Ⅲ型胶原蛋白在大鼠实验性囊性动脉瘤中的表达

目的　探讨Ⅲ型胶原蛋白在大鼠实验性囊性动脉瘤生长塑形过程中的作用。方法　通过显微手术方法破坏大鼠颈动脉分叉部位的内膜和内弹力层诱导囊性动脉瘤 ,在结扎及未结扎对侧颈动脉的情况下 ,观察 4～ 5个月 ,在长、宽、高三个径线上测量动脉瘤的大小。通过免疫组化方法 ,研究Ⅲ型胶原蛋白在正常动脉及动脉瘤壁上的表达。结果　破坏大鼠颈动脉分叉部位的内膜和内弹力层可诱导出囊性动脉瘤 ,在长期血流应力作用下 ,动脉瘤逐渐增大生长塑形 ,并且结扎对侧颈总动脉增加同侧血流冲击 ,可使动脉瘤生长更加明显。在正常动脉壁中膜平滑肌细胞周围有Ⅲ型胶原蛋白的明显表达 ,而在动脉瘤壁上其表达减少 ,并且随着动脉瘤生长塑形其表达进一步减少。结论　囊性动脉瘤在长期血流应力作用下 ,有Ⅲ型胶原蛋白的降解 ,使动脉壁力学性能下降 ,无法抗衡血流应力作用而逐渐生长塑形。     

弹力蛋白酶诱发犬分叉部囊状动脉瘤模型的研究

目的建立犬分叉部囊状动脉瘤模型并研究其形成原因.方法将犬分为3组,将ElastaseI型弹力蛋白酶注入右侧颈总动脉内和(或)结扎右侧颈总动脉,建立分叉部囊状动脉瘤模型,研究动脉瘤的形成过程,1个月内对动脉瘤模型进行复查,并行病理学检查.结果病理和血管造影证实:经酶处理 结扎右侧颈动脉的成瘤率100%,没有结扎而经酶处理过的动脉段没有形成动脉瘤模型,在1个月内弹力板结构有破坏.而单纯结扎动脉组成瘤率为42.8%.结论弹力酶诱发犬分叉部囊状动脉瘤模型重复性好,模型稳定,血流动力学改变是其形成的主要原因,动脉瘤具有良好的形态和病理特征,是比较理想的动脉瘤模型.     

烟雾病与颅内动脉瘤的实验研究

目的 探讨烟雾型与颅内动脉瘤之间的关系。方法 用颈局部注射马血清方法建立烟雾病合并颅内动脉瘤的实验动物模型。结果 颈动脉受免疫复合物损伤后,内弹力层变性,迂曲、断裂,中膜平滑肌细胞沿弹力纤维断裂处向内膜伸入增生,致管腔狭窄或闭塞。脑组织长期缺血,小血管代偿性增生形成异网,同时,颅内动脉壁受免疫复合物损伤后,局部弹力纤维变性,断裂,在侧支血流冲击下向外突出,形成动脉瘤。本实验１０只动物中４只产生５个     

肾血管性高血压大鼠脑动脉瘤模型的建立及发生机制初步探讨

目的 :探讨采用易卒中型肾血管性高血压大鼠建立脑动脉瘤模型。方法 :建立大鼠肾血管性高血压模型 ,再电凝切断左侧颈总动脉 ,然后用光镜和电镜观察右侧大脑前动脉和嗅动脉分叉处及附近的组织学改变。结果 :实验组在 2 0 /2 3只大鼠中可见瘤前、早期及进展期的动脉瘤改变 ,与人类囊状动脉瘤的病理改变相似。结论 :结扎一侧颈总动脉造成血流动力学改变的易卒中型肾血管性高血压大鼠可以作为较理想的脑动脉瘤模型。     

