摘要
背景:脑出血患者常遗留严重的神经功能缺损。目前关于其发病机制的研究日益深入,希望能找到改善预后的有效方法。目的:经脑内血肿腔局部应用神经节苷脂(Ganglioside)GM-1,探讨脑内局部给药能否有减低药量而提高疗效的效果,同时脑内局部用药是否具有局部量效关系。设计:随机对照的实验研究。单位:西安交通大学第二医院神经外科、设备科。对象:实验于2000-08/2001-04在西安交通大学医学院神经生物研究中心完成。选择健康雄性SD大鼠,体质量250～300g,由陕西中医研究院实验动物中心提供。干预:将大鼠随机分为4组:①假手术组(12只):行右侧尾状核穿刺。②模型组(12只):于右侧尾状核注入50μL未抗凝自体血。③局部给药组:分为大、中、小剂量组(每组12只)。制作模型后6h分别按照2mg/kg,0.8mg/kg和0.32mg/kg于脑内血肿腔注入GM-1,液量按2mg/kg计算,不足部分用对照液(即GM1注射液溶剂,按说明书配制)补齐,同时经尾静脉注入相等体积对照液。④全身给药组(12只):制作模型后6h经尾静脉注入GM-12mg/kg,同样体积对照液注入右侧尾状核。上述各组于脑出血后72h处死,测定脑含水量(每组取8只);行组织学检查(每组取4只),并作相对损失神经元计数。主要观察指标:①脑水含量。②组织学观察。③相对损失神经元计数。
BACKGROUND:Patients of cerebral hemorrhage usually suffer from serious defect of nervous function.Researches regarding its pathogenesis gradually go in depth at present,which are for the effective method in the improvement of prognosis. OBJECTIVE:To explore whether intracerebral local medication could reduce dose and improve effectiveness and whether intracerebral local medication has local dose effect relationship through the local application of Ganglioside GM 1 in intracerebral hematoma cavity. DESIGN:A randomized and controlled trail. SETTING:Department of Neurosurgery and Department of Instruments,the Second Hospital,Xi'an Jiaotong University. MATERIALS:Study was performed in the Researching Center of Neurobiology,Faculty of Medicine,Xi'an Jiaotong University from August 2000 to April 2001. Healthy male SD rats with a body mass between 250 g and 300 g were obtained from the experimental animal center of Institute for Traditional Chinese Medicine,Shaanxi Province. INTERVENTIONS:Rats were randomly divided into four groups: ①sham operation group(n=12):Puncture into right caudate nucleus was performed;②model group(n=12):50 μL of autologous blood without anti coagulation was injected into right caudate nucleus;③local medication groups:divided into high dose,middle dose,and low dose subgroups(n=12 of each).2 mg/kg,0.8 mg/kg or 0.32 mg/kg of GM 1 was injected respectively into the intracerebral hematoma cavity in rats of the corresponding subgroups at 6 hours after the establishment of animal model.The quantity of the solution was calculated with 2 mg/kg and the deficient part of the solution was fetched up with control solution(i.e.,the solvent of GM 1 injection solution, confect based on the instructor).Same volume of control solution was injected into caudate vein simultaneously in rats of medication groups;④general medication group(n=12):2 mg/kg of GM 1 was injected into caudate vein at 6 hours after the establishment of the animal model and the control solution of same volume was injected into right caudate nucleus as well. Rats of the above groups were executed at 72 hours after cerebral hemorrhage for the detection of brain water content(8 rats were taken from each group),the examination of histology(4 rats were taken from each group),and the calculation of the comparative counting of neuron loss. MAIN OUTCOME MEASURES:①brain water content;②histological observation;③comparative counting of neuron loss. RESULTS:Brain water content in rats of intracerebral local medication high dose subgroup was(79.77±0.94)%,which was significantly lower than(81.42±0.87)%of general medication group(P=0.02).There was no linear relationship between brain water content and dose in intracerebral local medication groups after linear regression analysis(P=0.001). Comparative counting of neuron loss in rats of intracerebral local medication high dose subgroup was(324.00±3.65),which was significantly lower than(344.00±8.83) of general medication group(P=0.003). Histological observation indicated that survived neurons were significantly more in intracerebral local medication high and middle dose subgroups than low dose subgroup. CONCLUSION:With same dose, intracerebral local application of Ganglioside GM 1 can significantly improve therapeutic effectiveness,which gradually increases with the increase of local medication dose,although there is no linear relationship between dose and effect.
出处
《中国临床康复》
CSCD
2004年第34期7853-7855,F003,共4页
Chinese Journal of Clinical Rehabilitation
基金
国家自然科学基金资助项目(30270481)~~
