三羟异黄酮对永久性脑梗死大鼠的神经保护作用及对神经干细胞增生的影响

Neuroprotective effect of genistein on pMCAO rats and ist influence on the proliferation of neural stem cells

目的研究三羟异黄酮(GST)对永久性大脑中动脉栓塞(pMCAO)模型大鼠的神经保护作用,及其对神经干细胞增生及神经再生相关因子含量的影响。方法将大鼠随机分为假手术组、对照组、GST治疗组,制作pM-CAO模型,治疗组于术后3 h腹腔注射GST 50、100μg/(kg.d),连续注射5 d,对照组注射等量生理盐水。采用神经行为学评分、脑梗死体积测定、尼氏染色、BrdU-Nestin免疫荧光双标ELISA等方法,观察GST对大鼠神经损伤、功能恢复、脑内相关部位神经干细胞增生、神经再生相关因子表达水平的影响。结果与对照组相比,GST治疗组神经行为学评分明显提高,神经干细胞数目明显增多,神经再生相关因子含量明显升高(P<0.05或<0.01)。结论 GST治疗能改善pMCAO大鼠神经行为学评分,减少脑梗死体积,进一步增加增生的神经干细胞数目及神经再生相关因子的含量,对脑组织具有神经保护作用。

Objective To investigate the neuroprotective effect of genistein （GST） and its influences on the prolifera- tion of neural stem cells and the expression of neuroregeneration-related factors in brain tissue of rats with permanent middle cerebral artery occlusion （pMCAO）. Methods Adult male SD rats were subjected to permanent middle cerebral artery oc- clusion （pMCAO） and randomly divided into the sham-operation group, control group and GST-treated group. GST was in- traperitoneally injected for 5 days at a dose of 50 or 100μg/（ kg · d） , 3 h after pMCAO. The control group was injected with the same dose of normal saline. TTC staining, Nissl staining, BrdU/nestin immunofluorescent double staining of neu- ral stem cells （NSCs） and ELISA methods were conducted to determine the influence of GST on the neurological function, the proliferation of NSCs, and the expression of neuroregeneration-related factors in brain tissue. Results Compared with the control group, the neurological behavior score, the number of BrdU/nestin-positive cells and the expression level of neuroregeneration-related factors in the brain tissue after pMCAO in the GST-treated group were much higher （ P 〈 0.05, or 〈 0.01 ）. Conclusions GST can improve the neurological behavior score, reduce the infarct volume and promote the pro- liferation of the endogenous NSCs and the expression of neuroregeneration-related factors in the brain tissue of pMCAO rats, meanwhile it has neuroprotective effect on the brain tissue.