脑积水大鼠动物模型的建立及分析

发布时间：2018-03-05 07:43

本文选题：脑出血　切入点：动物模型　出处：《福建医科大学》2011年硕士论文　论文类型：学位论文

【摘要】：背景和目的: 脑积水是脑出血后常见并发症之一,具有很高的发病率。据统计,国外50%的自发性脑出血合并有脑室内出血,其中35%会进一步发展成为脑出血后脑积水,并进一步导致脑实质的继发性损害,是病情加重、预后不良甚至死亡的重要原因。迄今为止,由于对脑出血后脑积水的发生机制尚不完全清楚,因而难以在出血后做好早期防治。脑积水的具体发生机制尚未阐明,值得研究。为此,本实验以多种方式建立了实验性大鼠脑积水模型,并给予对比分析。方法: (1)50只幼年和50只成年SD雄性大鼠随机分为14组,4组生理盐水对照组( n=20)、4组空白对照组(n=20)、2组侧脑室注血组( n=20)、2组侧脑室注射灭菌生理盐水高岭土混悬液组( n=20 )、2组枕大池注射灭菌生理盐水高岭土混悬液组( n=20 )。 (2)采用二次注射法注射130 ul非抗凝自体尾静脉血建立侧脑室注血组;侧脑室注射2%灭菌生理盐水高岭土混悬液同上法注入30 ul;生理盐水对照组同上法注入30 ul生理盐水;空白对照组28 d组不处理,同一环境喂养28 d。 (3)以28 d MRI扫描前囟后0.4 mm冠状面侧脑室宽度评价脑积水发生情况并测量该平面侧脑室侧室指数(侧室面积/脑片面积×100),比较大鼠脑积水发生情况,并行组织病理切片观察脑组织病理变化。 (4) 28 d时随机取侧脑室注血组、侧脑室注射灭菌生理盐水高岭土混悬液组、生理盐水对照组、枕大池注射灭菌生理盐水高岭土混悬液组及空白对照组4只大鼠作Morris水迷宫检测、观察对比行为学变化。结果: (1)生理盐水对照组及正常对照组无脑积水发生;侧脑室注血组脑积水发生率(60%)较侧脑室注射灭菌生理盐水高岭土混悬液组(90%)低(P 0. 05);侧脑室注射灭菌生理盐水高岭土混悬液组(90%)较枕大池注射灭菌生理盐水高岭土混悬液组(50%)脑积水发生率高(P 0. 05);幼年组较成年组脑积水发生率无明显差异(P 0. 05),但脑积水程度较重。 (2)侧脑室注血组大鼠前囟后0.4 mm冠状面侧脑室侧室指数值均值4.79,侧脑室注射灭菌高岭土生理盐水混悬液组均值4.85,枕大池注射灭菌高岭土生理盐水混悬液组均值4.21,生理盐水对照组均值1.09,空白对照组均值1.04。 (3)侧脑室注血组时间逃避潜伏期均值13.58s,侧脑室灭菌生理盐水高岭土混悬液组均值13.03 s,及枕大池注射灭菌生理盐水高岭土混悬液组均值11.32 s均长于生理盐水对照组9.11 s,而搜索平台策略得分均小于生理盐水对照组。 (4)病理学结果:术后4w,中度脑积水大鼠出现部分胼胝体断裂,脉络丛萎缩、室管膜点片状缺失,脑室壁含铁血黄素沉积,大量脑组织细胞增生;而重度脑积水大鼠可见以上病变进一步加重,室周脑组织细胞增生,血管受压、减少,出现泡沫状细胞,室管膜细胞数量减少,纤毛脱落,甚至双侧侧脑室融合。高岭土注射组和自体血注射组大鼠发生同级别脑积水者,脑组织病理学变化呈一致性改变。而对照组无明显变化。结论: 1.本课题所建立的大鼠脑积水模型符合人类脑积水临床特征; 2.本实验采用的二次穿刺采血侧脑室注血法、侧脑室注射高岭土混悬液法及枕大池注射高岭土混悬液法均可以制备脑积水动物模型,三者在脑积水病理组织学相似但以侧脑室注射高岭土混悬液法模型最简便而成功率最高; 3.不同年龄大鼠脑积水模型可分别模拟临床儿童及成人脑积水特征;
[Abstract]:Background and purpose:
Hydrocephalus is one of the common complications after cerebral hemorrhage, have a high incidence rate. According to statistics, 50% of spontaneous cerebral hemorrhage combined with foreign intraventricular hemorrhage, 35% of which will be the further development of hydrocephalus after cerebral hemorrhage, and further lead to brain secondary damage, disease exacerbations, poor prognosis and death reasons so far, the mechanism of hydrocephalus after cerebral hemorrhage is not completely understood, it is difficult to do early prevention and treatment of hemorrhage. The specific pathogenesis of hydrocephalus has not been elucidated, worthy of study. Therefore, this experiment in a variety of ways to establish the experimental rat model of hydrocephalus, and give the comparative analysis.
Method:
(1) 50 juvenile and 50 adult male SD rats were randomly divided into 14 groups, 4 groups of saline control group (n=20), 4 groups of blank control group (n=20), the 2 group received intracerebroventricular injection of blood group (n=20), 2 groups of intracerebroventricular injection of sterile saline group (kaolin suspension n=20), 2 groups of intracisternal injection of sterile saline kaolin suspension group (n=20).
(2) the two injection 130 UL non anticoagulant autologous blood to establish lateral ventricle injection of blood group; intracerebroventricular injection of 2% saline kaolin suspension above method with 30 UL of saline control group; the same method with 30 UL saline; control group 28 d group treated with a fed for 28 d.
(3) 28 d MRI 0.4 mm after scanning anterior lateral ventricle on the coronal width evaluation of hydrocephalus and measure the level of lateral ventricle ventricular index (ventricular area / brain slice area X 100), rat hydrocephalus, parallel pathological change of brain tissue pathological observation.
