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目的氧化应激(oxidative stress,OS)在缺血性脑卒中病程中起到关键作用。葡萄籽原花青素提取物(grape seed procyanidin extract,GSPE)是OS的重要调节剂。我们猜想GSPE可以保护缺血缺氧性脑损伤。本研究旨在探索GSPE能否在小鼠的缺血再灌注脑损伤起保护作用。方法对于接受GSPE注射(MCAOG,n=60)和生理盐水注射(MCAONS,n=60)的小鼠,制作短暂性大脑中动脉栓塞(transient middle cerebral artery occlusion,MCAO)模型。设置假手术组小鼠(GSPE组和生理盐水组)作为对照。采用改良的神经损害评分(m NSS)评估并比较MCAO造模后1小时、24小时、3天、7天的神经功能损害情况。在MCAO造模24小时后行3T动物颅脑核磁共振(T2WI)扫描,评估并比较梗死灶体积差异。在MCAO造模24小时后,对脑组织行神经元细胞核抗体(Neu N)、CD34、Bcl-2和Bax,以及脑组织中谷胱甘肽过氧化物酶(glutathione peroxidation,GSH-Px))和丙二醛(MDA)进行免疫组化分析。对以上指标都在各组之间的差异进行统计学分析。结果在MCAO造模24小时及之后,MCAOG组小鼠神经功能恢复好于MCAONS组小鼠(p<0.05)在MCAO造模24小时,MCAOG组小鼠脑梗塞灶体积明显小于MCAONS组小鼠(22.46±11.45 mm3 vs.47.84±9.06 mm3,P<0.05);MCAOG小鼠梗塞灶周边区域Neu N和CD34阳性染色细胞数目明显多于MCAONS小鼠(p<0.05)。MCAONS组小鼠Bax阳性染色细胞数目明显多于MCAOG组(p<0.05)。MCAOG组小鼠脑组织中平均MDA水平明显低于MCAONS组(P<0.05),GSH-Px活力明显高于MCAONS组(p<0.05)。结论 GSPE可抑制小鼠缺血再灌注脑损伤的病程。其机制可能与GSPE抑制了病程中氧化应激和凋亡反应,促进了微血管生成,以及激活抗氧化酶(GSH-Px)有关。GSPE可能代表了一种治疗缺血再灌注脑损伤的新方向。
Purpose Oxidative stress (OS) plays a key role in the course of ischemic stroke. Grape seed procyanidin extract (grape seed procyanidin extract, GSPE) is an important regulator of OS. We hypothesized that GSPE could protect hypoxic-ischemic brain damage. This study aimed to explore whether GSPE can protect mice from cerebral ischemia-reperfusion injury. Methods A transient middle cerebral artery occlusion (MCAO) model was made in mice receiving GSPE injection (MCAOG, n = 60) and saline injection (MCAONS, n = 60). Sham-operated mice (GSPE group and saline group) were set as controls. Neurological impairment was assessed and compared at 1 hour, 24 hours, 3 days, and 7 days after MCAO modeling using a modified neurological damage score (m NSS). A 3T animal brain scan (T2WI) scan was performed 24 hours after MCAO modeling to assess and compare infarct volume differences. Twenty-four hours after modeling of MCAO, neuronal nuclear antibodies (Neu N), CD34, Bcl-2 and Bax, and glutathione peroxidation (GSH-Px) in brain tissue Malondialdehyde (MDA) was detected by immunohistochemistry. The above indicators are statistically different between the groups. Results The neurological function of mice in MCAOG group recovered better than that in MCAONS group (P <0.05) 24 hours after MCAO modeling, the volume of cerebral infarction in mice in MCAOG group was significantly smaller than that in MCAONS group 22.46 ± 11.45 mm3 vs.47.84 ± 9.06 mm3, P <0.05). The numbers of Neu N and CD34 positive cells in infarcted zone of MCAOG mice were more than that of MCAONS mice (p <0.05). The number of Bax positive cells in MCAONS group was significantly more than that in MCAOG group (p <0.05). The average level of MDA in MCAOG group was significantly lower than that in MCAONS group (P <0.05). The activity of GSH-Px in MCAOG group was significantly higher than that in MCAONS group (p <0.05). Conclusion GSPE can inhibit the course of ischemia-reperfusion brain injury in mice. Its mechanism may be related to the inhibition of GSPE during the course of oxidative stress and apoptosis, promoting angiogenesis and activating antioxidant enzyme (GSH-Px). GSPE may represent a new direction for the treatment of ischemic reperfusion brain injury.