氧化苦参碱对砷致大鼠脑组织氧化损伤的影响
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摘要
目的探讨氧化苦参碱(oxymatrine,OMT)对砷暴露大鼠脑组织氧化损伤的影响。方法将64只健康成年清洁级雄性Wistar大鼠按体重随机分为4组,分别为正常对照(去离子水)组、亚砷酸钠染毒(5.0 mg/kg)组和低(25 mg/kg)、高剂量(50 mg/kg)氧化苦参碱干预组,每组16只。亚砷酸钠染毒组和各剂量氧化苦参碱干预组采用经口灌胃的方式进行染毒,每天1次,每周6 d,连续染毒16周。适应性喂养1 d后,各剂量氧化苦参碱干预组采用经口灌胃方式进行染毒,每天1次,每周6 d,连续染毒8周;亚砷酸钠染毒组灌胃去离子水。分别于亚砷酸钠和氧化苦参碱染毒结束后,每组选择8只大鼠,检测脑组织总超氧化物歧化酶(total superoxide dismutase,T-SOD)水平、谷胱甘肽过氧化物酶(glutathione peroxidase,GSH-Px)活力和砷、丙二醛(malondialdehyde,MDA)含量。结果在亚砷酸钠染毒及OMT干预结束后,亚砷酸钠染毒组和各剂量OMT干预组大鼠的脑砷含量均高于正常对照组,差异有统计学意义(P<0.05);亚砷酸钠染毒组和各剂量OMT干预组大鼠的脑砷含量间比较,差异均无统计学意义(P>0.05)。在亚砷酸钠染毒及OMT干预结束后,与正常对照组比较,亚砷酸钠染毒组和各剂量OMT干预组大鼠脑组织T-SOD水平、GSH-Px活力均较低,而MDA含量均较高,差异有统计学意义(P<0.05)。在OMT干预结束后,与亚砷酸钠染毒组比较,各剂量OMT干预组大鼠脑组织T-SOD水平、GSH-Px活力均较高,而MDA含量均较低,差异有统计学意义(P<0.05);且随着OMT染毒剂量的升高,亚砷酸钠染毒大鼠脑组织T-SOD水平、GSH-Px活力均呈上升趋势,而MDA含量呈下降趋势。结论 OMT能有效地拮抗砷致大鼠脑组织的氧化损伤作用。
Objective To investigate the antagonistic effect of oxymatrine(OMT) on oxidative damage in brain of rats exposed to arsenic. Methods Sixty-four healthy adult clean grade male Wistar rats were randomly divided into four groups, the normal control group(deionized water), sodium arsenite(5.0 mg/kg) group, and low(25 mg/kg), high-dose(50 mg/kg) oxymatrine intervention groups, 16 in each group. The sodium arsenite exposure group and every oxymatrine intervention group were treated with the agents through gavage, once a day,six days per week,for 16 consecutive weeks. Eight rats in each group were selected for the determination of total superoxide dismutase(T-SOD), glutathione peroxidase(GSH-Px), arsenic and malondialdehyde(MDA) levels in brain tissue after the administration of sodium arsenite and oxymatrine respectively. Results At the end of the sodium arsenite treatment and OMT intervention, the arsenic contents in brain of sodium arsenite group and each dose OMT intervention group were significantly higher compared with the normal control group(P<0.05) and there was no significant difference between sodium arsenite group and OMT intervention groups(P>0.05). After intervention with OMT,compared with the sodium arsenite group, the T-SOD levels and GSH-Px activities in the OMT-treated groups were higher, the MDA contents were lower with significant differences(P<0.05). With the increase of OMT dose, the T-SOD levels and GSH-Px activities in brain tissue of rats exposed to sodium arsenite increased, the MDA contents showed a decreasing trend.Conclusion OMT can effectively antagonize the oxidative damage induced by arsenic in brain tissue of rats
