Gmiński J, Wojakowski W
Katedry i Kliniki Chorób Wewnetrznych Slaskiej Akademii Medycznej w Katowicach.
Przegl Lek. 1997;54(11):782-7.
Statins are most potent lipid-lowering drugs. The mechanisms of their action is specific inhibition of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) activity. HMG-CoA reductase catalyses the reduction of HMG-CoA o mevalonate and is rate-limiting step in cholesterol biosynthesis pathway. Mevalonate is considered to be not only an important intermediate of cholesterol synthesis, but also the source of isoprenoids which play important role in DNA replication and cell growth. It was shown that statins inhibit the proliferation and migration of vascular smooth muscle cell--key events in atherogenesis. HMG-CoA reductase inhibitors lower the reactivity of arterial wall to vasoconstrictor agents, decrease the concentration of lipoprotein [a]--an independent risk factor of atherosclerosis, inhibit the generation of free radicals and lipid peroxidation, decrease the number of macrophages in atherosclerotic lesion and finally, equilibrate the clotting-fibrynolysis processes of attennuating platelets function, reducing the tissue factor synthesis and decreasing the concentration of plasminogen activator inhibitors. Statins are presently considered by NCEP to be the drugs of first choice for treatment of hypercholesterolemia.
他汀类药物是最有效的降脂药物。其作用机制是特异性抑制3-羟基-3-甲基戊二酰辅酶A（HMG-CoA）活性。HMG-CoA还原酶催化HMG-CoA还原为甲羟戊酸，这是胆固醇生物合成途径中的限速步骤。甲羟戊酸不仅被认为是胆固醇合成的重要中间体，也是类异戊二烯的来源，类异戊二烯在DNA复制和细胞生长中起重要作用。研究表明，他汀类药物可抑制血管平滑肌细胞的增殖和迁移，而这是动脉粥样硬化形成过程中的关键事件。HMG-CoA还原酶抑制剂可降低动脉壁对血管收缩剂的反应性，降低脂蛋白[a]的浓度（脂蛋白[a]是动脉粥样硬化的独立危险因素），抑制自由基的产生和脂质过氧化，减少动脉粥样硬化病变中的巨噬细胞数量，最终平衡凝血-纤溶过程，减弱血小板功能，减少组织因子合成，降低纤溶酶原激活物抑制剂的浓度。目前，美国国家胆固醇教育计划（NCEP）认为他汀类药物是治疗高胆固醇血症的首选药物。
