中国临床药理学杂志

目的 研究血府逐瘀胶囊对脑缺血大鼠神经功能、神经细胞凋亡及细胞外调节蛋白激酶(ERK)/丝裂原活化蛋白激酶(MAPK)信号通路的影响。方法 选取SPF级健康雄性SD大鼠50只，随机分为对照组(10只，予以假手术，0.9%NaCl灌胃)、造模大鼠(40只，经大脑中动脉阻塞法建立脑缺血大鼠模型)。将造模成功大鼠随机分为模型组(0.9%NaCl灌胃)、XZC组(38 mg·kg^-1血府逐瘀胶囊灌胃)、西药组(12 mg·kg^-1尼莫地平灌胃)和TPA组(经脑室给予50μmol·L^-1 ERK/MAPK激活药10μL)。以四氮唑(TTC)染色法测定脑梗死面积，以Zea Longa法评估神经功能缺损程度，以原位末端标记法测定神经细胞凋亡率，以酶联免疫吸附试验测定脑组织中白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)水平，以蛋白质印迹法测定脑组织中凋亡相关蛋白及ERK/MAPK信号通路相关蛋白表达。结果 模型组、XZC组、西药组、TPA组的脑梗死面积分别为(51.47±5.29)%、(18.76±1.88)%、(19.45±2.03)%、(49.88±5.46)%;神经细胞凋亡指数分别为(20.69±2.16)%、(11.45±1.23)%、(13.18±1.52)%、(19.98±2.43)%,XZC组、西药组脑梗死面积和神经细胞凋亡指数均低于模型组、TPA组(均P<0.05)。XZC组Bax、caspase-3、p-MEK1/2及p-ERK1/2蛋白水平均低于模型组、西药组、TPA组，XZC组Bcl-2蛋白表达均高于模型组、西药组、TPA组(均P<0.05),TPA组各指标与模型组差异均无统计学意义(均P>0.05); XZC组、西药组IL-1β、IL-6、TNF-α水平均低于模型组、TPA组(均P<0.05)。结论 血府逐瘀胶囊对脑缺血大鼠神经功能有较好的保护作用，可减少其神经细胞凋亡，可能是通过抑制ERK/MAPK信号通路及炎症反应发挥作用。

Objective To study the effect of Xuefu Zhuyu capsule on nerve function,neuron apoptosis and extracellular regulated protein kinase (ERK)/mitogen-activated protein kinase (MAPK) signaling pathway in rats with cerebral ischemia.Methods A total of 50 SPF healthy male SD rats were selected and randomly divided into control group (10 rats,sham operation,intragastric administration of 0.9%NaCl) and model rats (40 rats,rat model of cerebral ischemia was constructed by middle cerebral artery occlusion).After successful molding,the rats were randomly divided into model group (intragastric administration of 0.9%NaCl),XZC group (intragastric administration of 38 mg·kg^-1Xuefu Zhuyu capsule),western medicine group (intragastric administration of 12 mg·kg^-1nimodipine) and TPA group (ventricle administration of 50μmol·L^-1ERK/MAPK activator 10μL).The cerebral infarction size was measured by tetrazolium (TTC) staining.The severity of neurological impairment was evaluated by Zea Longa method.The neuron apoptosis rate was detected by terminal-deoxynucleoitidyl transferase mediated nick end labeling.The levels of interleukin-1β (IL-1β),interleukin-6 (IL-6) and tumor necrosis factor-α(TNF-α) in brain tissue were determined by enzyme-linked immunosorbent assay.The expression of apoptosisrelated proteins and ERK/MAPK signaling pathway related proteins in brain tissues were detected by Western Blot.Results The cerebral infarction sizes in model group,XZC group,western medicine group and TPA group were(51.47±5.29)%,(18.76±1.88)%,(19.45±2.03)%and (49.88±5.46)%;the neuron apoptosis index were(20.69±2.16)%,(11.45±1.23)%,(13.18±1.52)%and (19.98±2.43)%;the cerebral infarction size and neuron apoptosis indexes in XZC group and western medicine group were lower than those in the model group and the TPA group (all P<0.05).The protein levels of Bax,caspase-3,p-MEK1/2 and p-ERK1/2 in XZC group were lower than those in model group,western medicine group and TPA group,while the protein expression of Bcl-2 in XZC group was higher than those in model group,Western medicine group and TPA group (all P<0.05).There was no significant difference between TPA group and model group (all P>0.05).The levels of IL-1β,IL-6 and TNF-α in XZC group and western medicine group were lower than those in model group and TPA group (all P<0.05).Conclusion Xuefu Zhuyu capsule can protect nerve function and reduce neuron apoptosis in rats with cerebral ischemia.The mechanism may be related to the inhibiting of ERK/MAPK signaling pathways and inflammatory response.