【摘要】： 目的 探討實驗性大鼠高血壓腦動脈瘤形成及腦血管早期病理改變與腦動脈瘤形成的關(guān)系。 材料和方法 1、實驗材料 選用雄性S-D大鼠75只，年齡6—7周，體重200-250克，動物及實驗室均由中國醫(yī)科大學(xué)附屬盛京醫(yī)院動物實驗中心提供。 2、實驗方法 (1)動物分組 將75只SD大鼠隨機分進A，B，C三組，A組(實驗組)：SD大鼠30只，全部左頸總動脈結(jié)扎+經(jīng)腹正中入路行雙腎動脈后支電凝+術(shù)后1周1％鹽水代替飲用水；B組(高血壓組)：SD大鼠30只，經(jīng)大鼠腹正中入路行雙腎動脈后支電凝+術(shù)后1周1％鹽水喂養(yǎng)；C組(正常對照組)：不處理+自來水喂養(yǎng) (2)鼠尾動脈血壓的測量 所有SD實驗大鼠術(shù)前1天測量鼠尾動脈壓作為基礎(chǔ)血壓。并分別在手術(shù)后2周，6周，10周及處死前測量血壓。 (3)大鼠顱內(nèi)動脈瘤標本的獲取 12周后，全部大鼠在全麻下(方法同上)，通過開胸左心室插管至升主動脈處，先用生理鹽水30ml經(jīng)導(dǎo)管灌注，同時剪開腔靜脈排放血液，然后用4％多聚甲醛／0.1M磷酸緩沖液(pH7.4)120ml經(jīng)導(dǎo)管緩慢注入，當灌注固定后將大鼠斷頸，開顱取腦，在10—16倍手術(shù)顯微鏡下將Willis環(huán)仔細分離取出，再在40倍顯微鏡下檢查Willis環(huán)，尤其是右側(cè)的大腦前動脈一嗅動脈(anterior cerebralartery-olfactoryartery，ACA-OA)段的動脈瘤樣改變。 (4)動脈瘤標本的光鏡觀察 10％甲醛固定，酒精梯度脫水，石蠟包埋切片，常規(guī)HE染色。 (5)動脈瘤標本的透射電鏡檢查 將動脈瘤標本浸泡于2.5％戊二醛中預(yù)固定24小時，1％四氧化餓再固定，丙酮逐級脫水，Epon812包埋，半薄切片光學(xué)定位，超薄切片醋酸鈾及構(gòu)椽酸鉛雙重染色，超薄切片用JEM-1200EX型透射電鏡觀察，拍片。 3、統(tǒng)計學(xué)方法 用SPSS for Windows10.0作實驗組和對照組不同時間點收縮壓的t檢驗，P＜0.01時，差異有顯著性意義。 實驗結(jié)果 1、生存情況 試驗組存活28只，高血壓組存活29只，正常對照組全部存活。3只死亡大鼠死因不明，不排除為惡性高血壓致死。 2、血壓變化 實驗組和高血壓組自第2周起比對照組血壓顯著升高，以后血壓穩(wěn)步上升。正常對照組血壓則保持在正常范圍。方差分析結(jié)果：A組和B組血壓不能認為有差異(P＞0.05)；A，B兩組與C組的血壓差異有顯著性意義(P＜0.01) 3、光鏡和電鏡觀察結(jié)果 A組生存的28只大鼠顯微鏡下共出現(xiàn)10個動脈瘤，均在ACA—OA分叉處。動脈瘤前期6例，早期動脈瘤3例，進展期腦動脈瘤1例，余13例，B組29只和C組15只大鼠在動脈分叉處及主干上均未見動脈瘤樣結(jié)構(gòu)改變。 討論 顱內(nèi)動脈瘤破裂常表現(xiàn)為自發(fā)性蛛網(wǎng)膜下腔出血(SAH)和顱內(nèi)血腫，致殘率和死亡率很高。如果對該病的發(fā)病機制有正確的認識并采取及時有效的診斷、干預(yù)和治療，該病的預(yù)后將會明顯改善。因此探討動脈瘤的病理形態(tài)、演變過程和臨床治療具有重要的意義。由于臨床上對動脈瘤無法研究動脈瘤的形成、發(fā)展過程，所以建立和研究經(jīng)濟、有效的腦動脈瘤動物模型，揭示其發(fā)病機理十分重要。 大鼠腦動脈瘤模型則具有經(jīng)濟、動脈瘤通暢率高(由于動脈搏動快，發(fā)生血栓可能性小)，血管不易痙攣等優(yōu)點，而且較符合人類腦動脈瘤的病理生理改變。 大鼠腎性高血壓導(dǎo)致腦動脈瘤的發(fā)生率在10％～30％之間，本組腦動脈瘤樣改變的發(fā)生率為36％(10／28)，其原因可能與試驗組無感染，生存率較高，成功誘導(dǎo)高血壓有關(guān)系。而腦動脈瘤全部是發(fā)生在頸總動脈非結(jié)扎側(cè)動脈ACA—OA分叉部，，其原因與血流動力學(xué)改變和該處動脈壁發(fā)生退行性變有關(guān)。在高血壓的基礎(chǔ)上，結(jié)扎一側(cè)頸總動脈增加了對側(cè)的腦灌注，在巨大的血流沖擊下，軸心血流沖擊ACA-OA分叉部導(dǎo)致局部血管壁內(nèi)彈力膜破壞、內(nèi)皮細胞受損、血管彈力組織和平滑肌層及動脈瘤壁中的膠原受損，致使動脈瘤形成。 總之，實驗性大鼠高血壓腦動脈瘤模型是經(jīng)濟、有效的腦動脈瘤動物模型，其成瘤率高且與人類顱內(nèi)動脈瘤部位及病理生理改變相似，特別在腦微動脈瘤形成、發(fā)展過程的方面具有研究價值。 結(jié)論 血液動力學(xué)壓力增高改變結(jié)合Willis環(huán)一側(cè)過度灌注的腦血流是建立顱內(nèi)動脈瘤動物模型的基本條件，其引起的內(nèi)彈力膜與平滑肌的破壞是腦動脈瘤發(fā)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
【學(xué)位授予單位】：中國醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2007
【分類號】：R-332

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相關(guān)期刊論文 前1條

1 郭予大;韓天旺;郭付有;游潮;;大鼠雙側(cè)腎動脈后支結(jié)扎術(shù)制作腎性高血壓模型[J];中華實驗外科雜志;2006年01期

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