毛冬青皂酮胶囊对大鼠短暂脑缺血发作模型的保护作用研究
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摘要
目的:通过建立大鼠TIA模型来研究毛冬青皂酮胶囊对大鼠TIA模型的保护作用。方法:采用尾静脉注射过氧化叔丁醇的方法来建立大鼠TIA模型。大鼠随机分为空白组、模型组、养血清脑颗粒组(1g/kg)、尼莫地平组(0.03g/kg)与毛冬青皂酮胶囊0.2g/kg、0.1g/kg、0.05g/kg组,各组连续给药7d。在给药第3、6d分别尾静脉注射过氧化叔丁醇,进行神经行为学评分。于末次造模的第二天灌胃1h后,测定血液流变学、血浆中溶血磷脂酸(LPA)及血清中的超敏C-反应蛋白含量;HE染色观察脑组织皮质区的病理形态变化。结果:与模型组相比,大、中剂量毛冬青皂酮胶囊组均可显著降低大鼠神经行为学评分,并显著降低死亡率,毛冬青皂酮胶囊各剂量组对大鼠血液流变学指标均有明显的改善作用,还可显著降低大鼠血浆中LPA水平及血清中超敏C-反应蛋白水平,减轻大脑皮层神经细胞病理变化。结论:毛冬青皂酮胶囊对大鼠短暂脑缺血发作模型具有保护作用,其作用机制可能与抑制血小板的聚集,抑制炎症发生有关。
Objective: To study the protective effect of saponins and flavonoids capsule from Ilex pubescens root in established rat TIA model.Methods: TIA models of rats were established by injection of TBHP in the tail vein. Rats were randomly divided into the control group,the model group,Yangxue Qingnao granule group(1 g/kg),Nimodipine group(0. 03 g/kg),high dose of saponins and flavonoids capsule group(0. 2 g/kg),middle dose of saponins and flavonoids capsule group(0. 1 g/kg),and small dose of saponins and flavonoids capsule group(0.05 g/kg). Rats in all groups were administered for continuous 7 d. Neurobehavior scores were determined after injection of tert-butanol on third and sixth administration,respectively. On the second day after the last injection,the hemorrheology,contents of plasma lysophosphatidic acid(LPA) and hypersensitivity C-reactive protein in serum were measured,and pathological changes of cerebral cortex were observed by HE staining. Results: Compared with the model group,large and medium doses of saponins and flavonoids capsule from Ilex pubescens root significantly reduced the neurobehavior score and reduced the mortality of TIA rats(P < 0. 01). Saponins and flavonoids capsule from Ilex pubescens root in all doses of group also significantly improved the hemorrheology index,and also significantly reduced the level of LPA in plasma and the serum high sensitivity C-reactive protein level(P < 0. 01),and alleviated pathological changes of cerebral cortex neurons. Conclusion: Saponins and flavonoids capsule from Ilex pubescens root has the protective effect on rats with transient ischemic attack,and its mechanism may be related to inhibiting platelet aggregation and inflammation.
Objective: To study the protective effect of saponins and flavonoids capsule from Ilex pubescens root in established rat TIA model.Methods: TIA models of rats were established by injection of TBHP in the tail vein. Rats were randomly divided into the control group,the model group,Yangxue Qingnao granule group(1 g/kg),Nimodipine group(0. 03 g/kg),high dose of saponins and flavonoids capsule group(0. 2 g/kg),middle dose of saponins and flavonoids capsule group(0. 1 g/kg),and small dose of saponins and flavonoids capsule group(0.05 g/kg). Rats in all groups were administered for continuous 7 d. Neurobehavior scores were determined after injection of tert-butanol on third and sixth administration,respectively. On the second day after the last injection,the hemorrheology,contents of plasma lysophosphatidic acid(LPA) and hypersensitivity C-reactive protein in serum were measured,and pathological changes of cerebral cortex were observed by HE staining. Results: Compared with the model group,large and medium doses of saponins and flavonoids capsule from Ilex pubescens root significantly reduced the neurobehavior score and reduced the mortality of TIA rats(P < 0. 01). Saponins and flavonoids capsule from Ilex pubescens root in all doses of group also significantly improved the hemorrheology index,and also significantly reduced the level of LPA in plasma and the serum high sensitivity C-reactive protein level(P < 0. 01),and alleviated pathological changes of cerebral cortex neurons. Conclusion: Saponins and flavonoids capsule from Ilex pubescens root has the protective effect on rats with transient ischemic attack,and its mechanism may be related to inhibiting platelet aggregation and inflammation.
