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Effect of Combination Therapy with Sodium Ozagrel and Panax Ginseng on Transient Cerebral Ischemia Model in Rats

机译:奥扎格雷钠与人参混合疗法对大鼠短暂性脑缺血的影响

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摘要

Sodium ozagrel (SO) prevents platelet aggregation and vasoconstriction in the cerebral ischemia. It plays an important role in the prevention of brain damage induced by cerebral ischemia/reperfusion. Recently, many animal studies have suggested that the Panax ginseng (PG) has neuroprotective effects in the ischemic brain. In this study, we assessed the neuroprotective effects that come from a combination therapy of SO and PG in rat models with middle cerebral artery occlusion (MCAO). Animals with MCAO were assigned randomly to one of the following four groups: (1) control (Con) group, (2) SO group (3 mg/kg, intravenously), (3) PG group (200 mg/kg, oral feeding), and (4) SO + PG group. The rats were subjected to a neurobehavior test including adhesive removal test and rotarod test at 1, 3, 7, 10, and 15 days after MCAO. The cerebral ischemic volume was quantified by Metamorph imaging software after 2-3-5-triphenyltetrazolium (TTC) staining. The neuronal cell survival and astrocytes expansion were assessed by immunohistofluorescence staining. In the adhesive removal test, the rats of PG or SO + PG group showed significantly better performance than those of the control group (Con: 88.1 ± 24.8, PG: 43.6 ± 11, SO + PG: 11.8 ± 7, P < .05). Notably, the combination therapy group (SO + PG) showed better performance than the SO group alone (SO: 56 ± 12, SO + PG: 11.8 ± 7, P < .05). In TTC staining for infarct volume, cerebral ischemic areas were also significantly reduced in the PG group and SO + PG group (Con: 219 ± 32, PG: 117 ± 8, SO + PG: 99 ± 11, P < .05). Immunohistofluorescence staining results showed that the group which received SO + PG group therapy had neuron cells in the normal range. They also had a low number of astrocytes and apoptotic cells compared with the control or SO group in the peri-infarction area. During astrocytes staining, compared to the SO + PG group, the PG group showed only minor differences in the number of NeuN-positive cells and quantitative analysis of infarct volume. In conclusion, these studies showed that in MCAO rat models, the combination therapy with SO and PG may provide better neuroprotective effects such as higher neuronal cell survival and inhibition of astrocytes expansion than monotherapy with SO alone.
机译:奥扎格雷钠(SO)可以预防脑缺血中的血小板聚集和血管收缩。它在预防由脑缺血/再灌注引起的脑损伤中起重要作用。最近,许多动物研究表明人参(PG)对缺血性脑具有神经保护作用。在这项研究中,我们评估了SO和PG联合治疗对大脑中动脉闭塞(MCAO)大鼠模型的神经保护作用。患有MCAO的动物随机分为以下四组之一:(1)对照组(Con)组,(2)SO组(3μmg/ kg,静脉内),(3)PG组(200μmg/ kg,口服) ),以及(4)SO + PG组。在MCAO后1、3、7、10和15天,对大鼠进行神经行为测试,包括脱胶测试和旋转脚踏测试。在2-3-5-三苯四唑(TTC)染色后,通过Metamorph成像软件对脑缺血体积进行定量。通过免疫组织荧光染色评估神经元细胞存活和星形胶质细胞扩张。在脱胶试验中,PG或SO + PG组的大鼠表现出比对照组明显更好的性能(Con:88.1±24.8,PG:43.6±11,SO + PG:11.8±7,P <.05 )。值得注意的是,联合治疗组(SO + PG)表现出比单独的SO组更好的表现(SO:56±12,SO + PG:11.8±7,P <.05)。在TTC染色中发现梗死体积,PG组和SO + PG组的脑缺血面积也显着减少(Con:219±32,PG:117±8,SO + PG:99±11,P <.05)。免疫组织荧光染色结果显示,接受SO + PG组治疗的组的神经元细胞处于正常范围。与梗死周围区域的对照组或SO组相比,它们的星形胶质细胞和凋亡细胞数量也少。在星形胶质细胞染色期间,与SO + PG组相比,PG组在NeuN阳性细胞数量和梗死体积的定量分析方面仅表现出很小的差异。总之,这些研究表明,在MCAO大鼠模型中,SO和PG的联合治疗可能比单独使用SO的单一治疗提供更好的神经保护作用,例如更高的神经元细胞存活率和星形胶质细胞扩张抑制作用。

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