【摘要】：目的:觀察不同劑量丁苯酞(NBP)對大鼠急性腦缺血再灌注損傷后腦組織HIF-1α、Survivin的表達變化和微血管生成的影響,并探討其意義。方法:40只雄性Sprague-Dawley(SD)大鼠隨機分為5組:假手術(shù)組(對照組)、模型組(缺血再灌注組)、NBP低、中、高劑量組(治療組)(n=8),采用改良longa線栓法制作大鼠大腦中動脈缺血再灌注模型(MCAO/R),治療組于缺血2h再灌注即刻分別給予腹腔注射丁苯酞稀釋液20、40、80 mg·Kg-1,假手術(shù)組及模型組分別給予等體積的Tween80溶液。再灌注后24h采用longa 5分制法行神經(jīng)功能缺損評分,HE染色觀察各組腦組織病理形態(tài)學變化,免疫組化法檢測各組腦組織標本中HIF-1a、Survivin蛋白表達與CD31指示的腦組織缺血半暗帶區(qū)毛細血管新生的變化。結(jié)果:假手術(shù)組未見任何神經(jīng)功能缺損,半暗帶區(qū)新生毛細血管計數(shù)、HIF-1α、Survivin表達灰度值分別為2.5±1.2、174.6±9.9、163.0±5.8;模型組及治療組可見不同程度神經(jīng)功能損害,HE染色可見部分細胞空泡變性,核溶解、碎裂,其半暗帶區(qū)新生毛細血管計數(shù)分別為4.5±1.2、6.3±1.0、8.3±1.4、8.9±1.5,HIF-1a表達灰度值分別為138.9±5.0、148.4±6.4、160.8±8.1、162.0±5.3,Survivin表達灰度值分別為153.9±4.9、146.1±2.8、134.1±6.7、131.3±3.6,與假手術(shù)組比較認為差異有統(tǒng)計學意義(p0.05);與模型組比較,NBP治療組各組神經(jīng)功能評分、HIF-1α表達下降,微血管含量、Survivin表達進一步升高,不同劑量NBP組間比較,高劑量組神經(jīng)功能評分最低,中、高劑量組間差異尚不能認為有統(tǒng)計學意義(p0.05)。結(jié)論:丁苯酞可能通過調(diào)節(jié)HIF-1α、Survivin的表達,減少神經(jīng)細胞變性,促進缺血半暗帶區(qū)血管再生起到神經(jīng)保護作用,且存在最佳量效關系。
[Abstract]:Aim: to observe the effects of butyphthalide (NBP) at different doses on the expression of HIF-1 偽, 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 偽 and Survivin expression were 2.5 鹵1.2174.6 鹵9.9163.0 鹵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 鹵1.2o6.3 鹵1.00.93 鹵1.48.9 鹵1.5, respectively. The gray scales of HIF-1a expression were 138.9 鹵5.0148.4 鹵6.4160.8 鹵8.1162.0 鹵5.3 respectively, 153.9 鹵4.9146.1 鹵2.8134.1 鹵6.7131.3 鹵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 偽, 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 偽 and Survivin, reducing the degeneration of nerve cells and promoting vascular regeneration in ischemic penumbra, and there is an optimal dose-effect relationship.
【學位授予單位】：山西醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R743.3

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