抑眩宁颗粒对小鼠和大鼠缺血性眩晕的治疗作用及其机制
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摘要
目的:探讨抑眩宁颗粒对缺血性眩晕小鼠和大鼠的治疗作用,阐述其对小鼠和大鼠脑组织炎症损伤及氧化应激的影响。方法:分别采用机械眩晕和结扎双侧颈总动脉(CCA)的方法建立眩晕小鼠和大鼠模型。选择小鼠和大鼠各60只,随机分为正常对照组、模型组、低剂量抑眩宁颗粒组(2.25g·kg~(-1)/1.50g·kg~(-1))、中剂量抑眩宁颗粒组(4.50g·kg~(-1)/3.00g·kg~(-1))、高剂量抑眩宁颗粒组(9.00g·kg~(-1)/6.00g·kg~(-1))和阳性对照组(1.50g·kg~(-1)/1.00mg·kg~(-1)盐酸氟桂利嗪胶囊),每组10只。正常对照组和模型组小鼠和大鼠灌胃给予10mL·kg~(-1)生理盐水,其余各组小鼠和大鼠给予10mL·kg~(-1)相应药物,每天1次,连续给药7d。分别测定各组小鼠和大鼠跳台逃避时间,检测各组小鼠的进食量,比色法检测各组大鼠脑组织中超氧化物歧化酶(SOD)活性和丙二醛(MDA)水平,ELISA法检测各组大鼠脑组织中肿瘤坏死因子α(TNF-α)和白细胞介素1β(IL-1β)水平。结果:与模型组比较,各剂量抑眩宁颗粒组和阳性对照组小鼠和大鼠跳台逃避时间缩短(P<0.05或P<0.01),各组小鼠进食量增多;与模型组比较,各剂量抑眩宁颗粒组大鼠脑组织中SOD明显升高(P<0.05或P<0.01),各剂量抑眩宁颗粒组大鼠脑组织中MDA水平明显降低(P<0.01)。与模型组比较,中和高剂量抑眩宁颗粒组大鼠脑组织中TNF-α和IL-1β水平明显降低(P<0.05或P<0.01)。结论:抑眩宁颗粒可抑制缺血性眩晕大鼠脑组织中的炎症损伤,降低氧化应激反应,从而对缺血性眩晕发挥治疗作用。
Objective:To investigate the therapeutic effects of YiXuanNing Granule on the ischemic vertigo of the mice and rats,and to clarify its effects on the inflammation damage and oxidative stress in brain tissue of the mice and rats.Methods:The vertigo models of mice and rats were established by mechanical vertigo and ligation of bilateral common carotid arteries(CCA),respectively.A total of 60 mice and 60 rats were selected and randomly divided into normal control group,model group,low dose of YiXuanNing Granule group(2.25 g·kg~(-1)/1.50 g·kg~(-1)),middle dose of YiXuanNing Granule group(4.50 g·kg~(-1)/3.00 g·kg~(-1)),high dose of YiXuanNing Granule group(9.00 g· kg~(-1)/6.00 g· kg~(-1))and positive control group(1.50 g· kg~(-1)/1.00 mg· kg~(-1) flunarizine hydrochloride capsule),and there were 10 animals in each group.The mice and the rats in control group and model group were intragastrically administered with 10 mL·kg~(-1) normal saline,and the mice and the rats in the other groups were given 10 mL·kg~(-1) corresponding drug once a day for 7 d.The escape time of jumping off the platform of the mice and the rats in various groups were determined;the food intake of the mice in various groups were detected;the activities of superoxide dismutase(SOD)and the levels of malondialdehyde(MDA)in brain tissue of the rats in various groups were detected by colorimetric method.The levels of tumor necrosis factor-α(TNF-α)and interleukin-1β(IL-1β)in brain tissue of the rats in various groups were detected by ELISA method.Results:Compared with model group,the escape time of jumping off the platform of the mice and the rats in different doses of YiXuanNing Granule groups and positive control group was shortened(P<0.05 or P<0.01),and the food intake of the mice in various groups was increased.Compared with model group,the SOD activities in brain tissue of the rats in different doses of YiXuanNing Granule groups were significantly increased(P<0.05 or P<0.01);the MDA levels in brain tissue of the rats in different doses of YiXuanNing Granule groups were significantly decreased(P<0.01);compared with model group,the levels of TNF-αand IL-1βin brain tissue of the rats and the mice in middle and high doses of YiXuanNing Granule groups were significantly decreased(P<0.05 or P<0.01).Conclusion:YiXuanNing Granule can inhibit the inflammatory damage in brain tissue of the rats with ischemic vertigo and reduce the oxidative stress,thereby,it can play a therapeutic role in ischemic vertigo.
