实验性大鼠高血压脑动脉瘤模型的建立
发布时间：2019-03-15 17:15
【摘要】： 目的 探讨实验性大鼠高血压脑动脉瘤形成及脑血管早期病理改变与脑动脉瘤形成的关系。 材料和方法 1、实验材料 选用雄性S-D大鼠75只，年龄6—7周，体重200-250克，动物及实验室均由中国医科大学附属盛京医院动物实验中心提供。 2、实验方法 (1)动物分组 将75只SD大鼠随机分进A，B，C三组，A组(实验组)：SD大鼠30只，全部左颈总动脉结扎+经腹正中入路行双肾动脉后支电凝+术后1周1％盐水代替饮用水；B组(高血压组)：SD大鼠30只，经大鼠腹正中入路行双肾动脉后支电凝+术后1周1％盐水喂养；C组(正常对照组)：不处理+自来水喂养 (2)鼠尾动脉血压的测量 所有SD实验大鼠术前1天测量鼠尾动脉压作为基础血压。并分别在手术后2周，6周，10周及处死前测量血压。 (3)大鼠颅内动脉瘤标本的获取 12周后，全部大鼠在全麻下(方法同上)，通过开胸左心室插管至升主动脉处，先用生理盐水30ml经导管灌注，同时剪开腔静脉排放血液，然后用4％多聚甲醛／0.1M磷酸缓冲液(pH7.4)120ml经导管缓慢注入，当灌注固定后将大鼠断颈，开颅取脑，在10—16倍手术显微镜下将Willis环仔细分离取出，再在40倍显微镜下检查Willis环，尤其是右侧的大脑前动脉一嗅动脉(anterior cerebralartery-olfactoryartery，ACA-OA)段的动脉瘤样改变。 (4)动脉瘤标本的光镜观察 10％甲醛固定，酒精梯度脱水，石蜡包埋切片，常规HE染色。 (5)动脉瘤标本的透射电镜检查 将动脉瘤标本浸泡于2.5％戊二醛中预固定24小时，1％四氧化饿再固定，丙酮逐级脱水，Epon812包埋，半薄切片光学定位，超薄切片醋酸铀及构椽酸铅双重染色，超薄切片用JEM-1200EX型透射电镜观察，拍片。 3、统计学方法 用SPSS for Windows10.0作实验组和对照组不同时间点收缩压的t检验，P＜0.01时，差异有显著性意义。 实验结果 1、生存情况 试验组存活28只，高血压组存活29只，正常对照组全部存活。3只死亡大鼠死因不明，不排除为恶性高血压致死。 2、血压变化 实验组和高血压组自第2周起比对照组血压显著升高，以后血压稳步上升。正常对照组血压则保持在正常范围。方差分析结果：A组和B组血压不能认为有差异(P＞0.05)；A，B两组与C组的血压差异有显著性意义(P＜0.01) 3、光镜和电镜观察结果 A组生存的28只大鼠显微镜下共出现10个动脉瘤，均在ACA—OA分叉处。动脉瘤前期6例，早期动脉瘤3例，进展期脑动脉瘤1例，余13例，B组29只和C组15只大鼠在动脉分叉处及主干上均未见动脉瘤样结构改变。 讨论 颅内动脉瘤破裂常表现为自发性蛛网膜下腔出血(SAH)和颅内血肿，致残率和死亡率很高。如果对该病的发病机制有正确的认识并采取及时有效的诊断、干预和治疗，该病的预后将会明显改善。因此探讨动脉瘤的病理形态、演变过程和临床治疗具有重要的意义。由于临床上对动脉瘤无法研究动脉瘤的形成、发展过程，所以建立和研究经济、有效的脑动脉瘤动物模型，揭示其发病机理十分重要。 大鼠脑动脉瘤模型则具有经济、动脉瘤通畅率高(由于动脉搏动快，发生血栓可能性小)，血管不易痉挛等优点，而且较符合人类脑动脉瘤的病理生理改变。 大鼠肾性高血压导致脑动脉瘤的发生率在10％～30％之间，本组脑动脉瘤样改变的发生率为36％(10／28)，其原因可能与试验组无感染，生存率较高，成功诱导高血压有关系。而脑动脉瘤全部是发生在颈总动脉非结扎侧动脉ACA—OA分叉部，，其原因与血流动力学改变和该处动脉壁发生退行性变有关。在高血压的基础上，结扎一侧颈总动脉增加了对侧的脑灌注，在巨大的血流冲击下，轴心血流冲击ACA-OA分叉部导致局部血管壁内弹力膜破坏、内皮细胞受损、血管弹力组织和平滑肌层及动脉瘤壁中的胶原受损，致使动脉瘤形成。 总之，实验性大鼠高血压脑动脉瘤模型是经济、有效的脑动脉瘤动物模型，其成瘤率高且与人类颅内动脉瘤部位及病理生理改变相似，特别在脑微动脉瘤形成、发展过程的方面具有研究价值。 结论 血液动力学压力增高改变结合Willis环一侧过度灌注的脑血流是建立颅内动脉瘤动物模型的基本条件，其引起的内弹力膜与平滑肌的破坏是脑动脉瘤发生的因素之一。
[Abstract]:Purpose To explore the formation of cerebral aneurysms and the early pathological changes of the cerebral vessels and the cerebral artery in experimental rats the close of the formation of the tumor Department. Materials and methods 1,75 male S-D rats,6-7 weeks of age and 200-250 g of body weight were selected for the experimental materials. and the laboratory From China Medical University The animal experiment center of the attached Shengjing Hospital provided.2. The experimental method (1) randomly divided 75 SD rats into groups A, B and C and group A (experimental group). :30 SD rats, total left-neck total artery ligation + 1 week post-operation 1% saline instead of drinking water and group B (hypertension group). ):30 SD rats The double-kidney in the middle of the rat's abdomen Post-arterial electrocoagulation + 1% saline at 1 week post-operation; Group C (normal control group ): Do not process + tap water to feed (2) rat tail artery Measurement of blood pressure all S The pressure of the rat tail artery was measured 1 day before operation. The blood pressure was measured at 2,6,10 and 10 weeks after operation. (3) The rat's intracranial artery After 12 weeks of acquisition of the tumor specimen, all rats were given under general anesthesia (the same method as above), and the left ventricle was inserted into the ascending aorta by opening the left ventricle of the chest, and the blood was discharged through the catheter at the same time by using 30 ml of normal saline, and then the blood was discharged by a 4% paraformaldehyde/ 0.1 M phosphate buffer (pH 7.4). 120 ml was slowly injected through the catheter, and after the perfusion and fixation, the rat's neck was broken, the brain was taken out, the Willis ring was carefully separated and taken out under a 10-16-fold operation microscope, and the Wi-Fi was examined under a 40-fold microscope. The lis ring, especially the right side. anterior cerebral artery ry-olfactoriyart Aneurysm-like changes in the operative, ACA-OA sections. (4) The light microscope of the aneurysm specimens observed 10% formaldehyde fixation, alcohol gradient dehydration, paraffin-embedded sections, and conventional HE staining. (5) Transmission electron microscope examination of aneurysm specimen Aneurysm specimen soaking in 2.5% of glutaraldehyde for pre-fixation for 24 hours,1% of 4-oxidation-hungry and re-fixing, step-by-step dehydration of acetone, embedding of Epon 812, optical positioning of semi-thin sections, and