Objective To investigate the antagonistic effect of oxymatrine(OMT) on oxidative damage in brain of rats exposed to arsenic. Methods Sixty-four healthy adult clean grade male Wistar rats were randomly divided into four groups, the normal control group(deionized water), sodium arsenite(5.0 mg/kg) group, and low(25 mg/kg), high-dose(50 mg/kg) oxymatrine intervention groups, 16 in each group. The sodium arsenite exposure group and every oxymatrine intervention group were treated with the agents through gavage, once a day,six days per week,for 16 consecutive weeks. Eight rats in each group were selected for the determination of total superoxide dismutase(T-SOD), glutathione peroxidase(GSH-Px), arsenic and malondialdehyde(MDA) levels in brain tissue after the administration of sodium arsenite and oxymatrine respectively. Results At the end of the sodium arsenite treatment and OMT intervention, the arsenic contents in brain of sodium arsenite group and each dose OMT intervention group were significantly higher compared with the normal control group(P<0.05) and there was no significant difference between sodium arsenite group and OMT intervention groups(P>0.05). After intervention with OMT,compared with the sodium arsenite group, the T-SOD levels and GSH-Px activities in the OMT-treated groups were higher, the MDA contents were lower with significant differences(P<0.05). With the increase of OMT dose, the T-SOD levels and GSH-Px activities in brain tissue of rats exposed to sodium arsenite increased, the MDA contents showed a decreasing trend.Conclusion OMT can effectively antagonize the oxidative damage induced by arsenic in brain tissue of rats
引文
[1]于云江,王菲菲,房吉敦,等.环境砷对人体健康影响的研究进展[J].环境与健康杂志,2007,24(3):181-183.
[2]赵朔,李冰.砷的神经系统损伤作用研究进展[J].中国地方病防治杂志,2014,29(2):98-101.
[3]朱筑霞,吴泽江,胡晓霞,等.胚胎期和生长期大鼠砷暴露对仔鼠体重和脑神经递质的影响[J].环境与健康杂志,2010,27(9):820-822.
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[7]Wu XL,Zeng W Z,Jiang MD,et al.Effect of oxymatrine on the TGF beta-Smad signaling pathway in rats with CCl4-induced hepatic fibrosis[J].World J Gastroenterol,2008,13:2100-2105.
[8]Ito H,Tamura M,Matsui H,et al.Reactive oxygen species involved cancer cellular specific 5-aminolevulinic acid uptake in gastric epithelial cells[J].J Clin Biochem Nutr,2014,2:81-85.
[9]石磊,史丽娟.中药单体——氧化苦参碱药理作用研究新进展[J].山西医药杂志,2015,44(2):123-126.
[10]姚茂林,张爱华,于春,等.高砷煤烘玉米粉致大鼠砷中毒模型的建立[J].中华预防医学杂志,2013,47(9):799-805.
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[12]程钢,秦媛媛,程迪,等.氧化苦参碱对大鼠局灶性脑缺血损伤的保护作用及其抑制凋亡的作用机制[J].中国药理学通报,2013,29(3):387-392.
[13]沈雪,薛启祥,谢汝佳,等.氧化苦参碱对亚砷酸钠致人肝细胞损伤的拮抗作用[J].环境与健康杂志,2015,32(3):207-210.
[14]卢继承.大脑功能对葡萄糖依赖的生物化学基础[J].生物学教学,2004(3):50-51.
[15]Cheng CY,Tsung JH,Chin CW,et al.Inorganic arsenic causes cell apoptosis in mouse cerebrum through an oxidative stress-regulated signaling pathway[J].Arch Toxicol,2011,6:565-575.
[16]Chattopadhyay S,Bhaumik S,Purkayastha M,et al.Apoptosis and necrosis in developing brain cells due to arsenic toxicity and protection with antioxidants[J].Toxicol Lett,2002,1:65-76.
[17]孙贵范.深入研究慢性砷中毒的分子作用机制[J].中国地方病学杂志,2004,23(1):1-2.
[18]李少康,徐力,许力,等.氧化苦参碱对心衰大鼠血流动力学影响的研究[J].实用中医内科杂志,2010,24(2):39-40.
[19]Barnes PJ,Karin M.Nuclear factor-kappa B:a pivotal transcription factor in chronic inflammatory diseases[J].N Engl J Med,1997,15:1066-1071.
