阿托伐他汀对老年缺血性脑卒中患者氧化应激和脂质过氧化影响的研究
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摘要
目的通过检测急性缺血性脑卒中患者使用阿托伐他汀治疗前后外周血中氧化应激和脂质过氧化指标8-iso-PGF2α和ox-LDL的水平,并结合临床参数探讨阿托伐他汀在老年急性缺血性脑卒中患者的治疗过程中的抗氧化应激作用,以期为老年急性缺血性脑卒中患者使用阿托伐他汀抗氧化治疗提供有价值的临床依据。
     方法收集2009年10月至2010年7月入住安徽省立医院神经内科的年龄在60岁以上的脑梗塞急性期(经CT或/和MRI证实)患者,测定其血压、身高、体重,计算体重指数等;采用美国国立卫生研究院卒中量表(NIHSS)的评分标准对所有患者进行神经功能缺损的评估,纳入中度神经功能缺损的患者共57例,其中试验组30例,接受阿托伐他汀治疗,对照组27例,未予阿托伐他汀(或其他他汀类药物)治疗。所有患者均于入院时及治疗10-14天后清晨空腹抽取外周静脉血2ml,1h内离心分离血浆。采用ELISA(酶标记免疫吸附测定,Enzyme linked immunosorbent assay)方法检测血浆中8-iso-PGF2α和ox-LDL的水平,并进行比对和统计学分析。
     结果入院治疗10-14天后试验组8-iso-PGF2α和ox-LDL水平较入院时无明显升高,差异无统计学意义,而对照组8-iso-PGF2α和ox-LDL水平较入院时明显升高,差异有统计学意义(p<0.05)。治疗10~14天后试验组与对照组患者血脂各项水平较入院时差异无明显统计学意义(p>0.05)。治疗10~14天后对所有患者再次进行神经功能评估进行疗效评定,结果显示,试验组治疗有效率较对照组高,但两者差异无统计学意义(p>0.05)。
     结论阿托伐他汀对缺血性脑卒中患者具有调脂作用以外的抗氧化应激和抗脂质过氧化作用。可能对改善老年急性缺血性脑卒中患者临床预后起到积极的作用。
Objective To detect the change of plasmic 8 Isoprostan Prostaglandin F2alpha (8-iso-PGF2α) and Oxidized Low Density Lipoprotein(ox-LDL) in the elderly patients with acute cerebral infarction by atorvastatin. To Explain the affect by atorvastatin about Oxidative stress and Lipid peroxidation in Senile Ischemic stroke ,and provide Antioxidant treatment of acute cerebral infarction clinical basis by atorvastatin.
     Methods Randomly selected 57 cases acute cerebral infarction patients over the age of 60 years,admitted to Neurology of Anhui Provincial Hospital from October in 2009 to July in 2010(Confirmed by CT and MRI),30 cases were treated by atorvastatin, other 27cases were in control group .All blood samples anticoagulated were dealed with centrifugation.All the blood samples were analyzed by enzyme linked immunosorbent assay (ELISA )to detect 8-iso-PGF2αand ox-LDL at admission and after 10~14 days later . They were made comparison and statistical analysis.
     Results After treated 10~14 days later the test group 8-iso-PGF2αand ox-LDL were not change more .but the control group were changed obviously Their difference have statistically significant(P<0.05). After treated 10~14 days the level of the lipids between the test group and the control group have no statistically significant. After treated 10~14 days ,do neurological for all patients for efficacy evaluation,the result display that the test group’s efficient is higher than the control group’s.but have no statistically significant.
     Conclusions Atorvastatin have affects in Anti-Oxidative stress and Anti-Lipid peroxidation outside the Lipid Metabolism. Maybe can improve positive affect in eldly acute cerebral infarction for clinical Prognosis.
引文
1. Dahl A, Lund C, Russell D. Atherosclerosis and cerebral infarction[J]. Tidsskr Nor Laegeforen. 2007 ,127(7):892-96.
    2.王爱华,孙华,孙钦建,等.血浆尿酸水平对急性卒中后病人远期预后的影响[J].中华神经医学杂志, 2007 , 6( 6) : 557- 60.
    3. Zhang DW, Zhang L, et al. Protective effect of fosinopril sodium pretreatment combined with ischemic postconditioning on rat heart underwent myocardial ischemia/reperfusion injury[J]. Zhonghua Xin Xue Guan Bing Za Zhi, 2010 Jul,38(7):633-7.
