N,N-二羟乙基甘氨酸-氢氧化钠缓冲液制备的过氧化氢酶复合纳米脂质体的特性分析及过氧化氢酶的药效学初步研究
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摘要
目的:研究过氧化氢酶(catalase,CA)/尿酸酶(uricase,UA)复合纳米脂质体(catalase and uricase nanoliposome,CULP)中过氧化氢酶在大鼠体内的药效学。方法:采用逆向蒸发法制备了CULP,用激光粒度仪测定平均粒径。测定CULP及CA的最适温度和最适pH值。大鼠静脉注射过氧化氢建立高过氧化氢大鼠模型,建模后分别静脉注射CULP和CA,测定不同时间点大鼠血清中过氧化氢的浓度。结果:CULP的平均粒径为1 000 nm。CULP和CA最适温度均为40℃,最适pH值分别为为8.0和7.0。在同一温度和pH条件下,CULP中CA的活性高于游离CA;且CULP在大鼠体内降低过氧化氢浓度的能力高于游离CA。结论:CULP在大鼠体内降低过氧化氢水平的能力优于游离CA,为过氧化氢酶的临床应用提供实验依据。
OBJECTIVE To investigate pharmacodynamics of catalase(CA)in catalase-uricase nanoliposomes(CULP)in rats.METHODS CULP were prepared by reverse-phase evaporation method,and optimal temperature and pH value were detected.Mean particle size was examined by a laser sizer.Rats were intravenously injected hydrogen peroxide to construct high hydrogen peroxide model.Serum hydrogen peroxide concentrations at different times were assayed after intravenous injection of CULP and CA in rats.RESULTS Average diameter was 1 000 nm.Both optimal temperatures for CULP and CA were 40℃,while optimal pH values were 8.0and7.0,respectively.Activity of CULP was higher than that of CA at the same temperature and pH value.CULP was more effective in decreasing hydrogen peroxide in rats.CONCLUSION CULP is significantly superior in decreasing high hydrogen peroxide level in rats to CA,which provides an experimental basis for clinical application of CA.
OBJECTIVE To investigate pharmacodynamics of catalase(CA)in catalase-uricase nanoliposomes(CULP)in rats.METHODS CULP were prepared by reverse-phase evaporation method,and optimal temperature and pH value were detected.Mean particle size was examined by a laser sizer.Rats were intravenously injected hydrogen peroxide to construct high hydrogen peroxide model.Serum hydrogen peroxide concentrations at different times were assayed after intravenous injection of CULP and CA in rats.RESULTS Average diameter was 1 000 nm.Both optimal temperatures for CULP and CA were 40℃,while optimal pH values were 8.0and7.0,respectively.Activity of CULP was higher than that of CA at the same temperature and pH value.CULP was more effective in decreasing hydrogen peroxide in rats.CONCLUSION CULP is significantly superior in decreasing high hydrogen peroxide level in rats to CA,which provides an experimental basis for clinical application of CA.
引文
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[16]Chen Y,Deng YJ,Hao YL,et al.Preparation of cardiomyocyte-targeting liposomes and their targeting ability in vitro[J].Acta Pharmacologica Sinica,2005,40(6):568-572.
[2]Trevisan G,Hoffmeister C,Fortes Rossato M,et al.TRPA1receptor stimulation by hydrogen peroxide is critical to trigger hyperalgesia and inflammation in a model of acute gout[J].Free Radic Biol Med,2014,72C:200-209.
[3]Logan A,Shabalina IG,Prime TA,et al.In vivo levels of mitochondrial hydrogen peroxide increase with age in mtDNA mutator mice[J].Aging Cell,2014,13(4):765-768.
[4]Dai J,Liu M,Ai Q,et al.Involvement of catalase in the protective benefits of metformin in mice with oxidative liver injury[J].Chem Biol Interact,2014,216:34-42.
[5]陈远翔,姜海蓉,彭方毅,等.诊断用苛求芽孢杆菌尿酸酶的剂型与储存方法[J].重庆医科大学学报,2012,37(3):228-231.
[6]Tan QY,Zhang JQ,Wang N,et al.Uricase from Bacillus fastidious loaded in alkaline enzymosomes:Enhanced biochemical and pharmacological characteristics in hypouricemic rats[J].Eur J Pharm Biopharm,2012,82(1):43-48.
[7]Freitas DS,Spencer PJ,Vass o RC,et al.Biochemical and biopharmaceutical properties of PEGylated uricase[J].Inter J Pharm,2010,387(1-2):215-222.
[8]王娜,赵春景,黄开顺,等.产朊假丝酵母尿酸酶脂质纳米粒的制备及其药效学特性分析[J].中国生物制品学杂,2013,26(8):1147-1150.
[9]周雪苹,艾又生.5-氟尿嘧啶热敏长循环脂质体的制备和评价[J].中国医院药学杂志,2013,33(15):1236-1240.
[10]郎杰,朱银硕.大米过氧化氢酶活性的2种测定方法比较[J].中国粮油学报,2014,29(2):89-93.
[11]刁波,唐瑛,王晓昆,等.刺五加多糖对过氧化氢损伤海马神经元中氧自由基的影响[J].中国医院药学杂志,2009,29(1):7-11.
[12]陈思,李辉,马娇颖,等.HPLC法测定猪尿酸酶活性[J].化学与生物工程,2012,29(6):88-91.
[13]Giliano NY,Stepanov SI,Noskin LA,et al.Assessing of the role superoxide,nitric oxide and redox metals in cytotoxic effect of the H2O2and amyloid-beta-protein[J].Patol Fiziol Eksp Ter,2013,(3):42-46.
[14]Wang X,Zhang Y,Li T,et al.Generation 9 polyamidoamine dendrimer encapsulated platinum nanoparticle mimics catalase size,shape,and catalytic activity[J].Langmuir,2013,29(17):5262-5270.
[15]周云莉,杨林,吴建勇,等.尿酸酶复合脂质体中尿酸酶的药动学考察[J].中国医院药学杂志,2014,34(21):1805-1808.
[16]Chen Y,Deng YJ,Hao YL,et al.Preparation of cardiomyocyte-targeting liposomes and their targeting ability in vitro[J].Acta Pharmacologica Sinica,2005,40(6):568-572.