[20]胡海波.氧化苦参碱对心血管疾病的药理作用及其机制研究进展[J].中国药业,2012,21(13):110.
[21]韩延忠,周永峰,桑秀秀,等.氧化苦参碱对H2O2诱导L02细胞损伤的抑制作用及其机制的研究[J].中国中药志,2016,41(7):1302-1307.
[2]赵朔,李冰.砷的神经系统损伤作用研究进展[J].中国地方病防治杂志,2014,29(2):98-101.
[3]朱筑霞,吴泽江,胡晓霞,等.胚胎期和生长期大鼠砷暴露对仔鼠体重和脑神经递质的影响[J].环境与健康杂志,2010,27(9):820-822.
[4]Lynn S,Gurr JR,Lai HT,et al.NADH oxidase activation is in volved in arsenite-induced oxidative DNA damage in human vascular smooth muscle cells[J].Circ Res,2000,5:514-519.
[5]Kannan GM,Tripathi N,Dube SN,et al.Toxic effects of arsenic(Ⅲ)on some hematopoietic and central nervous system variables in rats and guinea pigs[J].Toxicol Clin Toxicol,2001,7:675-682.
[6]孙贵范,王惠惠,徐苑苑,等.亚砷酸钠致Chang liver细胞氧化应激作用的研究[J].环境与健康杂志,2008,25(7):568-570.
[7]Wu XL,Zeng W Z,Jiang MD,et al.Effect of oxymatrine on the TGF beta-Smad signaling pathway in rats with CCl4-induced hepatic fibrosis[J].World J Gastroenterol,2008,13:2100-2105.
[8]Ito H,Tamura M,Matsui H,et al.Reactive oxygen species involved cancer cellular specific 5-aminolevulinic acid uptake in gastric epithelial cells[J].J Clin Biochem Nutr,2014,2:81-85.
[9]石磊,史丽娟.中药单体——氧化苦参碱药理作用研究新进展[J].山西医药杂志,2015,44(2):123-126.
[10]姚茂林,张爱华,于春,等.高砷煤烘玉米粉致大鼠砷中毒模型的建立[J].中华预防医学杂志,2013,47(9):799-805.
[11]李闯,王震.氧化苦参碱对大鼠心肌缺血的保护作用[J].中国老年学杂志,2014,24(10):7024-7026.
[12]程钢,秦媛媛,程迪,等.氧化苦参碱对大鼠局灶性脑缺血损伤的保护作用及其抑制凋亡的作用机制[J].中国药理学通报,2013,29(3):387-392.
[13]沈雪,薛启祥,谢汝佳,等.氧化苦参碱对亚砷酸钠致人肝细胞损伤的拮抗作用[J].环境与健康杂志,2015,32(3):207-210.
[14]卢继承.大脑功能对葡萄糖依赖的生物化学基础[J].生物学教学,2004(3):50-51.
[15]Cheng CY,Tsung JH,Chin CW,et al.Inorganic arsenic causes cell apoptosis in mouse cerebrum through an oxidative stress-regulated signaling pathway[J].Arch Toxicol,2011,6:565-575.
[16]Chattopadhyay S,Bhaumik S,Purkayastha M,et al.Apoptosis and necrosis in developing brain cells due to arsenic toxicity and protection with antioxidants[J].Toxicol Lett,2002,1:65-76.
[17]孙贵范.深入研究慢性砷中毒的分子作用机制[J].中国地方病学杂志,2004,23(1):1-2.
[18]李少康,徐力,许力,等.氧化苦参碱对心衰大鼠血流动力学影响的研究[J].实用中医内科杂志,2010,24(2):39-40.
[19]Barnes PJ,Karin M.Nuclear factor-kappa B:a pivotal transcription factor in chronic inflammatory diseases[J].N Engl J Med,1997,15:1066-1071.
[20]胡海波.氧化苦参碱对心血管疾病的药理作用及其机制研究进展[J].中国药业,2012,21(13):110.
[21]韩延忠,周永峰,桑秀秀,等.氧化苦参碱对H2O2诱导L02细胞损伤的抑制作用及其机制的研究[J].中国中药志,2016,41(7):1302-1307.