兔颈总动脉侧壁型动脉瘤模型的建立

目的 建立类似人颅内动脉瘤特点的兔颈总动脉侧壁型动脉瘤模型.方法 切取兔左颈总动脉约8mm,经弹性蛋白酶和胶原酶处理后,采用端侧吻合法将其吻合到右颈总动脉,建立侧壁型动脉瘤20只.术后分别行彩色多普勒检查、DSA和动脉瘤壁病理检查.结果 本组建立兔颈部囊状动脉瘤模型20只,术后健康成活18只,动脉瘤自发破裂导致死亡2只.DSA显示:动脉瘤与载瘤动脉通畅16只,动脉瘤腔自发性完全闭塞2只;造模成功率为80％.彩色多普勒发现:动脉瘤模型建立后即刻平均直径为(2.57±0.20) mm,2周后平均直径为(3.14±0.20) mm,两者差异有统计学意义(P＜0.05);且载瘤动脉血流速度较动脉瘤内血流速度快.病理检查显示:动脉瘤模型的动脉壁内弹力层和中弹力层基本消失.结论 经弹性蛋白酶和胶原酶处理的兔颈总动脉侧壁型动脉瘤模型,在形态结构、组织结构、自然发展史及血流动力学特点上与人颅内动脉瘤相似,是模拟人颅内动脉瘤的最佳模型之一.     

动脉结扎法诱导大鼠颅内动脉瘤模型的实验研究

目的 运用动脉结扎法诱导大鼠产生颅内动脉瘤，建立一种真实可信的疾病模型。方法 选用S—D大鼠(体重200—300g)40只，实验组30只大鼠同时结扎左侧颈总动脉和双侧肾动脉后支；对照组10只大鼠未给予手术处理。实验组手术一周后，两组动物均以1％盐水替代饮水喂养3个月。取双侧大脑前动脉—眼动脉(ACA-OA)分叉处组织在光镜下进行病理学检查。结果 实验组23只大鼠共发现5个早期动脉瘤改变，其中4个在动脉结扎对侧(右侧)，1个在动脉结扎同侧(左侧)；对照组双侧均未见动脉瘤样改变。结论 该方法诱导的动脉瘤位于颅内，且发病部位、形态与病理改变均与临床颅内动脉瘤十分相似。因此，该方法建立的颅内动脉瘤模型是研究该病发病机理、影响因素及探索药物或基因治疗的理想选择。     

前循环缺血性卒中老年患者颈动脉斑块及其稳定性与血流壁切应力的关系

目的通过探讨前循环缺血性卒中老年患者颈总动脉分叉处血流壁切应力的水平分析其在颈动脉斑块形成过程中的影响。方法本研究选择前循环缺血性卒中老年患者,应用经皮血管彩超测量颈动脉斑块及其稳定性以及对研究对象测量患侧颈动脉血流速度、血管内径和血液粘滞度,通过公式计算血流壁切应力。结果无斑块组和有斑块组之间、高回声和低回声斑块组之间血流壁切应力均有显著性差异(P<0．01)。结论血流壁低切应力促进颈动脉斑块、尤其是不稳定斑块的形成。     

犬囊状动脉瘤微弹簧圈栓塞治疗前后的超声研究

目的探讨囊状动脉瘤模型的声像图和血流动力学特征以及超声对其血管内栓塞效果的评价。方法利用用显微外科技术于犬颈总动脉制成三种类似于人类的囊状动脉瘤模型，其中侧壁型12例、分叉型4例、末端型6例。术后7～14d彩超观察瘤腔、载瘤动脉及瘤体内血流动力学改变。栓塞后再行彩超检查观察其疗效，并与MRA、DSA及病理检查结果对比。结果三种类型动脉瘤均有相似的血流模式，瘤腔内血流分为三个血流区：1)沿远侧瘤壁进入的流人区；2)沿近侧瘤壁出去的流出区和3)中心缓慢涡流区。流人区峰速高于流出区。②侧壁型动脉瘤内血流速较慢，易形成部分性血栓，而分叉型和末端型动脉瘤内血流速高。③血管内治疗后，血流显示19例动脉瘤腔闭塞，2例瘤颈部有残腔，1例弹簧圈略脱出瘤颈导致载瘤动脉狭窄。④超声结果与MRA、DSA及病理结果完全一致。结论①各型动脉瘤模型有相似的血流模式。②侧壁型动脉瘤顶部易形成部分血栓。③双功超声能观察载瘤动脉及瘤体内血流动力学改变，可作为动脉瘤及栓塞治疗效果无创评价的方法之一。     

