丙戊酸和奥卡西平对儿童良性癫痫伴中央颞区棘波氧化应激水平的影响
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摘要
目的探讨丙戊酸和奥卡西平对儿童良性癫痫伴中央颞区棘波(BECT)患儿氧化应激水平的影响。方法选取正常儿童30例作为对照组,新诊断BECT患儿64例作为观察组,并通过随机数字法将64例患儿分成丙戊酸组和奥卡西平组,每组32例,两组患儿分别服用丙戊酸和奥卡西平治疗,分别在药物治疗前、治疗后3月、治疗后6月检测血浆一氧化氮、丙二醛及黄嘌呤氧化酶(XO)水平。结果观察组患儿血浆一氧化氮、丙二醛及XO水平高于对照组患儿(P<0.05)。丙戊酸组患儿治疗前、治疗后3月和6月血浆一氧化氮、丙二醛和XO水平差异无统计学意义(P>0.05)。奥卡西平组患儿治疗后3月和6月血浆一氧化氮、丙二醛和XO水平均显著低于治疗前(P<0.05)。结论 BECT患儿体内氧化应激水平显著升高,丙戊酸对BECT患儿体内氧化应激水平无明显影响,奥卡西平可显著降低BECT患儿体内氧化应激水平,值得在临床上推广。
Objective To explore the effect of valproate and oxcarbazepine on oxidative stress in benign childhood epilepsy with centrotemporal spikes(BECT) children. Methods Thirty healthy children were assigned to the control group, and 64 newly diagnosed BECT children were assigned to the experimental group. Moreover, 64 newly diagnosed BECT children in the experimental group were randomly assigned to the valproate(VPA) group(n=32) and the oxcarbazepine(OXC) group(n=32).Children in the VPA group and OXC group received VPA and OXC treatment, respectively. Nitric oxide(NO),malondialdehyde(MDA) and xanthine oxidase(XO) were detected before and 3 months and 6 months after treatment. Results NO, MDA and XO levels in the experimental group were significantly higher than that in the control group(P<0.05). There were no significant differences in NO, MDA and XO levels among before and 3 months and 6 months after VPA treatment(P>0.05). In the OXC group, NO, MDA and XO levels were significantly higher after 3 months and 6 months than that before treatment(P<0.05). Conclusion Oxidative stress is higher in BECT children. OXC could significantly reduce oxidative stress in BECT children while VPA could not, which is worth popularizing clinically.
Objective To explore the effect of valproate and oxcarbazepine on oxidative stress in benign childhood epilepsy with centrotemporal spikes(BECT) children. Methods Thirty healthy children were assigned to the control group, and 64 newly diagnosed BECT children were assigned to the experimental group. Moreover, 64 newly diagnosed BECT children in the experimental group were randomly assigned to the valproate(VPA) group(n=32) and the oxcarbazepine(OXC) group(n=32).Children in the VPA group and OXC group received VPA and OXC treatment, respectively. Nitric oxide(NO),malondialdehyde(MDA) and xanthine oxidase(XO) were detected before and 3 months and 6 months after treatment. Results NO, MDA and XO levels in the experimental group were significantly higher than that in the control group(P<0.05). There were no significant differences in NO, MDA and XO levels among before and 3 months and 6 months after VPA treatment(P>0.05). In the OXC group, NO, MDA and XO levels were significantly higher after 3 months and 6 months than that before treatment(P<0.05). Conclusion Oxidative stress is higher in BECT children. OXC could significantly reduce oxidative stress in BECT children while VPA could not, which is worth popularizing clinically.
引文
[1]张月华,刘晓燕,杨志仙,等.儿童良性癫痫伴中央颞区棘波变异型的临床和脑电图特点[C]//第三届北京国际癫痫论坛论文集,北京,2009.
[2]Erakovic V,Zupan G,Varljen J,et al.Altered activities of rat brain metabolic enzymes in electroconvulsive Shock-Induced seizures[J].Epilepsia,2010,42(2):181-9.
[3]Rauca C,Zerbe R,Jantze H.Formation of free hydroxyl radicals after pentylenetetrazol-induced seizure and kindling[J].Brain Res,1999,847(2):347-51.
[4]Bruce AJ,Baudry M.Oxygen free radicals in rat limbic structures after kainate-induced seizures[J].Free Radic Biol Med,1995,18(6):993-1002.
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[6]Loiseau P,Beaussart M.The seizures of benign childhood epilepsy with rolandic paroxysmal discharges[J].Epilepsia,1973,14(4):381-9.
