1、PathophysiologyPathophysiology十年十年三十年三十年四十年四十年 1.201.101.061.021.0060.95510204060801000ChylomicronRemnantsVLDLIDLLDLHDL2HDL3Diameter(nm)Density(g/ml)Chylo-micronsLipoprotein(Sub)ClassesLp(a)高脂血症的分型高脂血症的分型 表型表型 血浆血浆4 TC TG CM VLDL LDL 4 TC TG CM VLDL LDL 备注备注 过夜外观过夜外观 I I 奶油上层奶油上层,下层清下层清 易发胰腺炎易发胰腺炎V
2、V 奶油上层奶油上层 易发胰腺炎易发胰腺炎 下层混浊下层混浊 注注:示浓度升高示浓度升高;示浓度正常示浓度正常;示浓度降低示浓度降低（一）（一）HMG-CoAHMG-CoA还原酶抑制药还原酶抑制药 洛伐他汀；辛伐他汀洛伐他汀；辛伐他汀 普伐他汀；氟伐他汀普伐他汀；氟伐他汀（二）胆汁酸结合树脂（二）胆汁酸结合树脂 考来烯胺，考来替泊考来烯胺，考来替泊（三）（三）ACATACAT抑制药抑制药 甲亚油酰胺甲亚油酰胺（一）贝特类（一）贝特类 吉非贝齐；非诺贝特吉非贝齐；非诺贝特（二）烟酸（二）烟酸 烟酸；阿莫替司烟酸；阿莫替司Treatment of HyperlipidemiaExpert Pane
3、l on Detection,Evaluation,and Treatment of High Blood Cholesterol in Adults.JAMA 2001;285:2486-2497.Alternative:Resin or niacinStatins:Mechanism of ActionLDL receptormediated hepatic uptake of LDL and VLDL remnantsSerum VLDL remnantsSerum LDL-CCholesterol synthesisLDL receptor(BE receptor)synthesisI
4、ntracellular CholesterolApo BApo EApo BSystemic CirculationHepatocyteReduce hepatic cholesterol synthesis,lowering intracellular cholesterol,which stimulates upregulation of LDL receptor and increases the uptake of non-HDL particles from the systemic circulation.LDLSerum IDLVLDLRVLDLPotential Time C
5、ourse of Statin Effects调调血血脂脂改善血改善血管内皮管内皮细胞功细胞功能能减轻减轻炎性炎性反应反应减少减少缺血缺血发作发作稳定稳定斑块斑块减少心减少心血管事血管事件件n调血脂作用调血脂作用n非调脂作用非调脂作用 改善血管内皮；促进血管平滑肌细胞凋亡；改善血管内皮；促进血管平滑肌细胞凋亡；稳定斑块；减轻血管炎性反应；稳定斑块；减轻血管炎性反应；抑制血小板聚集等抑制血小板聚集等n调血脂调血脂n肾病综合征肾病综合征n血管形成术后再狭窄血管形成术后再狭窄n预防心脑血管急性事件预防心脑血管急性事件n器官移植术后的排斥反应和骨质疏松症器官移植术后的排斥反应和骨质疏松症Law MR
6、et al.BMJ.2003;326:1423-1427.Absolute reductions*(mg/dL)and(percentage reductions)Statin10 mg/d20 mg/d40 mg/d80 mg/dAtorvastatin 阿伐他汀阿伐他汀69(37)80(43)91(49)102(55)Fluvastatin氟伐他汀氟伐他汀29(15)39(21)50(27)61(33)Lovastatin洛伐他汀洛伐他汀39(21)54(29)68(37)83(45)Pravastatin普伐他汀普伐他汀37(20)45(24)53(29)62(33)Simvastati
7、n 辛伐他汀辛伐他汀51(27)60(32)69(37)78(42)*Standardized to LDL-C 186 mg/dL(mean concentration in trials)before treatment.Independent of pretreatment LDL-C.Maximum dose of 80 mg/d administered as two 40-mg tablets.Not FDA approved at 80 mg/d.LDL-C Lowering According to Statin andDose:A Meta-analysis of 164 T