Objective:To investigate the therapeutic effects of YiXuanNing Granule on the ischemic vertigo of the mice and rats,and to clarify its effects on the inflammation damage and oxidative stress in brain tissue of the mice and rats.Methods:The vertigo models of mice and rats were established by mechanical vertigo and ligation of bilateral common carotid arteries(CCA),respectively.A total of 60 mice and 60 rats were selected and randomly divided into normal control group,model group,low dose of YiXuanNing Granule group(2.25 g·kg~(-1)/1.50 g·kg~(-1)),middle dose of YiXuanNing Granule group(4.50 g·kg~(-1)/3.00 g·kg~(-1)),high dose of YiXuanNing Granule group(9.00 g· kg~(-1)/6.00 g· kg~(-1))and positive control group(1.50 g· kg~(-1)/1.00 mg· kg~(-1) flunarizine hydrochloride capsule),and there were 10 animals in each group.The mice and the rats in control group and model group were intragastrically administered with 10 mL·kg~(-1) normal saline,and the mice and the rats in the other groups were given 10 mL·kg~(-1) corresponding drug once a day for 7 d.The escape time of jumping off the platform of the mice and the rats in various groups were determined;the food intake of the mice in various groups were detected;the activities of superoxide dismutase(SOD)and the levels of malondialdehyde(MDA)in brain tissue of the rats in various groups were detected by colorimetric method.The levels of tumor necrosis factor-α(TNF-α)and interleukin-1β(IL-1β)in brain tissue of the rats in various groups were detected by ELISA method.Results:Compared with model group,the escape time of jumping off the platform of the mice and the rats in different doses of YiXuanNing Granule groups and positive control group was shortened(P<0.05 or P<0.01),and the food intake of the mice in various groups was increased.Compared with model group,the SOD activities in brain tissue of the rats in different doses of YiXuanNing Granule groups were significantly increased(P<0.05 or P<0.01);the MDA levels in brain tissue of the rats in different doses of YiXuanNing Granule groups were significantly decreased(P<0.01);compared with model group,the levels of TNF-αand IL-1βin brain tissue of the rats and the mice in middle and high doses of YiXuanNing Granule groups were significantly decreased(P<0.05 or P<0.01).Conclusion:YiXuanNing Granule can inhibit the inflammatory damage in brain tissue of the rats with ischemic vertigo and reduce the oxidative stress,thereby,it can play a therapeutic role in ischemic vertigo.
引文
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[6]ZHAO G C,YUAN Y L,CHAI F R,et al.Effect of Melilotus officinalis extract on the apoptosis of brain tissues by altering cerebral thrombosis and inflammatory mediators in acute cerebral ischemia[J].Biomed Pharmacother,2017,89(4):1346-1352.
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[8]徐浩锋,黄黎,史东明,等.天麻素对缺血性眩晕大鼠脑损伤保护的作用研究[J].中华危重症医学杂志:电子版,2017,10(4):261-263.
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[10]夏晖.5-HT_(1A)部分激动和5-HT重摄取抑制双靶标抗抑郁新药YL-0919的行为学评价及神经可塑性机制研究[D].北京:中国人民解放军军事医学科学院,2014.
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[12]傅继华,余书勤,刘军,等.实验性眩晕动物模型的建立[J].中国药科大学学报,2002,33(6):64-66.
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[14]刘阳,孙建宁,王堃,等.缺血性眩晕大鼠模型的建立[J].中国比较医学杂志,2013,23(1):10-13.
[15]张彩峰,张硕峰,严素玉.熄风定眩颗粒对局灶性不完全脑缺血眩晕模型大鼠的治疗作用及机制研究[J].国际药学研究杂志,2017,44(4):348-352,358.
[16]BERNARD N J.Inflammation rewires the brain[J].Nat Rev Rheumatol,2018,14(8):442.
[17]PARK J,MIN J S,KIM B,et al.Mitochondrial ROS govern the LPS-induced pro-inflammatory response in microglia cells by regulating MAPK and NF-kappaB pathways[J].Neurosci Lett,2015,584:191-196.
[18]WANG Z,ZHOU Y,YU Y,et al.Lipopolysaccharide preconditioning increased the level of regulatory B cells in the spleen after acute ischaemia/reperfusion in mice[J].Brain Res,2018,17(1):46-57.
[19]陈晨祥.小胶质细胞表达的NAMPT对脑缺血慢性期炎症的调控作用及其作用机制[D].杭州:浙江大学,2017.
[20]SURINKAEW P,SAWADDIRUK P,APAIJAI N,et al.Role of microglia under cardiac and cerebral ischemia/reperfusion(I/R)injury[J].Metab Brain Dis,2018,33(4):1019-1030.
[21]SIES H.Oxidative stress:a concept in redox biology and medicine[J].Redox Biol,2015,89(4):180-183.
[22]PAPAPETROU A,MORIS D,PATELIS N,et al.Oxidative Stress and total antioxidant status during internal carotid artery clamping with or without shunting:an experimental pilot study[J].Med Sci Monit Basic Res,2015,21(5):200-205.
[23]SINGH V,KRISHAN P,SHRI R.Antioxidant-mediated neuroprotection by Allium schoenoprasum L.leaf extract against ischemia reperfusion-induced cerebral injury in mice[J].J Basic Clin Physiol Pharmacol,2018,29(4):403-410.