[7]Wongekkabut J,Xu Z,Triampo W,et al.Effect of lipid peroxidation on the properties of lipid bilayers:a molecular dynamics study[J].Biophys J,2007,93(12):4225-36.
[8]Stewart AG,Phan LH,Grigoriadis G.Physiological and pathophysiological roles of nitric oxide[J].Microsurgery,2010,15(10):693-702.
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[10]Ribeiro LR,Fighera MR,Oliveira MS,et al.Methylmalonateinduced seizures are attenuated in inducible nitric oxide synthase knockout mice[J].Internation J Development Neuroscien,2009,27(2):157-63.
[11]Rundfeldt C,Koch R,Richter A,et al.Dose-dependent anticonvulsant and proconvulsant effects of nitric oxide synthase inhibitors on seizure threshold in a cortical stimulation model in rats[J].Eur J Pharmacol,1995,274(1/3):73-81.
[12]Peker E,Oktar S,An M,et al.Nitric oxide,lipid peroxidation,and antioxidant enzyme levels in epileptic children using valproic acid[J].Brain Res,2009,1297(2):194-7.
[13]Freire Royes LF,Fighera MR,Furian AF,et al.The role of nitric oxide on the convulsive behavior and oxidative stress induced by methylmalonate:An electroencephalographic and neurochemical study[J].Epilepsy Res,2007,73(3):228-37.
[14]Armstead WM,Mirro R,Leffler CW,et al.Cerebral superoxide anion generation during seizures in newborn pigs[J].J Cereb Blood Flow Metab,1989,9(2):175-9.
[15]Oliver CN,Starke-Reed PE,Stadtman ER,et al.Oxidative damage to brain proteins,loss of glutamine synthetase activity,and production of free radicals during ischemia/reperfusion-induced injury to gerbil brain[J].Proc Natl Acad Sci USA,1990,87(13):5144-7.
[16]Singh R,Pathak DN.Lipid peroxidation and glutathione peroxidase,glutathione reductase,superoxide dismutase,catalase,and glucose-6-phosphate dehydrogenase activities in FeCl3-induced epileptogenic foci in the rat brain[J].Epilepsia,2010,31(1):15-26.
[17]Yüksel A,Cengiz M,Seven M,et al.Changes in the antioxidant system in epileptic children receiving antiepileptic drugs:two-year prospective studies[J].J Child Neurol,2001,16(8):603-9.
[18]Michoulas A,Tong V,Teng XW,et al.Oxidative stress in children receiving valproic acid[J].J Pediatr,2006,149(5):692-6.
[19]Verrotti A,Scardapane A,Franzoni EA,et al.Increased oxidative stress in epileptic children treated with valproic acid[J].Epilepsy Res,2008,78(2/3):171-7.
[20]Yis U,Seckin E,Kurul SH,et al.Effects of epilepsy and valproic acid on oxidant status in children with idiopathic epilepsy[J].Epilepsy Res,2009,84(2/3):232-7.
[21]Michaelis M,Michaelis UR,Fleming I,et al.Valproic acid inhibits angiogenesis in vitro and in vivo[J].Mol Pharmacol,2004,65(3):520-7.
[22]Faradji H,Rousset C,Debilly G,et al.Sleep and epilepsy:a key role for nitric oxide[J].Epilepsia,2010,41(7):794-801.
[23]Karabiber H,Yakinci C,Durmaz Y,et al.Serum nitrite and nitrate levels in epileptic children using valproic acid or carbamazepine[J].Brain Developm,2004,26(1):15-8.
[24]Czuczwar SJ,Tutka P,Klonowski P,et al.N(G)-nitro-L-arginine impairs the anticonvulsive action of ethosuximide against pentylenetetrazol[J].Eur J Pharmacol,1999,366(2/3):137-45.
[25]Nagatomo I,Akasaki Y,Uchida M,et al.Effects of combined administration of zonisamide and valproic acid or phenytoin to nitric oxide production,monoamines and zonisamide concentrations in the brain of seizure-susceptible EL mice[J].Brain Res Bull,2000,53(2):211-8.
[26]Tutka P,Luszczki J,Kleinrok Z,et al.Molsidomine enhances the protective activity of valproate against pentylenetetrazole-induced seizures in mice[J].J Neural Transm,2002,109(4):455-66.
[27]Finkel T,Holbrook NJ.Oxidants,oxidative stress and the biology of ageing[J].Nature,2000,408(689):239-47.