8、rialsStatin Adverse EventsnCommon side effectsHeadache 头痛头痛 Myalgia 肌痛肌痛 Fatigue 疲劳疲劳GI intolerance Flu-like symptoms 流感样症状流感样症状nIncrease in liver enzymes（CPK）肌酸磷酸激酶肌酸磷酸激酶Occurs in 0.5 to 2.5%of cases in dose-dependent mannerSerious liver problems are exceedingly rareManage by reducing statin dose o
9、r discontinue until levels return to normalnMyopathy 肌病肌病Occurs in 0.2 to 0.4%of patientsRare cases of rhabdomyolysis 横纹肌溶解横纹肌溶解Reduce bynCautiously using statins in patients with impaired renal functionnUsing the lowest effective dosenCautiously combining statins with fibratesnAvoiding drug interac
10、tionsnCareful monitoring of symptomsPresence of muscle toxicity requires the discontinuation of the statinBile acid binding-resins 胆汁酸结合树脂胆汁酸结合树脂胆胆固固醇醇结合剂结合剂 +胆汁酸胆汁酸 HMG-CoA还原酶还原酶胆固醇胆固醇 7羟化酶羟化酶胆汁酸胆汁酸LDL受受体体肠腔STATINaa及及bb型高脂蛋白血症型高脂蛋白血症,家族性杂合子高脂蛋白血症家族性杂合子高脂蛋白血症特殊臭味特殊臭味,刺激性刺激性;胃肠道反应胃肠道反应避免和某些药物同时服用避免和某
11、些药物同时服用,影响其吸收影响其吸收HMG-CoAHMG-CoA还原酶抑制药还原酶抑制药;叶酸叶酸;铁剂等铁剂等 二二.降低降低TG和和VLDL的药物的药物(一一)贝特类贝特类吉非贝齐吉非贝齐(gimfibrazil(gimfibrazil)非诺贝特非诺贝特(fenofibrate(fenofibrate)降低降低LDL-CLDL-C和和TG;TG;升高升高HDL-CHDL-C 对冠心病防治的价值对冠心病防治的价值-尚无定论尚无定论(二二)烟酸类烟酸类烟酸烟酸(nicotinic acid);(nicotinic acid);阿昔莫司阿昔莫司(acimox(acimox)n降低降低cAMPcA
12、MP水平水平脂肪酶活性降低脂肪酶活性降低 TGTG合成不足合成不足VLDLVLDL减少减少LDLLDL减少减少 HDLHDL分解代谢减少分解代谢减少HDLHDL增高增高n抑制血小板聚集和扩张血管抑制血小板聚集和扩张血管Nicotinic Acid:Mechanism of ActionVLDLVLDLLDL烟酸 niacin临床应用：广谱调血脂药临床应用：广谱调血脂药 bb和和型高脂蛋白血症最好型高脂蛋白血症最好 混合型高脂蛋白血症、高混合型高脂蛋白血症、高TGTG血症、血症、低低HDLHDL血症、高血症、高LpLp（a a）血症）血症Clinical Features of Nicotini
13、c AcidnBest agent to raise HDL-CnReduces coronary events(Coronary Drug Project)nAdverse effectsFlushing,itching,headache(immediate-release,Niaspan)Hepatotoxicity,GI(sustained-release)Activation of peptic ulcerHyperglycemia and reduced insulin sensitivitynContraindicationsActive liver disease or unex
14、plained LFT elevationsPeptic ulcer diseaseTreatment of Mixed HyperlipidemiaExpert Panel on Detection,Evaluation,and Treatment of High Blood Cholesterol in Adults.JAMA 2001;285:2486-2497.第二节第二节 抗氧化剂抗氧化剂防止氧自由基（防止氧自由基（OFROFR）产生和脂蛋白氧化）产生和脂蛋白氧化修饰修饰阻止阻止ASAS发生和发展的重要措施发生和发展的重要措施普罗布考普罗布考 维生素维生素E E，维生素，维生素C C，辅酶，辅酶Q10Q10 第三节第三节 多烯脂肪酸多烯脂肪酸nn-3n-3型多烯脂肪酸型多烯脂肪酸二十碳五烯酸和二十二二十碳五烯酸和二十二碳六烯酸碳六烯酸nn-6n-6型多烯脂肪酸型多烯脂肪酸 亚油酸亚油酸 n低分子量肝素低分子量肝素n天然类肝素天然类肝素n酸性糖酯类酸性糖酯类 第四节第四节 多糖类多糖类n淤阻淤阻n痰阻痰阻n症结症结本标健脾养气健脾养气 滋阴养血滋阴养血 补益肝肾补益肝肾活血化瘀活血化瘀 消食化痰消食化痰 软坚散结软坚散结 通腑化浊通腑化浊