ultra-thin slice acetic acid uranium and lead-acid lead Double staining, ultra-thin sections were observed with the JEM-1200EX type transmission electron microscope, and patted.3. The statistical method SPSS (SPSS) t-test of the systolic blood pressure at different time points in the experimental group and the control group When P is less than 0.01, the difference is significant. Y.Experimental results 1. The survival rate of the test group was 28. The survival of the hypertension group was 29, and the normal control group. all alive.3 dead rats The cause of death is unknown and is not excluded from the death of malignant hypertension. 2. Blood pressure change The blood pressure of the experimental group and the hypertension group increased significantly from the second week to the control group, and the blood pressure of the control group increased steadily. The blood pressure in the normal control group was kept in the normal range. The results of the analysis of variance: The blood pressure of group A and group B could not in the opinion of The difference of blood pressure in group A and group B was significant (P <0.01). 3. A total of 10 aneurysms were observed under the microscope and electron microscope. At the bifurcation of the ACA-OA branch,6 cases in the early stage of the aneurysm,3 cases of the early aneurysm,3 cases of the early aneurysm, There were 1 case of extended cerebral aneurysm,13 of them,29 in group B and 15 in group C, and no change of the structure of the aneurysm was found in the branch of the artery and the trunk. The rupture of the intracranial aneurysm is often shown as the spontaneous subarachnoid hemorrhage (SAH) and the intracranial hematoma, and the residual rate and the mortality rate are high. Effective diagnosis, intervention and treatment can improve the prognosis of the disease. Therefore, it is of great significance to study the pathological form, the evolution process and the clinical treatment of the aneurysm. And the cerebral aneurysm model of the rat has the advantages of economy, and the patency rate of the aneurysm. High (due to the rapid arterial pulse, small possibility of thrombosis), difficult vasospasm and the like, and is more in line with the pathophysiological changes of human brain aneurysms. The incidence of cerebral aneurysms in rats with renal hypertension The incidence of cerebral aneurysm-like changes in this group was 36% (10% ~ 30%). /28), the cause may be no infection with the test group, the survival rate is high, and the hypertension is successfully induced. to be returned to the world on the basis of high blood pressure, the common carotid artery on one side of the ligature increases the cerebral perfusion on the side, and under the great flow of blood flow, the blood flow of the axial center and the ACA-OA bifurcation result in the destruction of the elastic membrane in the local blood vessel wall, and the endothelial cell
【学位授予单位】：中国医科大学
【学位级别】：硕士
【学位授予年份】：2007
【分类号】：R-332
本文编号：2440826
[Abstract]:Purpose To explore the formation of cerebral aneurysms and the early pathological changes of the cerebral vessels and the cerebral artery in experimental rats the close of the formation of the tumor Department. Materials and methods 1,75 male S-D rats,6-7 weeks of age and 200-250 g of body weight were selected for the experimental materials. and the laboratory From China Medical University The animal experiment center of the attached Shengjing Hospital provided.2. The experimental method (1) randomly divided 75 SD rats into groups A, B and C and group A (experimental group). :30 SD rats, total left-neck total artery ligation + 1 week post-operation 1% saline instead of drinking water and group B (hypertension group). ):30 SD rats The double-kidney in the middle of the rat's abdomen Post-arterial electrocoagulation + 1% saline at 1 week post-operation; Group C (normal control group ): Do not process + tap water to feed (2) rat tail artery Measurement of blood pressure all S The pressure of the rat tail artery was measured 1 day before operation. The blood pressure was measured at 2,6,10 and 10 weeks after operation. (3) The rat's intracranial artery After 12 weeks of acquisition of the tumor specimen, all rats were given under general anesthesia (the same method as above), and the left ventricle was inserted into the ascending aorta by opening the left ventricle of the chest, and the blood was discharged through the catheter at the same time by using 30 ml of normal saline, and then the blood was discharged by a 4% paraformaldehyde/ 0.1 M phosphate buffer (pH 7.4). 