中文摘要
中文摘要
随着世界人口老龄化，脑出血(intracerebral hemorrhage，ICH)的发病率逐年升高，引起了世界各国人们的关注[1]。脑血管病是危害人类健康的主要疾病，具有发病率、死亡率、致残率高三大特征[2]，在我国是死亡及致残的重要原因。据有关统计估计，我国脑卒中发病l50万／年，75％致残，其中40％重残[3]。目前无论是脱水降颅压、营养神经、调节血压等内科治疗方法，还是开颅手术清除血肿、开瓣减压、脑室引流等外科方法都不能有效地降低致死率和致残率。因此对脑出血的病理机制进行研究有着重要的意义[4]。
目前对脑出血损伤机理的研究大多集中在对脑出血中血肿、水肿，对于脑出血后抑制性氨基酸及其受体和转运体变化方面的研究还很少见到报道。GABA A 受体（GABA A R）是配体门控离子通道超家族成员之一，主要负责神经突触间的抑制性信号传递[5]。GABA转运体(GABA transporter，GAT)位于神经元和胶质细胞上，能够快速摄取突触间隙和细胞外液的GABA，以终止GABA对突触后膜受体的作用，结束GABA的突触传递过程[6]。
在人类，纹状体主要功能为自主运动的控制。同时它还参与记忆、情感和奖励学习等高级认知功能。纹状体的病变可导致多种运动和认知障碍，目前也是研究的热点。但是也没有见到纹状体损伤与脑出
血后的神经损伤和运动障碍关系的报道。
奔走相告本实验室前期研究成果发现：（1）实验性脑出血大鼠海马内Glu、GABA含量发生相应变化，可能是由于其代谢酶GAD、GABA-T活性的变化而引起的；（2）通过免疫组化检测炎症因子肿瘤坏死因子（TNF-α）和IL-1β的表达变化，发现在脑出血大鼠脑组织中TNF-α和IL-1β都有大量表达[7]。
研究方法及目的：本实验采用给试验大鼠尾状核注射胶原酶+肝素钠复制脑出血动物模型，用GABA A R的激动剂（GABA）和拮抗剂（bicuculline）作用于脑出血模型大鼠，分假手术、ICH模型组、GABA组和荷包牡丹碱（bicuculline）组四组，采用HE染色对大鼠脑内纹状体部位神经细胞的形态变化、用高效液相色谱仪（high performance liquid chromatography，HPLC）对神经递质兴奋性氨基酸（excitability amino acid，EAA）/抑制性氨基酸（inhibitory amino acid，IAA）的
GABAA受体的激动剂和拮抗剂对实验性脑出血大鼠脑损伤的影响学生祛痘>华县地震
动态平衡、用免疫组化法对GABA A Rα1与GAT-1变化进行研究，以期待对GABA A R通道在脑出血中的作用、对GABA A R和GAT与脑出血损伤的关系、对脑出血神经损伤机制、对纹状体与脑出血后神经损伤和运动障碍的关系、对“兴奋毒性损伤学说”进行探讨、论证和完善，为脑出血的治疗提供依据。
研究结果：
1. 模型组和bicuculline组中大鼠大脑出血情况明显加重，其中bicuculline 组大鼠脑组织出现大面积坏死；而GABA组大鼠与模型组及bicuculline组相比较脑出血情况明显改善，HE染色后观察神经元细胞及纹状体细胞的损伤都有显著性缓解。
jitapu2. 用HPLC检测各组大鼠脑组织主要氨基酸类神经递质含量后发现，模型组和bicuculline组脑组织中谷氨酸含量比假手术组显著升高；GABA组谷氨酸含量与模型组和bicuculline组比较有显著性下降，GABA含量有显著性升高。
3. 用免疫组化方法检测各组大鼠脑组织GABA A Rα1与GAT-1的变化发现，bicuculline组中GABA A Rα1阳性细胞数与假手术组比较明显减少，而GAT-1却明显增加；GABA组中GABA A Rα1阳性细胞数与假手术组比较有所增加，而GAT-1变化不明显。
结论本试验结果发现脑出血后血肿形成后的占位效应，导致局部脑组织缺血、缺氧，进而导致细胞膜通透性改变，Ca2+大量流入细胞内，兴奋性氨基酸谷氨酸增加，GABA A R表达减少，GAT-1表达增加，EAA/IAA平衡被破坏，加重神经毒性损伤，神经细胞及纹状体受损。而GABA能增加脑组织中抑制性氨基酸含量，增加GABA A R的表达，激活Cl-通道，Cl-内流，使细胞膜超极化，产生抑制性突触后电位，抑制突触后神经元兴奋性，保护脑组织神经细胞。
关键词：脑出血、HPLC、GABA、纹状体、GABA A R、GAT
早穿皮袄午穿纱
ABSTRACT
ABSTRACT
With the aging of world’s population, the incidence of intracerebral hemorrhage is increasing, this phenomenon arou people’s attentions. Cerebrovascular dia is the major dias against human health and which has three major characteristics: the high rate of morbidity, the high rate of mortality, the high rate of deformity. It is an important cau of disability in our country. According to the relevant estimation, stroke incidence in our country is about l50 million / year, 75% disability, of which 40% of verely disabled. At prent, no matter what kind of internal medicine cure method such as reducing intracranial pressure by dehydration, reinforcing nutrition supply to nerve, regulating blood pressure, or surgery method such as craniotomy to clean up hematoma, all of them will not reduce mortality and deformity effectively. So it has an important significance on the rearch of the pathology mechanism of cerebral hemorrhage.
养老保险缴费查询At prent, the rearch on the damage mechanism of cerebral hemorrhage are mostly focud on hematoma, dropsy in cerebral hemorrhage, but the rearch on the changes of inhibitory amino acids，their receptors and transporters after cerebral hemorrhage, are rarely reported. GABA A rece
