静息）进行分析时，治疗效果无差异。静脉阻塞可降低PAI-1活性，而在两种治疗期间TPA和纤溶酶/抗纤溶酶复合物均升高。因此，尽管血浆甘油三酯水平显著降低，但吉非贝齐治疗并未改善混合性高脂血症男性患者的纤溶功能或降低纤维蛋白原水平。纤溶功能改善似乎无法解释吉非贝齐的一级预防作用。