120 ml was slowly injected through the catheter, and after the perfusion and fixation, the rat's neck was broken, the brain was taken out, the Willis ring was carefully separated and taken out under a 10-16-fold operation microscope, and the Wi-Fi was examined under a 40-fold microscope. The lis ring, especially the right side. anterior cerebral artery ry-olfactoriyart Aneurysm-like changes in the operative, ACA-OA sections. (4) The light microscope of the aneurysm specimens observed 10% formaldehyde fixation, alcohol gradient dehydration, paraffin-embedded sections, and conventional HE staining. (5) Transmission electron microscope examination of aneurysm specimen Aneurysm specimen soaking in 2.5% of glutaraldehyde for pre-fixation for 24 hours,1% of 4-oxidation-hungry and re-fixing, step-by-step dehydration of acetone, embedding of Epon 812, optical positioning of semi-thin sections, and ultra-thin slice acetic acid uranium and lead-acid lead Double staining, ultra-thin sections were observed with the JEM-1200EX type transmission electron microscope, and patted.3. The statistical method SPSS (SPSS) t-test of the systolic blood pressure at different time points in the experimental group and the control group When P is less than 0.01, the difference is significant. Y.Experimental results 1. The survival rate of the test group was 28. The survival of the hypertension group was 29, and the normal control group. all alive.3 dead rats The cause of death is unknown and is not excluded from the death of malignant hypertension. 2. Blood pressure change The blood pressure of the experimental group and the hypertension group increased significantly from the second week to the control group, and the blood pressure of the control group increased steadily. The blood pressure in the normal control group was kept in the normal range. The results of the analysis of variance: The blood pressure of group A and group B could not in the opinion of The difference of blood pressure in group A and group B was significant (P <0.01). 3. A total of 10 aneurysms were observed under the microscope and electron microscope. At the bifurcation of the ACA-OA branch,6 cases in the early stage of the aneurysm,3 cases of the early aneurysm,3 cases of the early aneurysm, There were 1 case of extended cerebral aneurysm,13 of them,29 in group B and 15 in group C, and no change of the structure of the aneurysm was found in the branch of the artery and the trunk. The rupture of the intracranial aneurysm is often shown as the spontaneous subarachnoid hemorrhage (SAH) and the intracranial hematoma, and the residual rate and the mortality rate are high. Effective diagnosis, intervention and treatment can improve the prognosis of the disease. Therefore, it is of great significance to study the pathological form, the evolution process and the clinical treatment of the aneurysm. And the cerebral aneurysm model of the rat has the advantages of economy, and the patency rate of the aneurysm. High (due to the rapid arterial pulse, small possibility of thrombosis), difficult vasospasm and the like, and is more in line with the pathophysiological changes of human brain aneurysms. The incidence of cerebral aneurysms in rats with renal hypertension The incidence of cerebral aneurysm-like changes in this group was 36% (10% ~ 30%). /28), the cause may be no infection with the test group, the survival rate is high, and the hypertension is successfully induced. to be returned to the world on the basis of high blood pressure, the common carotid artery on one side of the ligature increases the cerebral perfusion on the side, and under the great flow of blood flow, the blood flow of the axial center and the ACA-OA bifurcation result in the destruction of the elastic membrane in the local blood vessel wall, and the endothelial cell
【学位授予单位】：中国医科大学
【学位级别】：硕士
【学位授予年份】：2007
【分类号】：R-332
【参考文献】
相关期刊论文 前1条
1 郭予大;韩天旺;郭付有;游潮;;大鼠双侧肾动脉后支结扎术制作肾性高血压模型[J];中华实验外科杂志;2006年01期
本文编号：2440826
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