萨丽波+李宇

【摘要】 目的 觀察丁苯酞对大鼠局灶性脑缺血再灌注损伤后Bcl-2蛋白表达的影响及其神经保护机制。方法 60只健康SD大鼠， 制备大鼠大脑中动脉缺血再灌注模型， 造模成功2 h后拔除线栓， 再灌注， 将造模成功的SD大鼠随机分为丁苯酞治疗组、缺血再灌注组及假手术组， 每组20只。缺血再灌注组和假手术组按照150 mg/kg给予生理盐水， 丁苯酞治疗组在造模后2 h以同等剂量通过腹腔注射丁苯酞注射液。各组大鼠神经功能缺损评分均在麻醉苏醒后进行；在各组中各随机选取10只大鼠， 通过TTC染色观察脑梗死体积；各组余下大鼠进行免疫组化检测， 观察Bcl-2蛋白表达的变化。

结果 三组神经功能缺损评分、脑梗死体积比较差异均具有统计学意义（P<0.05）；缺血再灌注组及丁苯酞治疗组神经功能缺损评分、脑梗死体积均高/大于假手术组， 差异均具有统计学意义（P<0.05）。三组Bcl-2蛋白表达阳性率比较差异具有统计学意义（P<0.05）；缺血再灌注组及丁苯酞治疗组Bcl-2蛋白表达阳性率（20.12±3.36）%、（26.18±2.85）%均高于假手术组（3.15±0.42）%， 差异均具有统计学意义（P<0.05）；丁苯酞治疗组Bcl-2蛋白表达阳性率高于缺血再灌注组， 差异具有统计学意义（P<0.05）。结论 丁苯酞注射液对于大鼠缺血性脑损伤治疗有效， 可以减轻大鼠脑缺血再灌注损伤的程度， 具有神经保护作用， 其作用机制可能与Bcl-2蛋白表达相关， 并能延长缺血再灌注治疗时间窗。

【关键词】 丁苯酞；脑缺血再灌注损伤；Bcl-2蛋白

DOI：10.14163/j.cnki.11-5547/r.2017.31.113

【Abstract】 Objective To observe the effect of butylphthalide on the expression of Bcl-2 protein after cerebral ischemia reperfusion injury in rats and its neuroprotective mechanism. Methods A total of 60 healthy SD rats were used to prepare rat middle cerebral artery ischemia-reperfusion model. After 2 h of successful model， the suture was removed for reperfusion， and the successful model of SD rats were randomly divided into butylphthalide treatment group， ischemia reperfusion group and sham operation group， with 20 rats in each group. The ischemia reperfusion group and sham operation group was treated with normal saline and butylphthalide by 150 mg/kg， and butylphthalide treatment group received intraperitoneal injection of butylphthalide at the same dose 2 h after molding. The neurological deficit scores of all groups were performed after the recovery of anesthesia. 10 rats were randomly selected in each group， and the volume of cerebral infarction was observed by TTC staining. The remaining rats in each group were detected by immunohistochemistry， and the changes of Bcl-2 protein expression were observed. Results Three groups had statistically significant difference in neurological deficit score and cerebral infarction volume （P<0.05）. Ischemia reperfusion group and butylphthalide treatment group had higher/larger neurological deficit score and cerebral infarction volume than sham operation group， and the difference was statistically significant （P<0.05）. Three groups had statistically significant difference in positive rate of Bcl-2 protein expression （P<0.05）. Ischemia reperfusion group and butylphthalide treatment group had higher positive rate of Bcl-2 protein expression as （20.12±3.36）% and （26.18±2.85）% than （3.15±0.42）% in sham operation group， and their difference was statistically significant （P<0.05）. Butylphthalide treatment group had higher positive rate of Bcl-2 protein expression than ischemia reperfusion group， and the difference was statistically significant （P<0.05）. Conclusion Butylphthalide injection is effective in treating ischemic brain injury in rats. It can reduce the degree of cerebral ischemia-reperfusion injury in rats and has neuroprotective effect. Its mechanism may be related to the expression of Bcl-2 protein and it also can prolong the time window of ischemia - reperfusion therapy.endprint

【Key words】 Butylphthalide； Cerebral ischemia reperfusion injury； Bcl-2 protein

近年来， 缺血性脑血管病发病率越来越高， 已经严重威胁人类的健康。研究表明， 丁苯酞可以阻断缺血性脑损伤的多个病理生理环节， 对缺血性脑血管病具有明确有效的治疗作用[1]。缺血性脑血管病的主要病理基础是脑缺血再灌注损伤， 而神经细胞凋亡是导致发病的主要机制之一。目前研究的热点是通过何种途径减轻神经细胞凋亡从而达到治疗的目的。本研究通过注射丁苯酞对大鼠局灶性脑缺血再灌注部位进行干预， 观察其疗效及对Bcl-2蛋白表达的影响， 分析丁苯酞治疗缺血性脑损伤的作用机制， 为临床治疗脑梗死提供理论基础。

1 材料与方法

1. 1 实验动物、药物与建立缺血再灌注模型 健康雄性SD大鼠60只， 平均体重（250±50）g， 购置于沈阳医学院动物实验中心。……