立体定向微创颅内血肿清除技术结合罗格列酮病灶区灌注治疗脑出血的时间窗研究
发布时间：2018-10-19 16:09
【摘要】：目的通过建立家兔脑出血的模型，，探讨立体定向微创血肿清除术在不同时间段清除颅内血肿结合罗格列酮病灶区灌注治疗颅内血肿的不同疗效，为临床选择立体定向微创血肿清除术结合罗格列酮治疗脑出血的最佳治疗时间窗提供实验依据。方法共选取健康新西兰大白兔84只，体重为2.8-3.4公斤（雌雄不分），通过立体定向技术构建自体动脉血脑出血模型，模型构建成功后随机分成正常对照组、模型对照组、微创治疗组、微创+药物组。各实验组分别于模型制作成功后6h、12h、18h、24h时实施相关处理，正常对照组只针刺刺激既不注入血肿也不微创治疗，模型对照组进行假性血肿清除，微创治疗组实行立体定向微创颅内血肿清除术，微创+药物组进行微创血肿清除的同时于病灶区灌注罗格列酮2.5mg（溶于0.5ml的生理盐水），各组动物在模型制作成功后3天全部处死，处死后称量不同组别体重相近的家兔病灶周围脑组织的干湿重并计算脑水含量，采用Western blot检测各组家兔血肿周围脑组织PPARγ及其下游基因CD36的表达，采用高效液相色谱（HPLC）测定血肿周围组织谷氨酸的含量。结果1.PPARγ及其下游基因CD36的蛋白表达结果：模型对照组PPARγ及其下游基因CD36表达与微创治疗组及微创+药物组相比，差异有统计学意义（P＜0.05），在微创+药物组中表达最多，在微创治疗组中表达最少，其中微创治疗组和微创+药物组每组4个时间窗中PPARγ及其下游基因CD36的表达比较，发现6h、12h、18h、24h时组内差异均有统计学意义（P＜0.05），且在6h较其他3个时间窗表达最少（P＜0.05）。2.谷氨酸、脑组织水含量的结果：与正常对照组比较，模型对照组、微创治疗组及微创+药物组都明显高于正常对照组，并且微创+药物组明显低于模型对照组，微创治疗组较给药组稍微低于模型对照组，组间差异均具有统计学意义（P＜0.05）。在模型对照组、微创治疗组及微创+药物组中，在6h的时候结果是最低的，随着时间窗的递进，在24h时达到4个时间窗中最高。在模型对照组、微创治疗组及微创+药物组中任意两个时间窗都有显著的差异（P＜0.05）。结论早期进行立体定向微创血肿清除术联合罗格列酮治疗可显著减轻家兔急性期脑出血灶周围脑组织的损伤，减少脑组织含水量，减少谷氨酸的产生，其治疗机制可能与罗格列酮中过氧化酶活化增生受体γ在激活小胶质细胞和巨噬细胞吞噬清除坏死或凋亡细胞和降低应激氧化应激方面都起着非常重要的作用。
[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 纬 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 纬 and its downstream gene CD36: the expression of PPAR 纬 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 纬 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 纬 in rosiglitazone in activation of microglia and macrophages in phagocytosis of necrotic or apoptotic cells and in reducing stress oxidative stress.
【学位授予单位】：贵阳医学院
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R743.34
本文编号：2281643
[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 纬 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 纬 and its downstream gene CD36: the expression of PPAR 纬 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 纬 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 纬 in rosiglitazone in activation of microglia and macrophages in phagocytosis of necrotic or apoptotic cells and in reducing stress oxidative stress.
【学位授予单位】：贵阳医学院
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R743.34
【参考文献】
相关期刊论文 前1条
1 韩宁;丁素菊;吴涛;朱幼丽;;大鼠脑出血模型中神经细胞凋亡与自由基水平的相关性(英文)[J];Neuroscience Bulletin;2008年06期
本文编号：2281643
本文链接：https://www.wllwen.com/yixuelunwen/shenjingyixue/2281643.html
最近更新
教材专著