    4. Honda HM, Korge P, Weiss JN. Mitochondria and ischemia/reperfusion injury[J]. Ann NY Acad Sci, 2005, 1047:248-58.
    5. Rosenberg GA. Ischemic brain edema[J]. Prog Cardiovasc Dis, 1999, 42(3):209-16.
    6.王拥军.脑侧枝循环及氧化应激对其影响[J].中国卒中杂志,2008,3(3):198-201.
    7. Kelly PJ,Morrow JD,Ning M,et al.Oxidative Stress and Matrix Metalloproteinase-9 in Acute Ischemic Stroke:Biomarker Evaluation for Antioxidant Therapies in Stroke(BEAT-Stroke)Study[J] Stroke 2008,39(1):100-4.
    8. Cabral PD,Silva GB,et al.8-iso-prostaglandin-F2αstimulates chloride transport in thick ascending limbs: role of cAMP and protein kinase A[J].Am J Physiol Renal Physiol. 2010 Dec;299(6):F1396-400.
    9. Morrow JD. Quantification of isoprostanes as indices of oxidant stress and the risk of atherosclerosis in humans[J]. Arterioscler Thromb Vasc Biol, 2005,25(2):279-86.
    10.郭乐琴,初桂兰.在缺血缺氧性脑病中氧化应激时异前列烷F2a-Ⅲ的作用[J].国际儿科学杂志, 2006,33(4):227-229.
    11. Schwedhelm E, Bartling A, Lenzen H, et al. Urinary 8-iso-prostaglandin F2alpha as a risk marker in patients with coronary heart disease: a matched case-control study[J]. Circulation. 2004,109(7):843-848.
    12. Vassalle C, Botto N, Andreassi MG, et al. Evidence for enhanced 8-isoprostaneplasma levels, as index of oxidative stress in vivo, in patients with coronary artery disease[J]. Coronary Artery Dis. 2003,14(3):213-218.
    13. Davi G, Falco A, Patrono C.Determinants of F2-isoprostane biosynthesis and inhibition in man[J]. Chem Phys Lipids.2004,128(1-2):149-163
    14. Back SA,Ino NL,Mallinson RA,et al.Selective vulneralbility of pretern white matter to oxidative damage defined by F2-isoprostanes. Ann Neurol. .2005.58(1):108-200.
    15. Akishima Y, Helderman F, Ishikawa Y, et al.Role of macrophage and smooth muscle cell apoptosis in association with oxidized low-density lipoprotein in the atheroselerotic development [J].Mod Pathol,2005,18:365-373.
    16. Bi-lian Yu, Shui-ping Zhao, Xian-sheng Huang. Oxidized low-density lipoprotein: A double-edgedsword on atherosclerosis. Medical Hypotheses 2007. 69, 553–556
    17.蔡志友,晏勇.氧化型低密度脂蛋白致动脉粥样硬化的机制[J].中国卒中杂志. 2008,3(3):187-19.
    18. Gomez M,Valle V, et al. Oxidized LDL,lipoprotein (a) and other emergent risk factors in acute myocardial infarction (FORTIAM study)[J].Rev Esp Cardiol.2009 Apr;62(4):373-82.
    19. Kaneyuki U, Ueda S,Yamagishi S, et al. Pitavastatin inhibits lysophosphatidic acid-induced proliferation and monocyte chemoattractant protein-1expression in aortic smooth muscle cell bysuppressing mediate reactiveoxygen species gnenration[J].Vascul Harmacol,2007,46:286-292.
    20.刘兆阳,丁琪.老年人血脂紊乱、氧化应激与急性脑梗死关系的研究.中国临床保健杂志,2009,12(2):138-140.
    21. Napoli PD, TaccardiAA, OliverM. Statins and stroke: evidence for cholesterol-independent effects[J]. EuropeanHeart J, 2002,23(24): 1908-1921.
    22. Palinski W,Napoli C.Unraveling pleiotropic effects of statins on plaque rupture[ J]. Arterioscler Thromb Vasc Bio,l 2002, 22(11): 1745-1750.
    23.颜建云,黄东轩,陆立鹤,等.辛伐他汀对局部脑缺血大鼠线粒体的抗氧化效应[J].中国临床康复, 2006,10:82-84.
    24.刘勇,唐亚梅,方云祥等. L-NAME对SIM治疗脑缺血/再灌注损伤保护作用的影响[J].中国医师杂志, 2004, 6(2):147-149.