实验性肾性高血压大鼠脑动脉瘤模型的建立及发生机制探讨

目的 探讨高血压大鼠脑血管早期病理改变与脑微动脉瘤形成的关系。方法 建立肾性高血压大鼠模型,应用光镜及电镜观察脑血管组织学改变。结果 实验组发现2个肉眼可见的动脉瘤及10个镜下早期动脉瘤。动脉分叉部内膜垫的变化与动脉瘤的病理改变程度有密切关系,动脉瘤形成早期即有内皮细胞损伤。结论 持续高血压引起的内弹力膜与平滑肌的破坏导致了动脉瘤的发生。     

醋酸纤维素聚合物栓塞实验性宽颈动脉瘤的组织学研究

目的观察实验性宽颈动脉瘤被非黏附性液体栓塞剂醋酸纤维素聚合物(CAP)栓塞后的组织学变化。方法犬3只,将颈外动脉和股深动脉结扎建立动脉残端性宽颈动脉瘤模型,随即向动脉瘤腔内注射CAP(注射时用血管夹夹闭动脉瘤颈)。3周后取动脉瘤标本做电镜检查。结果3只动物共制作12个动脉瘤,7个用CAP栓塞。扫描电镜显示瘤体内的CAP团块与动脉瘤内膜紧密贴合,有4个动脉瘤的瘤颈被较完整的新生内皮细胞覆盖。透射电镜显示瘤壁存在轻度炎症,瘤腔被CAP及纤维组织充填。结论宽颈动脉瘤被CAP栓塞后能够达到组织学上表现为瘤颈内皮化和瘤腔纤维化的解剖愈合。     

Expressions of PDGF-B and collagen type III in the remodeling of experimental saccular aneurysm in rats

The essential etiologic factors of intracranial berry aneurysm may be the hemodynamic stress on the arterial wall. Vascular remodeling triggered by abnormal hemodynamic stress on the blood vessels may play an important role in the formation, development and rupture of intracranial aneurysms. However, the specific causative mechanisms associated with this remain elusive. In this study, we look for the possible mechanism of platelet-derived growth factor B (PDGF-B) on the pathogenesis of saccular aneurysms in rats. Direct microsurgical destruction of the arterial intima and internal elastic lamina at the bifurcation of the carotid artery was performed in 30 rats to induce saccular aneurysms and the contralateral carotid arteries were ligated in half of them. After 4-5 months, the size of the aneurysms was determined. The expressions of PDGF-B and collagen type III on the walls of the normal carotid arteries and the saccular aneurysms were determined by in situ hybridization and immunohistochemistry. Saccular aneurysms could be induced immediately by destroying the intima and internal elastic lamina at the bifurcation of the carotid artery in rats. Saccular aneurysms grew significantly due to the hemodynamic stress in 4-5 months, and much bigger after the ligation of the contralateral carotid artery which enhanced the hemodynamic stress. There was no PDGF-B expression on the walls of the normal carotid arteries in rats, but it was expressed on the aneurysmal walls and more distinctly with the growth of the saccular aneurysms. However, there was collagen type III expression on the media of the normal carotid artery, but its expression decreased on the aneurysmal walls and further reduced with the growth of the saccular aneurysms. So, PDGF-B may induce the expression of MMP for the degradation of collagen type III on the wall of the saccular aneurysms. This may be one of the important mechanisms on the pathogenesis of the saccular aneurysm.     