ptor（GABA A R）is a member of superfamily in ligand-gated ion channels，which is mainly responsible for the inhibitory signal’s transport among nerve synaps. GABA transporter（GAT）locates in the neurons and glial cells，it could incept GABA of synap gap and extracellular fluid rapidly to stop the effect on the postsynaptic membrane receptor and finish the transporting process among synaps.
In human, the striatum’s mainly function is controlling independence action. It also participates in the advanced functions such as recollection, emotion and encouraging study. The pathological changes of striatum will lead to many kinds of sport and cognization problem, it is also a hotspot in rearch. But the rearch on the relationship between the damage of striatum，the damage of nerve after cerebral hemorrhage and dyskinesia are not reported.boosted
GABAA受体的激动剂和拮抗剂对实验性脑出血大鼠脑损伤的影响
Rearch methods and goals: In this experiment, the collagen enzyme + heparin sodium were injected into caudate nucleus to duplicate cerebral hemorrhage model in the rats, and the rats were treated with the agonist (GABA ) and antagonist (bicuculline ) of GABA A receptor .The experiment rats were divided into the sham group, the ICH group, the GABA group and the bicuculline group. Th
e morphological changes of the nerve cell of corpora striata in the rats were rearched by HE. The dynamic equilibrium of the neurotransmitters excitability amino acid (EAA ) / inhibitory amino acid (IAA ) was measured by high performance liquid chromatography (HPLC).
Results:
感恩节英语
1. The cerebral hemorrhage in rats is obviously aggravated in model group and bicuculline group, the large necrosis area among them was appeared in the rat’s brain organization of bicuculline group. Compared with one in the bicuculline group, the cerebral hemorrhage was obviously improved in the rat of GABA and model groups, and the results were aslo confirmed by the method of HE.
2. The concentration of neurotransmitters in the groups was detected by HPLC. Compared with ones in the sham group, the contents of glutaminic acid in model group and in bicuculline group were obviously incread . Compared with ones in the bicuculline group, the contents of glutaminic acid in GABA group and in model group were significantly decread, and the concentration of GABA was remarkablely incread.
3. The changes of GABA A Rα1and GAT-1 were detected by the immunohisto- chemical method. Co
mpared with ones in the sham group, the positive cell numbers of GABA A Rα1 were obviously declined and ones of GAT-1 were notably incread in bicuculline group. But compared with ones in the sham group, the positive cell numbers of GABA A Rα1 was incread and ones of GAT-1 were not change in GABA group.
Conclusions:Taking the location effect was found after the hematoma was formed caud by cerebral hemorrhage, and then the permeability of cell membrane was changed. Ca2+ was flowed into cell in a large amount, and the excitability amino