引文
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4 曹利华,郑雁,辛卫云,等.毛冬青总黄酮对小鼠血瘀合并脑缺血耐受模型的影响.中国中药杂志,2016;41(18)∶3419~3424
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8 Dussaux,C.Brunner,C.Isabel,C.et al.Functional Ultrasound(FUS)Imaging of Brain Hemodynamics in a rat Middle-Cerebral Artery Occlusion(MCAO)Model of Selective Neuronal Loss(SNL)Mimicking Transient Ischemic Attack(TIA).Journal of Cerebral Blood Flow and Metabolism,2016;36∶776
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10 张帆,张小磊,苗明三.毛冬青总黄酮对小鼠脑缺血模型的影响.中药新药与临床药理,2012;23(4)∶409~412
11 曹光秀,李然然,刘洁,等.β-石竹烯通过抗氧化作用减轻局灶性脑缺血再灌注大鼠大脑皮质损伤.中药药理与临床,2016;32(1)∶56~59
12 项丽玲,苗明三,王灿,等.基于中西医临床病症特点的短暂性脑缺血发作的动物模型分析.中国中药杂志,2017;42(14)∶2824~2828
13 蔡冰冰,郭勇,杨自更.活血通络清脑饮对老年短暂性脑缺血发作患者血液流变学、血液黏度及脑血流动力学的影响.现代中西医结合杂志,2017;26(8)∶854~856
14 李航.血浆LP-PLA2、GMP、LPA及血小板活化指标与短暂性脑缺血发作的关系.海南医学院学报,2015;21(8)∶1134~1136+1139
15 李晓萍,詹细平,楼小亮.短暂性脑缺血发作ABCD2评分与血浆LPA水平的相关性研究.山东医药,2010;50(40)∶34~35
16 王坤,王文明,盛玉国,等.超敏C反应蛋白在短暂性脑缺血发作患者临床转归中的应用.当代医学,2011;17(22)∶14~15
17 田强,沈云峰,张洪波,等.脑血管疾病患者测定血清同型半胱氨酸与超敏C-反应蛋白的临床意义.江汉大学学报(自然科学版),2010;38(1)∶94~96
2 李向荣.毛冬青药理作用研究概述.环球中医药,2011;4(3)∶238~240
3 熊天琴,陈元元,李红侠,等.毛冬青皂苷B3的抗血栓作用研究.中草药,2012;43(9)∶1785~1788
4 曹利华,郑雁,辛卫云,等.毛冬青总黄酮对小鼠血瘀合并脑缺血耐受模型的影响.中国中药杂志,2016;41(18)∶3419~3424
5 程晓,张小磊,苗明三.毛冬青总黄酮对大鼠脑缺血模型的影响.中药新药与临床药理,2012;23(6)∶640~643
6 刘亚敏,吴宿慧,李寒冰,等.大鼠脑缺血模型的研究进展.中国西部科技,2013;12(4)∶66+73
7 Durukan Tolvanen,Tatlisumak,Pedrono,et al.TIA model is attainable in Wistar rats by intraluminal occlusion of the MCA for 10 min or shorter.Brain Research,2017;1663∶166~173
8 Dussaux,C.Brunner,C.Isabel,C.et al.Functional Ultrasound(FUS)Imaging of Brain Hemodynamics in a rat Middle-Cerebral Artery Occlusion(MCAO)Model of Selective Neuronal Loss(SNL)Mimicking Transient Ischemic Attack(TIA).Journal of Cerebral Blood Flow and Metabolism,2016;36∶776
9 张帆,张小磊,苗明三.毛冬青总黄酮对大鼠血瘀合并脑缺血模型的影响.中国实验方剂学杂志,2012;18(22)∶187~191
10 张帆,张小磊,苗明三.毛冬青总黄酮对小鼠脑缺血模型的影响.中药新药与临床药理,2012;23(4)∶409~412
11 曹光秀,李然然,刘洁,等.β-石竹烯通过抗氧化作用减轻局灶性脑缺血再灌注大鼠大脑皮质损伤.中药药理与临床,2016;32(1)∶56~59
12 项丽玲,苗明三,王灿,等.基于中西医临床病症特点的短暂性脑缺血发作的动物模型分析.中国中药杂志,2017;42(14)∶2824~2828
13 蔡冰冰,郭勇,杨自更.活血通络清脑饮对老年短暂性脑缺血发作患者血液流变学、血液黏度及脑血流动力学的影响.现代中西医结合杂志,2017;26(8)∶854~856
14 李航.血浆LP-PLA2、GMP、LPA及血小板活化指标与短暂性脑缺血发作的关系.海南医学院学报,2015;21(8)∶1134~1136+1139
15 李晓萍,詹细平,楼小亮.短暂性脑缺血发作ABCD2评分与血浆LPA水平的相关性研究.山东医药,2010;50(40)∶34~35
16 王坤,王文明,盛玉国,等.超敏C反应蛋白在短暂性脑缺血发作患者临床转归中的应用.当代医学,2011;17(22)∶14~15
17 田强,沈云峰,张洪波,等.脑血管疾病患者测定血清同型半胱氨酸与超敏C-反应蛋白的临床意义.江汉大学学报(自然科学版),2010;38(1)∶94~96