An acute experimental model of saccular aneurysms in the rat

A new and reproducible saccular aneurysm model has been developed at the bifurcation of the common carotid artery in rats. The details of the experimental methods and results are described. It is strongly suggested that the internal elastic lamina is a critical layer in saccular aneurysm formation, because an experimental saccular aneurysm can be produced immediately by transluminally damaging the inside of the arterial wall at the bifurcation of the common carotid artery. This saccular aneurysm model has several advantages: (i) it can be induced quickly and the success rate approaches 100% in rats; (ii) this technique can produce satisfactory experimental saccular aneurysms for other aneurysm studies, and in the future it will also be possible to use this technique to produce experimental saccular aneurysms in cerebral arteries of large animals.     

An acute experimental model of saccular aneurysms in the rat

A new and reproducible saccular aneurysm model has been developed at the bifurcation of the common carotid artery in rats. The details of the experimental methods and results are described. It is strongly suggested that the internal elastic lamina is a critical layer in saccular aneurysm formation, because an experimental saccular aneurysm can be produced immediately by transluminally damaging the inside of the arterial wall at the bifurcation of the common carotid artery. This saccular aneurysm model has several advantages: (i) it can be induced quickly and the success rate approaches 100% in rats; (ii) this technique can produce satisfactory experimental saccular aneurysms for other aneurysm studies, and in the future it will also be possible to use this technique to produce experimental saccular aneurysms in cerebral arteries of large animals.     

Involvement of internal elastic lamina in development of induced cerebral aneurysms in rats

To elucidate the role of the internal elastic lamina in the development of cerebral aneurysm, the bifurcation of the anterior cerebral artery and olfactory artery was histologically studied in control and experimental rats treated with unilateral carotid ligation and renal hypertension. Various stages of aneurysm formation were compared, and it was found that early aneurysmal changes were always present just distal to the apical intimal pad on the anterior cerebral artery side. The internal elastic lamina was thinned and fragmented just distal to the pad even in the very early stage of aneurysm formation when the medial layer was still present. In control rats, the internal elastic lamina had a tendency to thin and fragment at the site where aneurysms would develop in experimental rats. Our study shows that changes of the internal elastic lamina were present just distal to the pad even in control rats, which never develop cerebral aneurysms. Under hemodynamic stress augmented by experimental treatments, further degenerative changes of the internal elastic lamina and involvement of the medial layer are considered to occur and result in aneurysm formation there.     

选择性血管结扎法建立大鼠脑动脉瘤模型

目的 探讨选择性血管结扎法对大鼠脑动脉瘤形成的影响.方法 SD大鼠50只,随机分为3组:(1)A组20只:结扎左侧颈总动脉+两侧肾动脉后支(各侧1支);(2)B组20只:"8"字形结扎左侧颈内、外动脉+电凝并切断两侧肾动脉(各侧只留1个分支);(3)C组为假手术组10只.术后喂养含0.9%的盐及0.12%β-氨基丙腈的饲料.4周后处死,取大鼠脑动脉Willis环,在光镜下观察其病理的变化.结果 A组大鼠ACA/OA分叉处均未见有进展期动脉瘤,仅3个早期动脉瘤样改变.B组大鼠中发现12个进展期动脉瘤和2个早期动脉瘤样改变.C组中未见动脉瘤形成.结论 血管壁结构的破坏或变弱和高血液动力学压力是动脉瘤形成的主要因素.     

Elastic skeleton of intracranial cerebral aneurysms in rats

In an attempt to clarify the developmental mechanism of cerebral aneurysms, we studied the elastic skeleton of experimentally induced cerebral aneurysms in rats under scanning electron microscopy after hot formic acid extraction followed by freeze-drying. We produced cerebral aneurysms in 19 rats by unilaterally ligating the common carotid artery, inducing renal hypertension, and feeding beta-aminopropionitrile fumarate. The first noted change was the loss of folds protruding from the internal elastic lamina. Morphologic changes of the internal elastic lamina, considered to be primarily responsible for aneurysmal formation, occurred after the loss or disintegration of the elastic skeleton of first the intima, then the media. In large aneurysms with thick domes, we found proliferation of elastic lamellae that may reduce the risk of rupture. It seems probable that the complex elastic skeleton of the arterial wall may account for the mechanical properties of the artery and that growth of an aneurysm occurs due to disintegration of the elastic skeleton and not simply to rupture of the internal elastic lamina. We believe that such changes in the elastic skeleton are a property of the functional state of the cells that produce elastin.     