[28]Jeding I,Evans PJ,Akanmu D,et al.Characterization of the potential antioxidant and pro-oxidant actions of some neuroleptic drugs[J].Biochem Pharmacol,1995,49(3):359-65.
[29]Cotariu D,Evans S,Zaidman JL,et al.Early changes in hepatic redox homeostasis following treatment with a single dose of valproic acid[J].Biochem Pharmacol,1990,40(3):589-93.
[30]Chang TK,Abbott FS.Oxidative stress as a mechanism of valproic acid-associated hepatotoxicity[J].Drug Metab Rev,2006,38(4):627-39.
[31]Sobaniec W,Solowiej E,Kulak W,et al.Evaluation of the influence of antiepileptic therapy on antioxidant enzyme activity and lipid peroxidation in erythrocytes of children with epilepsy[J].J Child Neurol,2006,21(7):558-64.
[32]Cengiz M,Yüksel A,Seven M.The effects of carbamazepine and valproic acid on the erythrocyte glutathione,glutathione peroxidase,superoxide dismutase and serum lipid peroxidation in epileptic children[J].Pharmacological Research,2000,11(1):73-82.
[33]陶钧宇,胡华强.丙戊酸钠和奥卡西平对癫患儿认知功能的影响[J].医药导报,2011,30(10):1314-5.
[34]李雪东.丙戊酸与奥卡西平治疗小儿癫痫的效果对比研究[J].中国社区医师,2017,23(15):56-7.
[35]许俊翱.奥卡西平与丙戊酸钠治疗儿童癫痫部分性发作的临床效果比较[J].现代养生,2015,20(12):53-6.
[2]Erakovic V,Zupan G,Varljen J,et al.Altered activities of rat brain metabolic enzymes in electroconvulsive Shock-Induced seizures[J].Epilepsia,2010,42(2):181-9.
[3]Rauca C,Zerbe R,Jantze H.Formation of free hydroxyl radicals after pentylenetetrazol-induced seizure and kindling[J].Brain Res,1999,847(2):347-51.
[4]Bruce AJ,Baudry M.Oxygen free radicals in rat limbic structures after kainate-induced seizures[J].Free Radic Biol Med,1995,18(6):993-1002.
[5]Reinikainen KJ,Ker?nen T,Halonen T,et al.Comparison of oxcarbazepine and carbamazepine:a double-blind study[J].Epilepsy Res,1987,1(5):284-9.
[6]Loiseau P,Beaussart M.The seizures of benign childhood epilepsy with rolandic paroxysmal discharges[J].Epilepsia,1973,14(4):381-9.
[7]Wongekkabut J,Xu Z,Triampo W,et al.Effect of lipid peroxidation on the properties of lipid bilayers:a molecular dynamics study[J].Biophys J,2007,93(12):4225-36.
[8]Stewart AG,Phan LH,Grigoriadis G.Physiological and pathophysiological roles of nitric oxide[J].Microsurgery,2010,15(10):693-702.
[9]Sandirasegarane L,Mikler JR,Tuchek JM,et al.Enhanced forebrain nitric oxide synthase activity in epileptic fowl[J].Brain Res,1996,735(2):311-3.
[10]Ribeiro LR,Fighera MR,Oliveira MS,et al.Methylmalonateinduced seizures are attenuated in inducible nitric oxide synthase knockout mice[J].Internation J Development Neuroscien,2009,27(2):157-63.
[11]Rundfeldt C,Koch R,Richter A,et al.Dose-dependent anticonvulsant and proconvulsant effects of nitric oxide synthase inhibitors on seizure threshold in a cortical stimulation model in rats[J].Eur J Pharmacol,1995,274(1/3):73-81.
[12]Peker E,Oktar S,An M,et al.Nitric oxide,lipid peroxidation,and antioxidant enzyme levels in epileptic children using valproic acid[J].Brain Res,2009,1297(2):194-7.
[13]Freire Royes LF,Fighera MR,Furian AF,et al.The role of nitric oxide on the convulsive behavior and oxidative stress induced by methylmalonate:An electroencephalographic and neurochemical study[J].Epilepsy Res,2007,73(3):228-37.
[14]Armstead WM,Mirro R,Leffler CW,et al.Cerebral superoxide anion generation during seizures in newborn pigs[J].J Cereb Blood Flow Metab,1989,9(2):175-9.