(4) 28 d randomly intracerebroventricular injection of blood group, intracerebroventricular injection of sterile saline kaolin suspension group, saline control group, intracisternal injection of sterile saline kaolin suspension group and blank control group, 4 rats of the Morris water maze test, observed behavioral changes.
Result:
(1) the normal saline control group and normal control group without the incidence of hydrocephalus; the incidence of intraventricular injection of blood group hydrocephalus (60%) than the intracerebroventricular injection of sterile saline kaolin suspension group (90%) and low (P 0.05); intracerebroventricular injection of sterile saline kaolin suspension group (90%) than intracisternal injection of sterile saline kaolin suspension group (50%) had high incidence of hydrocephalus (P 0.05); juvenile group than the adult group had no significant difference in the incidence of hydrocephalus (P 0.05), but the degree of hydrocephalus is heavy.
(2) intracerebroventricular injection of blood group rats after 0.4 mm coronal anterior lateral ventricle ventricular index mean value 4.79, intracerebroventricular injection of sterile saline kaolin suspension group mean 4.85, intracisternal injection of sterile saline kaolin suspension group mean 4.21, saline control group and blank control group average of 1.09. The mean of 1.04.
(3) intracerebroventricular injection of blood group 13.58s the mean escape latency time, intracerebroventricular sterilized saline kaolin suspension group average of 13.03 s, and cisterna magna injection of sterile saline kaolin suspension group mean 11.32 s were longer than those of the saline control group 9.11 s, while the search platform strategy scores were less than the saline control group.
(4) pathological results: postoperative 4W, moderate hydrocephalus rats part of corpus callosum atrophy fracture, choroid plexus, ependyma patchy absence, ventricular wall hemosiderin deposition, a large number of brain cell hyperplasia; and severe hydrocephalus rats showed more lesions aggravating, periventricular brain cell hyperplasia, vascular compression, reduction, bubble shaped cells, ependymal cells, reduce the number of cilia, and bilateral lateral fusion. The occurrence of hydrocephalus in kaolin injection group and autologous blood injection group rats, the pathological changes of brain tissue showed consistent change. While the control group had no obvious change.
Conclusion:
1. the rat model of hydrocephalus established in this study accords with the clinical characteristics of human hydrocephalus.
The two ventricle puncture blood injection by 2. in this experiment, intracerebroventricular injection of kaolin suspension method and cisterna magna injection of kaolin suspension method can prepare hydrocephalus animal model, three were similar but with intracerebroventricular injection of kaolin suspension model is the most simple and the highest success rate in the brain water;
3. the hydrocephalus model of different age rats can simulate the characteristics of hydrocephalus in children and adults, respectively.

【学位授予单位】：福建医科大学
【学位级别】：硕士
【学位授予年份】：2011
【分类号】：R742.7;R-332

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