Animal model Of cerebral aneurysms: Pathology and pathogenesis of induced cerebral aneurysms in rats

Saccular cerebral aneurysms are induced in rats treated with ligation of one or both of the common carotid arteries, experimental hypertension, and β-aminopropionitrile feeding. Combination of ligation of the carotid artery and experimental hypertension is the minimal requirement for inducing aneurysms within a few months. β-aminopropionitrile makes the arterial wall fragile, increasing the incidence of aneurysmal development. Induced aneurysms are strongly related to haemodynamic stresses. They ere located on the large arteries at the base of the brain. Some of them apparently originate from the apex of bifurcation. The macroscopic and microscopic findings are generally in accordance with those of spontaneous lesions in man. The results of electron microscope and histochemical studies indicate the participation of leukocytes and their lysosomal enzymes in the development and growth of aneurysms. Adventitial cells are also suggested to be responsible for the growth of aneurysms.     

A novel haemodynamic cerebral aneurysm model of rats with normal blood pressure

Cerebral aneurysms of traditional animal models are usually too small to be imaged in vivo. A novel rat model induced by ligation of the unilateral common carotid artery and contralateral pterygopalatine and external carotid arteries was investigatid. To evaluate the morphological changes of the cerebral arteries, synchrotron radiation angiography was utilised at 1 month, 2 months and 3 months after induction. Cerebral aneurysms and expansion of anterior cerebral arteries in these rats were identified when the animals were alive. This novel model is useful for cerebral aneurysm research.     

人脑动脉瘤及其皮层小动脉组织72-和92-KDaⅣ型胶原酶mRNA的原位杂交研究

目的　应用原位杂交技术， 检测脑动脉瘤患者动脉瘤及其皮层小动脉标本中ＭＭＰ２ 、ＭＭＰ９、ＴＩＭＰ１、和ＴＩＭＰ２、的ｍＲＮＡ， 并定位产生它们的细胞。试图解释为什么脑动脉瘤的分布具有部位倾向性。方法　用地高辛标记的ＭＭＰ２、ＭＭＰ９、ＴＩＭＰ１、和ＴＩＭＰ２ ａｎｔｉｓｅｎｓｅ ｃＲＮＡ探针与脑动脉瘤及同一患者的皮层小动脉组织进行原位杂交， 定位产生它们的细胞。并用ｓｅｎｓｅ ｃＲＮＡ探针进行阴性对照。结果　所有脑动脉瘤标本中均见ＭＭＰ９ ｍＲＮＡ 阳性杂交信号。在内膜， 尤其是内弹力层部位， 阳性杂交信号密集存在。脑动脉瘤壁内弹力层消失。动脉瘤患者的皮层小动脉标本中未发现ＭＭＰ９ ｍＲＮＡ阳性杂交信号； 其内弹力层完整。在以上两种组织中均未发现ＭＭＰ２ 和ＴＩＭＰ１，２ ｍＲＮＡ的阳性杂交信号。结论　某些因素引起局部脑动脉的ＭＭＰ９ ｍＲＮＡ增多， 导致局部内弹力层断裂、消失， 甚至动脉壁全层结构的破坏， 从而进一步引发脑动脉瘤的形成， 而ＭＭＰ９ ｍＲＮＡ分布相对较少的部位无动脉瘤形成。     

Effect of contralateral carotid ligation on experimental carotid artery aneurysm in the rat.

Haemodynamic factors in the formation and development of saccular aneurysms have been widely studied. Saccular aneurysms could appear and grow at the side of the increased blood flow. The effects of contralateral carotid ligation on the formation and growth of our experimental saccular aneurysms were studied. Measurement and pathological examination showed that the haemodynamic changes could facilitate the development of saccular aneurysms, but by itself could not bring about their formation.