不同剂量丁苯酞对大鼠急性脑缺血再灌注损伤后HIF-1α、Survivin表达及血管再生的影响

发布时间：2018-10-25 18:54

【摘要】：目的:观察不同剂量丁苯酞(NBP)对大鼠急性脑缺血再灌注损伤后脑组织HIF-1α、Survivin的表达变化和微血管生成的影响,并探讨其意义。方法:40只雄性Sprague-Dawley(SD)大鼠随机分为5组:假手术组(对照组)、模型组(缺血再灌注组)、NBP低、中、高剂量组(治疗组)(n=8),采用改良longa线栓法制作大鼠大脑中动脉缺血再灌注模型(MCAO/R),治疗组于缺血2h再灌注即刻分别给予腹腔注射丁苯酞稀释液20、40、80 mg·Kg-1,假手术组及模型组分别给予等体积的Tween80溶液。再灌注后24h采用longa 5分制法行神经功能缺损评分,HE染色观察各组脑组织病理形态学变化,免疫组化法检测各组脑组织标本中HIF-1a、Survivin蛋白表达与CD31指示的脑组织缺血半暗带区毛细血管新生的变化。结果:假手术组未见任何神经功能缺损,半暗带区新生毛细血管计数、HIF-1α、Survivin表达灰度值分别为2.5±1.2、174.6±9.9、163.0±5.8;模型组及治疗组可见不同程度神经功能损害,HE染色可见部分细胞空泡变性,核溶解、碎裂,其半暗带区新生毛细血管计数分别为4.5±1.2、6.3±1.0、8.3±1.4、8.9±1.5,HIF-1a表达灰度值分别为138.9±5.0、148.4±6.4、160.8±8.1、162.0±5.3,Survivin表达灰度值分别为153.9±4.9、146.1±2.8、134.1±6.7、131.3±3.6,与假手术组比较认为差异有统计学意义(p0.05);与模型组比较,NBP治疗组各组神经功能评分、HIF-1α表达下降,微血管含量、Survivin表达进一步升高,不同剂量NBP组间比较,高剂量组神经功能评分最低,中、高剂量组间差异尚不能认为有统计学意义(p0.05)。结论:丁苯酞可能通过调节HIF-1α、Survivin的表达,减少神经细胞变性,促进缺血半暗带区血管再生起到神经保护作用,且存在最佳量效关系。
[Abstract]:Aim: to observe the effects of butyphthalide (NBP) at different doses on the expression of HIF-1 伪, Survivin and microangiogenesis after acute cerebral ischemia-reperfusion injury in rats, and to explore its significance. Methods: forty male Sprague-Dawley (SD) rats were randomly divided into 5 groups: sham operation group (control group), model group (ischemia / reperfusion group), low, middle and high dose group (treatment group) (n = 8). The rat model of middle cerebral artery ischemia-reperfusion (MCAO/R) was established by modified longa thread embolization method. The treatment group was given intraperitoneal injection of butyrophthalide diluent 2040 ~ 80 mg Kg-1, immediately after 2 h ischemia and reperfusion. Sham-operated group and model group were given equal volume of Tween80 solution. At 24 hours after reperfusion, the nerve function defect score was evaluated by longa 5 score, the pathological morphology of brain tissue was observed by HE staining, and the HIF-1a, in brain tissue was detected by immunohistochemical method. Expression of Survivin protein and changes of capillary neovascularization in ischemic penumbra indicated by CD31. Results: in the sham-operation group, there was no nerve function defect, the neovascularization count in the penumbra, the gray level of HIF-1 伪 and Survivin expression were 2.5 卤1.2174.6 卤9.9163.0 卤5.8, respectively. In the model group and the treatment group, different degrees of neurological damage were observed, and some of the cells were vacuolar degeneration, nuclear dissolution and fragmentation by HE staining. The neovascularization count in the penumbra was 4.5 卤1.2o6.3 卤1.00.93 卤1.48.9 卤1.5, respectively. The gray scales of HIF-1a expression were 138.9 卤5.0148.4 卤6.4160.8 卤8.1162.0 卤5.3 respectively, 153.9 卤4.9146.1 卤2.8134.1 卤6.7131.3 卤3.6, respectively. Compared with sham-operation group, the difference was statistically significant (p0.05). Compared with the model group, the nerve function score, the expression of HIF-1 伪, the microvessel content and the expression of Survivin in the NBP treatment group were lower than those in the model group. The nerve function score in the high dose group was the lowest and the middle in the high dose group, compared with the model group. The difference between high dose groups was not statistically significant (p 0.05). Conclusion: butyphthalide may play a neuroprotective role by regulating the expression of HIF-1 伪 and Survivin, reducing the degeneration of nerve cells and promoting vascular regeneration in ischemic penumbra, and there is an optimal dose-effect relationship.
【学位授予单位】：山西医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R743.3

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