    25. Vasil’eva LV,Lakhin DI.Effect of atorvastatin (liptonorm) on indicators of the lipid spectrum of blood in patients with the metabolic syndrome[J]. Adv Gerontol.2010; 23(2):281-4.
    26. Hoda MN,Singh I,et al.Reduction of lipoxidative load by secretory phospholipase A2 inhibition protects against neurovascular injury following experimental stroke in rat[J].J Neuroinflammation.2009 Aug 13;6:21.
    27. Bonomini F, Tengattini S, Fabiano A, et al. Atherosclerosis and oxidative stress. Histol Histopathol [J]. 2008 ,23(3):381-90.
    28. Sen CK, Packer L. Antioxidant and redox regulation of gene transcription[J]. FASEB J, 1996, 10(7):709-20.
    29. Candelario-Jalil E. Injury and repair mechanisms in isehemic stroke: considerations for the development of novel neumtherapeutics[J]. Curt Opin lnvestig Drugs, 2009, 10(7):644-54.
    30. Duru FI, Olabiyi O, et al. Brief ischaemia reduces testicular lipid peroxidation following subsequent ischaemia: an evidence for ischaemic preconditionning[J].Nig Q J Hosp Med.2008 Jul-Sep;18(3):149-52.
    31.万继峰,徐云燕,郝丽梅,等.脑血管病与血脂关系临床分析[J].中国煤炭工业医学杂志, 2008,11(6):843-844.
    32. Navab M, Imes SS, Hama SY, et al. Monocytetransmigration induced by modification of low density lipoprotein in cocultures of human aortic wall cells is due to induction of monocyte chemotactic protein 1 synthesis and is abolished by high density lipoprotein[J]. J Clin Invest, 1991, 88:2039-46.
    33. Honda HM, Korge P, Weiss JN. Mitochondria and ischemia/reperfusion injury[J]. Ann NY Acad Sci,2005,1047:248-258.
    34.陈红艳,黄正明,等.金丝桃苷对大鼠脑缺血再灌注氧化应激损伤的影响[J].解放军药学学报, 2007,23:88-91.
    35. Oltvai ZN, Milliman CL, Korsmeyer SJ. Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death[J]. Cell, 1993,74:609-19.
    36. Morrow JD , Harris TM , Robert s II LJ. Noncy clooxygenase oxidative for mation of a series of novel prostaglandins : Analytical ramification for measurement of eicosanoids [J] . Anal Biochem ,1990,184:1-10.
    37. Anctil M, Poulain I, Pelletier C. Nitric oxide modulates peristaltic muscle activity associated with fluid circulation in the sea pansy Renilla koellikeri[J]. J Exp Biol, 2005, 208 (10) : 2005-17.
    38. Keller JN, Kindy MS, Holtsberg FW, et al. Mitochondrial manganese superoxide dismutase prevents neural apoptosis and reduces ischemic brain injury: supp ression of peroxynitrite production, lipid peroxidation, and mitochondrial dysfunction[J]. J Neurosci, 1998,18 (2) : 687-97.
    39. Gaur V,Aggarwal A,et al.Protective effect of naringin against ischemic reperfusion cerebral injury possible neurobehavioral biochemical and cellular alterations in rat brain[J].Eur J Pharmacol. 2009 Aug 15;616(1-3):147-54.
    40. Xin Hou, L Jackson Roberts II, Fernand Gobeil Jr, et al. Isomer-specific contractile-effects of synthetic F2-isoprostanes on retinal and cerebral microvasculature [J]. Free Radic Biol Med, 2004,36(2):163-172.
    41. Minuz P, Fava C, Lechi A.lipid peroxidation,isoprostanes and vascular damage [J].Pharmacol Rep.2006,58 Suppl:57-68.
    42. Davi G, Guagnano MT, Ciabattoni G, et al. Platelet activation in obese Women: role of inflammation and oxidant stress[J]. JAMA. 2002,288(16):2008-2014.
    43. Tang M, Cyrus T, Yao Y, et al. Involvement of thromboxane receptor in the proatherogenic effect of isoprostane F2α-III: evidence from apolipoprotein E- and LDL.receptor-deficient mice[J]. Circulation, 2005,112(18):2867-2874.