[15]Oliver CN,Starke-Reed PE,Stadtman ER,et al.Oxidative damage to brain proteins,loss of glutamine synthetase activity,and production of free radicals during ischemia/reperfusion-induced injury to gerbil brain[J].Proc Natl Acad Sci USA,1990,87(13):5144-7.
[16]Singh R,Pathak DN.Lipid peroxidation and glutathione peroxidase,glutathione reductase,superoxide dismutase,catalase,and glucose-6-phosphate dehydrogenase activities in FeCl3-induced epileptogenic foci in the rat brain[J].Epilepsia,2010,31(1):15-26.
[17]Yüksel A,Cengiz M,Seven M,et al.Changes in the antioxidant system in epileptic children receiving antiepileptic drugs:two-year prospective studies[J].J Child Neurol,2001,16(8):603-9.
[18]Michoulas A,Tong V,Teng XW,et al.Oxidative stress in children receiving valproic acid[J].J Pediatr,2006,149(5):692-6.
[19]Verrotti A,Scardapane A,Franzoni EA,et al.Increased oxidative stress in epileptic children treated with valproic acid[J].Epilepsy Res,2008,78(2/3):171-7.
[20]Yis U,Seckin E,Kurul SH,et al.Effects of epilepsy and valproic acid on oxidant status in children with idiopathic epilepsy[J].Epilepsy Res,2009,84(2/3):232-7.
[21]Michaelis M,Michaelis UR,Fleming I,et al.Valproic acid inhibits angiogenesis in vitro and in vivo[J].Mol Pharmacol,2004,65(3):520-7.
[22]Faradji H,Rousset C,Debilly G,et al.Sleep and epilepsy:a key role for nitric oxide[J].Epilepsia,2010,41(7):794-801.
[23]Karabiber H,Yakinci C,Durmaz Y,et al.Serum nitrite and nitrate levels in epileptic children using valproic acid or carbamazepine[J].Brain Developm,2004,26(1):15-8.
[24]Czuczwar SJ,Tutka P,Klonowski P,et al.N(G)-nitro-L-arginine impairs the anticonvulsive action of ethosuximide against pentylenetetrazol[J].Eur J Pharmacol,1999,366(2/3):137-45.
[25]Nagatomo I,Akasaki Y,Uchida M,et al.Effects of combined administration of zonisamide and valproic acid or phenytoin to nitric oxide production,monoamines and zonisamide concentrations in the brain of seizure-susceptible EL mice[J].Brain Res Bull,2000,53(2):211-8.
[26]Tutka P,Luszczki J,Kleinrok Z,et al.Molsidomine enhances the protective activity of valproate against pentylenetetrazole-induced seizures in mice[J].J Neural Transm,2002,109(4):455-66.
[27]Finkel T,Holbrook NJ.Oxidants,oxidative stress and the biology of ageing[J].Nature,2000,408(689):239-47.
[28]Jeding I,Evans PJ,Akanmu D,et al.Characterization of the potential antioxidant and pro-oxidant actions of some neuroleptic drugs[J].Biochem Pharmacol,1995,49(3):359-65.
[29]Cotariu D,Evans S,Zaidman JL,et al.Early changes in hepatic redox homeostasis following treatment with a single dose of valproic acid[J].Biochem Pharmacol,1990,40(3):589-93.
[30]Chang TK,Abbott FS.Oxidative stress as a mechanism of valproic acid-associated hepatotoxicity[J].Drug Metab Rev,2006,38(4):627-39.
[31]Sobaniec W,Solowiej E,Kulak W,et al.Evaluation of the influence of antiepileptic therapy on antioxidant enzyme activity and lipid peroxidation in erythrocytes of children with epilepsy[J].J Child Neurol,2006,21(7):558-64.
[32]Cengiz M,Yüksel A,Seven M.The effects of carbamazepine and valproic acid on the erythrocyte glutathione,glutathione peroxidase,superoxide dismutase and serum lipid peroxidation in epileptic children[J].Pharmacological Research,2000,11(1):73-82.
[33]陶钧宇,胡华强.丙戊酸钠和奥卡西平对癫患儿认知功能的影响[J].医药导报,2011,30(10):1314-5.
[34]李雪东.丙戊酸与奥卡西平治疗小儿癫痫的效果对比研究[J].中国社区医师,2017,23(15):56-7.
[35]许俊翱.奥卡西平与丙戊酸钠治疗儿童癫痫部分性发作的临床效果比较[J].现代养生,2015,20(12):53-6.