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目的探讨丁苯酞(NBP)注射液对大鼠局灶性脑缺血再灌注损伤的神经保护作用及可能机制。方法将雄性Sprague-Dawley(SD)大鼠75只随机分为假手术组(Sham组)、脑缺血组(IR组)、NBP高剂量后处理组(高剂量组)、NBP中剂量后处理组(中剂量组)和NBP低剂量后处理组(低剂量组),每组15只。采用改良线栓法制备大鼠大脑中动脉局灶性脑缺血再灌注(MACO)模型。缺血2 h后再灌注24 h,行神经功能缺损评分及脑梗死体积测定。原位末端标记法(TUNEL)检测脑梗死灶周围组织神经细胞凋亡;免疫组织化学染色法检测沉默信息调节因子2相关酶1(SIRT1)、过氧化物酶体增殖活化受体γ共激活因子-1α(PGC-1α)阳性细胞;实时荧光定量PCR法检测SIRT1、PGC-1αmRNA的表达。结果 Sham组未见神经功能缺损症状及脑梗死体积。与Sham组比较,IR组、3个剂量的NBP后处理组凋亡细胞数增多,SIRT1、PGC-1α阳性细胞数及mRNA的表达增多(P均<0.05)。与IR组比较,3个剂量的NBP后处理组神经功能评分降低,脑梗死体积、凋亡细胞数减少,SIRT1、PGC-1α阳性细胞数及mRNA的表达增多(P均<0.05)。不同剂量NBP后处理组间比较,高剂量组神经功能评分最低,脑梗死体积、凋亡细胞数最少,SIRT1、PGC-1α阳性细胞数及mRNA表达最多(P<0.05)。结论 NBP能减轻大鼠脑缺血再灌注损伤,发挥脑保护作用,其机制可能与SIRT1、PGC-1α表达上调有关。
Objective To investigate the neuroprotective effect of butylphthalide (NBP) injection on focal cerebral ischemia-reperfusion injury in rats and its possible mechanism. Methods Seventy-five male Sprague-Dawley rats were randomly divided into Sham group, IR group, NBP high-dose group (high-dose group), NBP medium-dose group Group (middle dose group) and NBP low dose post-treatment group (low dose group), 15 rats in each group. The middle cerebral artery occlusion (MCAO) model of focal cerebral ischemia-reperfusion (MACO) was established by modified suture method. After 2 h of ischemia and reperfusion 24h, neurological deficit score and cerebral infarction volume were measured. TUNEL method was used to detect neuronal apoptosis in the surrounding tissue of cerebral infarction. Immunohistochemical staining was used to detect the expression of SIRT1 and peroxisome proliferator-activated receptor gamma coactivator -1α (PGC-1α) positive cells. Real-time fluorescence quantitative PCR was used to detect the expression of SIRT1 and PGC-1αmRNA. Results Sham group showed no symptoms of neurological deficit and cerebral infarction volume. Compared with Sham group, the number of apoptotic cells and the number of SIRT1, PGC-1α positive cells and mRNA expression increased in IR group and NBP-treated group (P <0.05). Compared with the IR group, the neurological scores decreased, the volume of cerebral infarction, the number of apoptotic cells, the number of SIRT1, PGC-1α positive cells and the mRNA expression increased (P <0.05). Compared with the NBP post-treatment group, the neurological score, the volume of cerebral infarction and the number of apoptotic cells in the high-dose group were the lowest, the number of SIRT1 and PGC-1α positive cells and mRNA expression were the highest (P <0.05). Conclusion NBP attenuates cerebral ischemia-reperfusion injury in rats and exerts neuroprotective effects. The mechanism may be related to the up-regulation of SIRT1 and PGC-1α.