    44. Feng-Shiun Shie, M Diana Neely, Izumi Maezawa, et al. Oxidized Low-Density Lipoprotein is Present in Astrocytes Surrounding Cerebral Infarcts and StimulatesAstrocyte Interleukin-6 Secretion[J]. American Journal of patbology. 2004,164(4): 1173-1181.
    45. Collot-Teixeira S, Martin J, Mcdermott-Roe C, et al. CD36 and macrophages in atherosclerosis [J]. Cardiovasc Res, 2007,75(3):468-477.
    46. Cojocaru IM, Cojocaru M, Burcin C. IgG-autoantibodies against oxidized low-density lipoprotein in ischemic stroke onset[J]. Rom J Intern Med. 2006,44(2):165-170.
    47. Hong H, Zeng JS, Kreulen DL, et al. atorvastat in protects against cerebral infarction via inhibiting NADPH oxidase-derived superoxide in ischemic stroke[J]. Am J Physiol Heart Circ Physiol, 2006,291:2210-2215.
    48. Nagotani S, Hayashi T, Sato K, et al. Reduction of cerebral infarction in stroke-prone spontaneously hypertensive rats by statins associated with amelioration of oxidative stress[J]. Stroke,2005,36:670-672.
    1.乔木,王文.他汀类药物非降脂作用机制[J].河北医药,2001,23(11):862.
    2. Squizzato A, Dentali F, Romualdi E, et al. Statins and secondary prevention of ischemic and hemorrhagic stroke[J]. Stroke, 2008,39(7):113-115.
    3. Corvol JC, Bouzamondo A, SirolM, et al. Differential effects of lipid-lowering therapies on stroke prevention: ameta-analysis of randomized trials[J]. Arch InternMed, 2003,163(6):669~676.
    4. Law MR,Wald NJ,Monis JK, et a.l Value of low does combination treatmentwith blood pressure lowering drugs: analysis of 354 randomised trials[J]. BMJ, 2003,326(7404):1427.
    5. Amarenco P. Hypecholesterolemia, lipid-lowering agents and the risk for brain infarction[J]. Neurology, 2001,57(5 Suppl 2):S35~44.
    6. Nakaya N, Kita T, Mabuchi H, et al. Large-scale cohort study on the relationship between serum lipid concentrations and risk of cerebrovascular disease under low-dose simvastatin in Japanese patients with hypercholesterolemia sub-analysis of the Japan lipid intervention trial (J-LIT)[J]. Circ J, 2005,69;1016 -1021.
    7. Shook SJ, Gupta R, Vora NA, et al. Statin use is independently associated with smaller infarct volume in nonlacunar MCA territory stroke[J]. J Neuroimaging, 2006,16;341-346.
    8. The SPARCL Investigatiors. Design and baseline characteristics of the stroke prevention by aggressive reduction in cholesterol levels (SPARCL)[J]. Cerebrovasc Dis,2003,16:389-395.
    9. The Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) Investigators. High-dose atorvastatin after stroke or transient ischemic attack[J]. N Engl J Med, 2006,355:549-559,613-615.
    10. Guyton JR. Benefit versus risk in statin treatment[J]. Am J Cardio,2006,97(8A):95~97.
    11. OK' eefe JH Jr, Cordain L,Harris WH, et al. Optimal low-density lipo-protein is 50 to 70mg/d:l lower is better and physiologically normal[J]. J Am CollCardio, 2004,43(11):2142~2146.
    12. Bonetti PO, Lerman LO, NaPoli C, et al. Statin effects beyond lipid lowing are they elinically relevant?[J]. European Heart Journal, 2003;24:225~248.
    13.袁彬.他汀类药物对急性脑梗死患者CRP、TNF-α和血脂的影响[J].中国临床保健杂志, 2008,11(3):298-299.
    14.王会梅.阿托伐他汀对脑梗死患者血脂及高敏C反应蛋白的影响[J].山东医药,2006,46(8):33.
    15. Shabanzadeh AP, Shuaib A, Wang CX. Simvastatin reduced ischemic brain injury and perfusion deficits in an embolic model of stroke[J]. Brain Res, 2005,1042:1-5.
    16. Samdani AF, Dawson TM, Dawson VL. Nitric oxide synthase in models of focal ischemia. [J]. Stroke, 1997,28:1283-1288.
    17. SironiL, CiminoM, GuerriniU, et al. Treatmentwith statins after induction of focal ischemia in rats reduces the extent of brain damage[J]. ArteriosclerThromb Vasc Bio, 2003,23:322-327.
