目的 探讨胡黄连苷Ⅱ对脑缺血/再灌注损伤后p38丝裂原活化蛋白激酶(p38 MAPK)通路的影响及其神经保护作用机制。  方法 成年健康雄性Wistar大鼠150只，应用线栓法建立大鼠大脑中动脉闭塞/再灌注（MCAO/R）模型，按照随机对照原则，动物分为假手术组、模型组、胡黄连苷组、茴香霉素（p38 MAPK激活剂）组、茴香霉素+胡黄连苷组和SB203580（p38 MAPK抑制剂）组和SB203580+胡黄连苷组。改良神经功能评分（mNSS）法评价大鼠神经行为功能，HE染色观察神经细胞的形态结构， TUNEL法检测细胞凋亡，免疫组织化学法检测脑组织磷酸化p38 MAPK(p-p38 MAPK)表达水平，Western blotting检测大鼠皮质区p-p38 MAPK、磷酸化MAPK激活的蛋白激酶2（p-MK2）、磷酸化胞质磷脂酶A2（p-cPLA2）、白细胞介素6（IL-6）和肿瘤坏死因子α（TNF-α）。  结果 假手术组大鼠无神经功能缺损。模型组大鼠神经功能缺损评分升高，皮质区神经细胞损伤加重，脑梗死体积增大，凋亡细胞增多，p-p38 MAPK、p-MK2、p-cPLA2、IL-6及TNF-α蛋白表达增强。胡黄连苷组、SB203580组和SB203580+胡黄连苷组大鼠皮质区神经元损伤较轻，凋亡细胞数量明显减少，p-p38 MAPK、p-MK2、p-cPLA2以及IL-6蛋白表达较模型组明显降低。茴香霉素组、茴香霉素+胡黄连苷组各项指标与模型组相近，脑梗死体积较大，神经功能缺损较重，p-p38 MAPK、p-MK2、p-cPLA2以及IL-6蛋白表达升高。   结论 脑缺血损伤后激活p38 MAPK信号通路介导神经元凋亡和炎症反应，胡黄连苷Ⅱ可能通过降低p38 MAPK通路的活化，抑制神经元凋亡和炎症反应从而保护神经系统。

Objective To explore the neuroprotective effect and mechanism of picroside Ⅱ on p38 mitogen activated protein kinase（p38 MAPK）signal transduction pathway after cerebral ischemia/reperfusion injury in rats.   Methods A total of 150 healthy male Wistar rats were subject to establish middle cerebral artery occlusion/reperfusion (MCAO/R) models by inserting a monofilament thread. All rats were randomly divided into sham group, model group, picroside (Picr) group, anisomycin (Anis，agonist of p38 MAPK) group, Anis+Picr group, SB203580 (SB, inhibitor of p38 MAPK) group and SB+Picr group. The neurobehavioral function was evaluated by modified neurological severity score points (mNSS) test. The structure of neuron was observed using HE staining. The apoptotic cells were counted using TUNEL assay. The expression of phosphorylated p38 MAPK (p-p38 MAPK) in cortex was determined using the immunohistochemistry. And the expressions of p-p38 MAPK, phosphorylated MAPK activated protein kinase-2 (p-MK2), phosphorylated cytoplasm phospholipase A2 (p-cPLA2), interleukin-6 (IL-6) and tumor necrotic factor α (TNF-α) were determined by Western blotting.    Results No neurological behavioral malfunction was found in sham group. In model group, the damage of neuron was worsened, while the neurobehavioral function score, apoptotic cell index and the expressions of p-p38 MAPK, p-MK2, p-cPLA2，IL-6 and TNF-α increased significantly than those in control group. No significant difference was found in TNF-α. In Picr group, SB group and SB+Picr group, the damage of neuron was lighter, the neurological behavioral function was improved, the number of apoptotic cells and the expressions of p-p38 MAPK, p-MK2, p-cPLA2 and IL-6 decreased significantly than those in model group. In Anis group and Anis+Picr group, the damage was worsen, the cerebral infarction was larger, and the expressions of p-p38 MAPK, p-MK2, p-cPLA2 and IL-6 increased significantly than those in control group.    Conclusion Picroside Ⅱ  can protect the neuron from the apoptosis and inflammation reaction after MCAO/R by inhibiting p38 MAPK signal transduction pathway in rats.