丁苯酞注射液对大鼠局灶性脑缺血再灌注损伤的神经保护作用

doi:10.6040/j.issn.1671-7554.0.2015.1079

摘要/Abstract

摘要： 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-1α mRNA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。

关键词: 过氧化物酶体增殖活化受体γ共激活因子-1α, 沉默信息调节因子2相关酶1, 神经保护作用, 丁苯酞, 脑缺血再灌注损伤

Abstract: Objective To explore the neuroprotective effect of dl-3n-butylphthalide(NBP)on focal cerebral ischemia reperfusion injury in rats and to investigate the possible mechanism. Methods A total of 75 male Sprague-Dawley(SD)rats were randomly divided into Sham operation group(Sham group), ischemia/reperfusion injury group(IR group), high-dose NBP post-treatment group(high-dose group), medium-dose NBP post-treatment group(medium-dose group)and low-dose NBP post-treatment group(low-dose group), with 15 rats in each group. Focal cerebral ischemia reperfusion model was established with middle cerebral artery occlusion(MCAO)by modified cerebral artery ligation. At 24 h after 2 hours reperfusion, neurological deficits and the infarct volume were measured. TdT-mediated dUTP nick-end labeling(TUNEL)was used to observe the expression of neuronal apoptosis. Immunohistochemistry was used to observe silent mating type information regulation 2 homolog 1(SIRT1)and peroxisome proliferator-activated receptor-γ coactivator-1α(PGC-1α)positive cells. Quantitative Real-time PCR was used to observe the expression of SIRT1 and PGC-1α mRNA. Results The rats in Sham group showed no obvious neurological deficit symptoms and no 山东大学学报 (医学版)54卷4期 -赵秀芹,等.丁苯酞注射液对大鼠局灶性脑缺血再灌注损伤的神经保护作用 \=-infarct size. Compared with Sham group, the number of apoptotic cells increased in IR group and three dosage levels of NBP post-treatment group(P<0.05), so were the number of SIRT1 and PGC-1α positive cells and the expression of SIRT1 and PGC-1α mRNA(P<0.05). Compared with IR group, the neurological deficit scores decreased in each three dosage level of NBP post-treatment group(P<0.05), so were the infarct size and the number of apoptotic cells(P<0.05), while the number of SIRT1 and PGC-1α positive cells and the expression of SIRT1 and PGC-1α mRNA in NBP post-treatment group were increased(P<0.05). Compared with medium- or low- dose group, the high-dose group had lowest neurological deficit scores, infarct size and the number of apoptotic cells, but highest number of SIRT1 and PGC-1α positive cells and the expression of SIRT1 and PGC-1α mRNA, with significant difference(P<0.05). Conclusion NBP injection can relieve the brain damage induced by focal cerebral ischemia reperfusion in rats, which potentially related to the up-regulation of SIRT1 and PGC-1α expression.

Key words: Butylphthalide, Focal cerebral ischemia reperfuson, Silent mating type information regulation 2 homolog 1, Peroxisome proliferator-activated receptor-γ coactivator-1α, Neuroprotective effect

中图分类号:

R743

赵秀芹,邓春颖,李世英,张晋霞,贺永贵,余红,刘斌. 丁苯酞注射液对大鼠局灶性脑缺血再灌注损伤的神经保护作用[J]. 山东大学学报（医学版）, 2016, 54(4): 25-31.

ZHAO Xiuqin, DENG Chunying, LI Shiying, ZHANG Jinxia, HE Yonggui, YU Hong, LIU Bin. Neuroprotective effect of dl-3n-butylphthalide on focal cerebral ischemia reperfusion injury in rats[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2016, 54(4): 25-31.

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