200 Total cholesterol Desirable Borderline: High risk 160 200 230 260 130 LDL cholesterol Desirable Borderline: High risk 100 230 300 HDL cholesterol 100 160 230 Serum lipoprotein(mg/dL) Fiqure 21. 4 Goal lipoprotein levels achieved with dietary or drug therapy for the prevention of coronary heart disease. [Note Lower goals for total and LDL cholesterol are recommended for patients with a history of heart disease
1主要降低TC和LDL的药物 他汀类( Statins):羟甲基 HMG-COA Reductase Inhibitors)-洛代 simvastatin、普伐他汀( pravastatin)、氟伐他汀 (fluvastatin)、 阿伐他汀( (atovastatin) 胆汁酸结合树脂( Bile Acid-Binding Resins, RESINS)-考来替泊 Colestipol),考来烯胺( cholestyramine) 胆固醇吸收抑制药( Cholesterol absorption inhibitors)-依泽替米贝 (ezetimibe) 2主要降低TG和ⅥLDL的药物 烟酸( NICOTINIC ACID,N|Ac|N 苯氧酸类贝特类) FIBRIC AC| D DERIVATIVES(FIBRATES)-氯贝 罪诺贝特 fenofibrate、 贝充 gemfibrozil i)、苯扎贝特( benzafibrate) 贝特 ciprofibrate)
1.主要降低TC和LDL的药物 • 他汀类(Statins)：羟甲基戊二酸单酰辅酶A还原酶抑制剂(HMG-CoA Reductase Inhibitors) – 洛伐他汀(lovastatin)、辛伐他汀 (simvastatin)、普伐他汀(pravastatin)、氟伐他汀(fluvastatin) 、 阿伐他汀(atovastatin) • 胆汁酸结合树脂 (Bile Acid-Binding Resins, RESINS) – 考来替泊 (Colestipol), 考来烯胺 (cholestyramine) • 胆固醇吸收抑制药(Cholesterol absorption inhibitors) –依泽替米贝 (ezetimibe) 2.主要降低TG和VLDL的药物 • 烟酸 (NICOTINIC ACID, NIACIN) • 苯氧酸类(贝特类) FIBRIC ACID DERIVATIVES (FIBRATES) – 氯贝 特(clofibrate)、吉非贝齐(gemfibrozil)、苯扎贝特(benzafibrate)、 非诺贝特(fenofibrate)、环丙贝特(ciprofibrate)
Cholesterol Synthesis Pathway Acetyl-CoA Acetoacetyl-CoA S-COA S-COA HMG:CoA(羟甲基戊二酸甲酰辅酶 S-COA HMG-COA Reductase OH Mevalonate(甲羟戊酸,MVA Dolichol 人人人 oPP Farnesyl-PP Haem Ubiquinone Farnesylated Proteins (人人人), Squalene Lipoprotein Cholesterol Vitamin D Bile Acids Steroid Hormones Istvan E and Deisenhofer J Science 2001: 292: 1160-1164
Cholesterol Synthesis Pathway （羟甲基戊二酸甲酰辅酶A） （甲羟戊酸，MVA）
1.主要降低TC和DL的药物 他汀类 matins BLOOD creased number of LDL receptors omotes uptake of LDL from blood VLDL 2 PLASMA MEMBRANE Low intracellular cholesterol stimulates the synthesis of LDL receptors, VLDL X0000000DNA mRN Cholesterol Ribosome Mevalonic acid Low intracellular cholesterol decreases CoA、:,→2 NADPH+2H the secretion of VLDL. ENDOPLASMIC RETICULUM ← HMG CoA reductase inhibitors 1 ns inhibit HMG CoA reductase ng to a decreased concentration 2 NADP+ lesterol within the cell HMG CoA Acetat igure 21.5 inhibition of HMG CoA reductase by the statin drugs. HMG CoA=3-hydroxy-3-methylglutaryl coenzyme A; LDL=low. density lipoprotein; VLDL very-low-density lipoprotein
他汀类 (Statins ) 1.主要降低TC 和LDL的药物
DIETARY FAT LNVER To endocrine AND CHOLESTERO glands for steroid hormone synthesis Bile salt Biosynthesis Pickup of cholesterol Fecal of fats and cholesterol cholestero Intestine LDL ◎○ LDL receptor Lymph o88 protein Remnant FERIFHERAL Chylomicrons chylomicrons VLDL (Remnants) TISSUES and cholesteric muscles TG ald TC various organs) Capillaries Capillaries Apo B-100 Hydrolysis of chole sterol triacylglycerols TG in capillaries Plasma LCAT ○ Hydrophilic layer Lipoprotein lipase (protein, phospholipids O Triacylglycerols Glycerol Fatty acids B-Oxidation in peripheral tissues Cholesterol Transpon by serum albumin Returned to liver Resynthesis and storag for glucose synthesis mainly in adipose tissue
LPL TG and TC TG TC