植物雌激素对去势雌性大鼠缺血性脑损伤的神经保护作用

Neuroprotective Effects of Phytoestrogen and Estrogen against Neuronal Injury in Focal Cerebral Ischemia of Female Rats

目的对比研究植物雌激素和动物雌激素对去势雌性SD大鼠永久性局灶性脑缺血组织的神经保护作用。方法采用线栓法建立右侧永久性大脑中动脉阻断模型。缺血24h后立即断头取脑,冠状切片,HE染色后于光镜下观察缺血侧大脑皮层的病理变化,应用免疫组化法检测不同实验组大鼠缺血侧Cfos表达情况,以DNA缺口末端标记法原位检测细胞凋亡,通过TTC染色比较脑梗死体积百分比。结果动物雌激素(17β雌二醇)组及植物雌激素(葛根素)组与生理盐水组相比,光镜下正常神经细胞密度显著增加,缺血侧C-fos表达阳性的细胞数明显减少,凋亡细胞数显著减少,脑梗死体积百分比也明显缩小(P<0.05)。两种雌激素相比,上述4项指标差异均无显著性(P>0.05)。结论两种雌激素对缺血性脑损伤均有保护作用,可减弱大脑缺血梗死灶边缘区的Cfos表达,从而延缓神经细胞凋亡。这可能是雌激素脑保护作用的机制之一。

Objective To investigate the effects of estrogen and phytoestrogen in permanent focal cerebral ischemia induced by right middle artery occlusion of ovariectmized female rats. Methods Female Sprague Dawley rats were all bilaterally ovariectomized. Then it was divided into three groups randomly. Three groups were pretreated with 8.5 g/L sodium chloride injection, 17-β estradiol, puerarin intraperitoneally. One week later, the permanent right middle artery occlusion was applied in all ovariectmized female rats. After 24 hour, rats were killed. The cerebral sector histology was examined. The hormone expression with immunohistochemical methods. Coronal brain section was analysed using an in situ Cell Death detection kit, and hematoxylin and eosin. Ischemia infarct size was quantified using 2,3,5-triphenyl tetrazolium chloride (TTC) staining. Results In 17-beta estradiol and puerarin treated groups, the density of normal neurons was significantly higher than 8.5 g/L sodium chloride (P<0.05). The number of C-fos immunoreactive cells decreased in the two groups (P<0.05). DNA fragmentation was present in a lower of C-fos was analyzed level in 17-β estradiol and puerarin treated group than sham-group (P<0.05 ). The number of cells exhibiting apoptosis decreased in 17-β estradiol and puerarin treated group. The infarct volume was smaller (P<0.05). There were no significant difference between 17-β estradiol-treated group and puerarin-treated group in the density of normal neurons, the expression of C-fos, DNA fragmentation presentation and infarct size. Conclusions Both estrogen and phytoestrogen exerted neuroprotective effects in focal cerebral ischemia .The mechanism of neuroprotection may be associated with the attenuation of C-fos induction.