【摘要】：目的通過建立家兔腦出血的模型，，探討立體定向微創(chuàng)血腫清除術(shù)在不同時間段清除顱內(nèi)血腫結(jié)合羅格列酮病灶區(qū)灌注治療顱內(nèi)血腫的不同療效，為臨床選擇立體定向微創(chuàng)血腫清除術(shù)結(jié)合羅格列酮治療腦出血的最佳治療時間窗提供實驗依據(jù)。方法共選取健康新西蘭大白兔84只，體重為2.8-3.4公斤（雌雄不分），通過立體定向技術(shù)構(gòu)建自體動脈血腦出血模型，模型構(gòu)建成功后隨機分成正常對照組、模型對照組、微創(chuàng)治療組、微創(chuàng)+藥物組。各實驗組分別于模型制作成功后6h、12h、18h、24h時實施相關(guān)處理，正常對照組只針刺刺激既不注入血腫也不微創(chuàng)治療，模型對照組進行假性血腫清除，微創(chuàng)治療組實行立體定向微創(chuàng)顱內(nèi)血腫清除術(shù)，微創(chuàng)+藥物組進行微創(chuàng)血腫清除的同時于病灶區(qū)灌注羅格列酮2.5mg（溶于0.5ml的生理鹽水），各組動物在模型制作成功后3天全部處死，處死后稱量不同組別體重相近的家兔病灶周圍腦組織的干濕重并計算腦水含量，采用Western blot檢測各組家兔血腫周圍腦組織PPARγ及其下游基因CD36的表達，采用高效液相色譜（HPLC）測定血腫周圍組織谷氨酸的含量。結(jié)果1.PPARγ及其下游基因CD36的蛋白表達結(jié)果：模型對照組PPARγ及其下游基因CD36表達與微創(chuàng)治療組及微創(chuàng)+藥物組相比，差異有統(tǒng)計學(xué)意義（P＜0.05），在微創(chuàng)+藥物組中表達最多，在微創(chuàng)治療組中表達最少，其中微創(chuàng)治療組和微創(chuàng)+藥物組每組4個時間窗中PPARγ及其下游基因CD36的表達比較，發(fā)現(xiàn)6h、12h、18h、24h時組內(nèi)差異均有統(tǒng)計學(xué)意義（P＜0.05），且在6h較其他3個時間窗表達最少（P＜0.05）。2.谷氨酸、腦組織水含量的結(jié)果：與正常對照組比較，模型對照組、微創(chuàng)治療組及微創(chuàng)+藥物組都明顯高于正常對照組，并且微創(chuàng)+藥物組明顯低于模型對照組，微創(chuàng)治療組較給藥組稍微低于模型對照組，組間差異均具有統(tǒng)計學(xué)意義（P＜0.05）。在模型對照組、微創(chuàng)治療組及微創(chuàng)+藥物組中，在6h的時候結(jié)果是最低的，隨著時間窗的遞進，在24h時達到4個時間窗中最高。在模型對照組、微創(chuàng)治療組及微創(chuàng)+藥物組中任意兩個時間窗都有顯著的差異（P＜0.05）。結(jié)論早期進行立體定向微創(chuàng)血腫清除術(shù)聯(lián)合羅格列酮治療可顯著減輕家兔急性期腦出血灶周圍腦組織的損傷，減少腦組織含水量，減少谷氨酸的產(chǎn)生，其治療機制可能與羅格列酮中過氧化酶活化增生受體γ在激活小膠質(zhì)細胞和巨噬細胞吞噬清除壞死或凋亡細胞和降低應(yīng)激氧化應(yīng)激方面都起著非常重要的作用。
[Abstract]:Objective to investigate the different therapeutic effects of stereotactic minimally invasive hematoma clearance combined with rosiglitazone focal area perfusion in the treatment of intracerebral hematoma by establishing a rabbit model of intracerebral hemorrhage. To provide the experimental basis for selecting the best time window of stereotactic minimally invasive hematoma removal combined with rosiglitazone in the treatment of intracerebral hemorrhage. Methods A total of 84 healthy New Zealand rabbits, weighing 2.8-3.4 kg (male and female), were randomly divided into normal control group and model control group. Minimally invasive treatment group, minimally invasive drug group. Each experimental group was treated at 6 h, 12 h, 18 h and 24 h after the model was successfully made. The normal control group was treated with acupuncture stimulation neither injected into hematoma nor minimally invasive treatment, while the model control group was treated with pseudohematoma clearance. In the minimally invasive treatment group, stereotactic minimally invasive intracerebral hematoma clearance was performed, and rosiglitazone 2.5mg (saline dissolved in 0.5ml) was instilled into the focus area while the minimally invasive drug group was perfused with rosiglitazone 2.5mg. The animals in each group were all killed 3 days after the establishment of the model. After death, the dry and wet weights of the brain tissue around the lesion were measured and the content of brain water was calculated. The expression of PPAR 緯 and its downstream gene CD36 in the brain tissue around the hematoma was detected by Western blot. The content of glutamate in perihematoma tissue was determined by high performance liquid chromatography (HPLC). Results the protein expression of 1.PPAR 緯 and its downstream gene CD36: the expression of PPAR 緯 and its downstream gene CD36 in the model control group was significantly higher than that in the minimally invasive treatment group and the minimally invasive drug group (P < 0. 05). In the minimally invasive treatment group, the expression of PPAR 緯 and its downstream gene CD36 were compared between the minimally invasive treatment group and the minimally invasive drug group in 4 time windows. It was found that there were significant differences between the two groups at 6h, 12h, 18h and 24h (P < 0.05), and the lowest expression was found at 6h (P < 0.05) compared with the other three time windows (P < 0.05). Results: compared with the normal control group, the model control group, the minimally invasive treatment group and the minimally invasive drug group were significantly higher than the normal control group, and the minimally invasive drug group was significantly lower than the model control group. The difference between the two groups was statistically significant (P < 0.05). In the model control group, the minimally invasive treatment group and the minimally invasive drug group, the results were the lowest at 6 h, and reached the highest in 4 time windows at 24 h with the progression of the time window. There were significant differences between the two time windows in the model control group, the minimally invasive treatment group and the minimally invasive drug group (P < 0.05). Conclusion early stereotactic minimally invasive hematoma removal combined with rosiglitazone can significantly reduce brain tissue injury, water content and glutamate production in rabbits with acute cerebral hemorrhage. The therapeutic mechanism may be related to the role of peroxidase activated proliferative receptor 緯 in rosiglitazone in activation of microglia and macrophages in phagocytosis of necrotic or apoptotic cells and in reducing stress oxidative stress.
【學(xué)位授予單位】：貴陽醫(yī)學(xué)院
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號】：R743.34

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1 韓寧;丁素菊;吳濤;朱幼麗;;大鼠腦出血模型中神經(jīng)細胞凋亡與自由基水平的相關(guān)性(英文)[J];Neuroscience Bulletin;2008年06期

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