    18. Kawashima S, Yamashita T, Miwa Y, et al. HMG-CoA reductase inhibitor has protective effects against stroke events in stroke-prone spontaneously hypertensive rats[J]. Stroke, 2003, 34:157-163.
    19.余昌胤,袁胜山,张骏.辛伐他汀对大鼠脑缺血再灌注后脑组织NOS表达的影响[J].贵州医药, 2006,30:1069-1071.
    20. Endres M, Laufs U. Effects of statins on endothelium and signaling mechanisms[J]. Stroke, 2004,35:2708-2711.
    21. Dimmeler S, Aicher A, Vasa M, et al. HMG-CoA reductase inhibitors (statins) increase endothelial progenitor cells via the PI 3-kinase/Aktpathway[J]. JClin Invest, 2001,108: 391-397.
    22. Zhang ZG, ZhangL, JiangQ, et al. Bonemarrow-derived endothe-lialprogenitorcellsparticipate in cerebralneovascularization after focal cerebral ischemia in the adultmouse[J]. CircRes, 2002,90:284-288.
    23. Arenillas JF, Sobrino T, Castillo J, et al. The role of angiogenesis in damage and recovery from ischemic stroke[J]. Curr Treat Options CardiovascMed, 2007,9:205 -212.
    24. Chen J, Zhang ZG, Li Y, et al. Statins induce angiogenesis, neuro-genesis, and synaptogenesis after stroke[J]. Ann Neuro,2003,53:743-751.
    25. Hong H, Zeng JS, Kreulen DL, et al. atorvastat in protects against cerebral infarction via inhibiting NADPH oxidase-derived superoxide in ischemic stroke[J]. Am J Physiol Heart Circ Physiol, 2006,291:2210-2215.
    26. Wang E, Casciano CN, Clementr P, et al. HMG-CoA redctase in-hibitors(statins) Characterized asdirect inhibtors of P-glycoprotein[J]. Pharm Res, 2001,18:800.
    27. Laufsu, Gertz K, Huang P, et al. Atorvastatin upregulutes type III nitric oxide synthase in thrombocytes, decreases platelet activation, and protects from cerebral ishemia in normocholester-olemicmice[J]. Stroke, 2000,31:2442.
    28.颜建云,黄东轩,陆立鹤,等.辛伐他汀对局部脑缺血大鼠线粒体的抗氧化效应[J].中国临床康复, 2006,10:82-84.
    29. Nagotani S, Hayashi T, Sato K, et al. Reduction of cerebral infarction in stroke-prone spontaneously hypertensive rats by statins associated with amelioration of oxidative stress[J] .Stroke,2005,36:670-672.
    30. Laufs U, Gertz K, Huang P, et al. Atorvastatin upregulates type III nitric oxide synthase in thrombocytes, decreases platelet activation, and protects from cerebral ischemia in normocholesterolemic mice[J]. Stroke, 2000,31:2442-2449.
    31. Bea F, Blessing E, Shelley MI, et al. Simvastatin inhibits expression of tissue factor in advanced atherosclerotic lesionsofapolipoprotein E deficientmice independently of lipid lowering: potential role of simvastatin-mediated inhibition of Egr-1 expression and activation[J]. Atherosclerosis, 2003,167:187-194.
    32. Baetta R, Camera M, Comparato C, et al. Fluvastatin reduces tissue factorexpressionandmacrophage accumulation in carotid lesions of cholesterol-fed rabbits in the absence of lipid lowering[J]. ArteriosclerThromb Vasc Bio, 2002,22:692-698.
    33. BourcierT, Libby P. HMG CoA reductase inhibitors reduce plasminogen activator inhibitor-1 expression by human vascular smooth muscle and endothelial cells[J]. ArteriosclerThrombVasc Bio, 2000,20:556-562
    34. Zhang L, Zhang ZG, Ding GL, et al. Multitargeted effects of statin-enhanced thrombloytic therapy for stroke with recombinant human tissue-type plasminogen activator in the rat[J]. Circulation, 2005,112:3486-3494.
    35. Cook NR, Cohen J, Hekbert PR, et al. Implicationsofsmall reductions in diastolic blood pressure for primary prevention[J]. Arch Intern Med, 1995,155:701-709.
    36. Amareneo P, Lavallee P, Touboul PJ. Statins and stroke Prevention[J]. Cerebrovase Dis, 2004:17(11):81-82.

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