大黄素对缺血性脑卒中模型大鼠的神经保护作用及其对ERK1/2信号通路的影响

目的：研究大黄素对缺血性脑卒中模型大鼠的神经保护作用及其对细胞外调节蛋白激酶1/2（ERK1/2）信号通路的影响，探讨大黄素保护缺血性脑卒中的机制。方法：将200只大鼠随机分为假手术组（n=60）、模型组（n=70）和大黄素组（n=70）。模型组和大黄素组大鼠建立缺血性脑卒中模型，大黄素组大鼠在建模前30 min给予大黄素腹腔注射。评定各组大鼠神经功能障碍评分、脑梗死体积和脑组织含水量，免疫组织化学染色测定各组大鼠缺血侧脑组织皮质细胞凋亡率，Western blotting法测定各组大鼠缺血侧脑组织中Cleavedcaspase-3、Bcl-2相关X蛋白（Bax）、B淋巴细胞瘤2（Bcl-2）、ERK1/2和磷酸化-ERK1/2（p-ERK1/2）蛋白表达水平。结果：假手术组大鼠无神经功能障碍和脑梗死灶；大黄素组大鼠神经功能障碍评分和脑梗死体积均明显低于模型组（t=8.331，t=3.538，P<0.05）。与模型组比较，大黄素组大鼠脑组织含水量降低（t=9.507，P<0.05），缺血侧脑组织皮质细胞凋亡率降低（t=57.593，P<0.05），缺血侧脑组织中Cleavedcaspase-3、Bax和p-ERK1/2蛋白表达水平降低（t=4.088，t=4.463，t=10.659，P<0.05），Bcl-2蛋白表达水平升高（t=5.035，P<0.05）。结论：大黄素可能通过抑制ERK1/2信号通路抑制神经细胞凋亡发挥对缺血性脑卒中大鼠的神经保护作用。

Neuroprotective effect of emodin on ischemic stroke model rats and its effect on ERK1/2 signaling pathway

Objective: To study the neuroprotective effect of emodin in the model rats with ischemic stroke and its effect the on extracellular regulated protein kinase1/2 (ERK1/2) signaling pathway, and to explore the mechanism of protective effect of emodin on the ischemic stroke. Methods: A total of 200 rats were randomly divided into sham operation group (n=60 rats), model group (n=70) and emodin group (n=70). The rat models of ischemic stroke were established in model group and emodin group. The rats in emodin group were injected intraperitoneally with emodin 30 min before modeling. The neurological dysfunction scores, cerebral infarction volumes and water contents in brain tissue of the rats in various groups were measured; immunohistochemical staining was used to determine the apoptotic rates of ischemic lateral cortex cells of the rats in various groups;Western blotting method was used to determine the expression levels of Cleaved caspase-3, Bcl-2 related X protein (Bax), B lymphocyte tumor-2 (Bcl-2), ERK1/2 and phosphorylation-ERK1/2 (p-ERK1/2) proteins of the rats in various groups. Results: The rats in sham operation group had no neurological dysfunction and cerebral infarction. The neurological dysfunction score and cerebral infarction volume of the rats in emodin group were significantly lower than those in model group (t=8.331, t=3.538, P<0.05).Compared with model group, the water content in brain tissue of the rats in emodin group was decreased (t=9.507, P<0.05), the apoptotic rate of cerebral cortex cells was decreased (t=57.593,P<0.05), the expression levels of Cleaved caspase-3, Bax, and p-ERK1/2 proteins in ischemic brain tissue were decreased (t=4.088, t=4.463, t=10.659, P<0.05), and the expression level of Bcl-2 protein in ischemic brain tissue was increased (t=5.035, P<0.05). Conclusion: Emodin may inhibit the neuronal apoptosis by inhibiting the ERK1/2 signaling pathway to exert the neuroprotective effect on the rats with ischemic stroke.