[24]成佳星,徐俊,徐耀,等.脑出血后磁共振弥散加权急性小缺血病灶研究进展[J].中国实用内科杂志,2017,37(2):152-154.
[25]张楠,孙萌,王彩霞,等.缺血修饰白蛋白结合二维斑点追踪技术诊断不稳定型心绞痛临床研究[J].中国实用内科杂志,2017,37(4):339-342.
[2]LJUNGGREN M,PERSSON J,SALZER J.Dizziness and the acute vestibular syndrome at the emergency department:Apopulation-based descriptive study[J].Eur Neurol,2018,79(1/2):5-12.
[3]DONNELLY J P,CHANCELLOR A M,EL-DIEB A.Central cause of positioning vertigo[J].Pract Neurol,2018,18(6):492-493.
[4]FENG Y,LIAO S W,WEI C J,et al.Infiltration and persistence of lymphocytes during late-stage cerebral ischemia in middle cerebral artery occlusion and photothrombotic stroke models[J].J Neuroinflammation,2017,14(1):248.
[5]RONG W U,XIANGPEN L I,PENGFEI X U,et al.TREM2 protects against cerebral ischemia/reperfusion injury[J].Mol Brain,2017,10(1):20.
[6]ZHAO G C,YUAN Y L,CHAI F R,et al.Effect of Melilotus officinalis extract on the apoptosis of brain tissues by altering cerebral thrombosis and inflammatory mediators in acute cerebral ischemia[J].Biomed Pharmacother,2017,89(4):1346-1352.
[7]李桂杰,海英.眩晕中医病因病机探析[J].辽宁中医药大学学报,2017,19(9):179-182.
[8]徐浩锋,黄黎,史东明,等.天麻素对缺血性眩晕大鼠脑损伤保护的作用研究[J].中华危重症医学杂志:电子版,2017,10(4):261-263.
[9]刘红梅,司维,鲁嵒,等.眩晕的中医证候相关因素分析[J].世界科学技术-中医药现代化,2015,17(12):2553-2557.
[10]夏晖.5-HT_(1A)部分激动和5-HT重摄取抑制双靶标抗抑郁新药YL-0919的行为学评价及神经可塑性机制研究[D].北京:中国人民解放军军事医学科学院,2014.
[11]徐建新.天麻五苓散合抑眩宁治疗眩晕128例[J].浙江中医杂志,2007,42(4):207.
[12]傅继华,余书勤,刘军,等.实验性眩晕动物模型的建立[J].中国药科大学学报,2002,33(6):64-66.
[13]ZWERGAL A,M?HWALD K,DIETERICH M.Vertigo and dizziness in the emergency room[J].Nervenarzt,2017,88(6):587-596.
[14]刘阳,孙建宁,王堃,等.缺血性眩晕大鼠模型的建立[J].中国比较医学杂志,2013,23(1):10-13.
[15]张彩峰,张硕峰,严素玉.熄风定眩颗粒对局灶性不完全脑缺血眩晕模型大鼠的治疗作用及机制研究[J].国际药学研究杂志,2017,44(4):348-352,358.
[16]BERNARD N J.Inflammation rewires the brain[J].Nat Rev Rheumatol,2018,14(8):442.
[17]PARK J,MIN J S,KIM B,et al.Mitochondrial ROS govern the LPS-induced pro-inflammatory response in microglia cells by regulating MAPK and NF-kappaB pathways[J].Neurosci Lett,2015,584:191-196.
[18]WANG Z,ZHOU Y,YU Y,et al.Lipopolysaccharide preconditioning increased the level of regulatory B cells in the spleen after acute ischaemia/reperfusion in mice[J].Brain Res,2018,17(1):46-57.
[19]陈晨祥.小胶质细胞表达的NAMPT对脑缺血慢性期炎症的调控作用及其作用机制[D].杭州:浙江大学,2017.
[20]SURINKAEW P,SAWADDIRUK P,APAIJAI N,et al.Role of microglia under cardiac and cerebral ischemia/reperfusion(I/R)injury[J].Metab Brain Dis,2018,33(4):1019-1030.
[21]SIES H.Oxidative stress:a concept in redox biology and medicine[J].Redox Biol,2015,89(4):180-183.
[22]PAPAPETROU A,MORIS D,PATELIS N,et al.Oxidative Stress and total antioxidant status during internal carotid artery clamping with or without shunting:an experimental pilot study[J].Med Sci Monit Basic Res,2015,21(5):200-205.
[23]SINGH V,KRISHAN P,SHRI R.Antioxidant-mediated neuroprotection by Allium schoenoprasum L.leaf extract against ischemia reperfusion-induced cerebral injury in mice[J].J Basic Clin Physiol Pharmacol,2018,29(4):403-410.
[24]成佳星,徐俊,徐耀,等.脑出血后磁共振弥散加权急性小缺血病灶研究进展[J].中国实用内科杂志,2017,37(2):152-154.
[25]张楠,孙萌,王彩霞,等.缺血修饰白蛋白结合二维斑点追踪技术诊断不稳定型心绞痛临床研究[J].中国实用内科杂志,2017,37(4):339-342.