脑脉通对老龄大鼠脑缺血再灌注海马齿状回细胞增殖分化的影响及量效作用

Influence and Dose-effect of Naomaitong on Dentate Gyrus Cell Proliferation and Differentiation in Senile Rats with Cerebral Ischemia-reperfusion Lesion

目的:从海马齿状回(dentate gyrus,DG)细胞增殖和分化的变化揭示脑脉通抗老年脑缺血再灌注损伤的保护机制及其量效关系。方法:采用MCAO方法制作脑缺血(缺血3h再灌注12d)动物模型,观察脑脉通(大、中、小剂量)对脑缺血再灌注大鼠神经症状积分、脑组织含水量、病理变化、海马齿状回细胞增殖、分化及其变化的影响。结果:老龄模型组脑组织含水量、神经症状积分、Brdu阳性细胞、BrdU/NeuN双标阳性细胞、BrdU/GFAP双标阳性细胞数目均高于假手术组;脑脉通组(大、中、小剂量)、尼莫地平组脑组织含水量、神经症状积分均低于模型组,脉通组(大、中、小剂量)、尼莫地平组Brdu阳性细胞、BrdU/Ne-uN双标阳性细胞数目高于模型组,BrdU/GFAP双标阳性细胞数目低于模型组;脑脉通中剂量组神经症状积分、Brdu阳性细胞数目高于尼莫地平组;脑脉通中剂量组大鼠神经症状积分、脑组织含水量、病理变化、均低于脑脉通小剂量组,Brdu阳性细胞、BrdU/NeuN双标阳性细胞数目高于脑脉通小剂量组。结论:脑缺血可激活大鼠DG神经干细胞增殖;脑脉通拮抗脑缺血再灌注损伤机制与其促进DG区神经干细胞增殖和分化有关,且以脑脉通中剂量效果最全面。

Objective： To discover the protective mechanism and dose-effect relationship of Naomaitong in antagonzlng senile cerebral ischemia-reperfusion lesion on the base of changes of dentate gyrus cell proliferation and differentiation. Methods： The animal model of cerebral isehemia （ischemia for 3 hours, ischemia-reperfusion for 12 days） was established by using MCAO. Then observed the effect of Naomaitong （ in major, medium and small dosage） on the nerve symptom cerebral ischemia-reperfusion, brain water scores of rats with content and pathological changes, and the proliferation, differentiation and changes of dentate gyrus cell. Results： In the senile model group, the brain water content, nerve symptom scores, the number of masculine cell and Brdu/NeuN double label masculine cells and Brdu/GFAP double label masculine cells were all higher than those in the shamoperation group. In Naomaitong （high, medium and small dosage） group and the nimodipine group, the brain water content, nervous symptom scores were all lower than those of the model group. In Naomaitong group （high, medium and small dosage） and the nimodipine group, the number of Brdu cells and Brdu/NeuN double label masculine cells was higher than that in model group, but the number of Brdu/GFAP double label masculine cells lower. In the Naomaitong of medium dosage group, the nerve symptom scores and the number of Brdu masculine cells were higher than those of nimodipine group. In Naomaitong group of medium dosage, the nerve symptom scores of rats, the brain water content and pathological changes were all lower than those in Naomaitong of small dosage group, but the number of Brdu masculine cells and Brdu/NeuN double label masculine cells were higher. Conclusion： The cerebral ischemia can make active the proliferation of DG nerve trunk cells in rats. The mechanism of Naomaitong for antagonizing cerebral ischemia-reperfusion lesion is related to the proliferation and differentiation of DG nerve trunk cells, and the effect of Naomaitong in medium dosage is comprehensive.