基质金属蛋白酶-2和基质金属蛋白酶-9在大鼠脑动脉瘤形成的作用及其机制  

Effect of matrix metalloproteinases - 2 and matrix metalloproteinases - 9 on the cerebral aneurysm formation in rats

作　　者：张宇[1] 邢立举[1] 翟秀伟[1] 

机构地区：[1]大庆龙南医院神经外科,黑龙江163000

出　　处：《中华实验外科杂志》2015年第12期3066-3070,共5页Chinese Journal of Experimental Surgery

摘　　要：目的探讨基质金属蛋白酶（MMP）-2、MMP-9在大鼠脑动脉瘤形成过程中的作用及其机制。方法将健康成年雄性SD大鼠60只，随机分为MMP组和高血压组，每组30只，前者应用外源性MMP-2、MMP-9干预，后者通过手术造成大鼠肾性高血压，分别于术后1、3和5周采集标本，观察脑动脉瘤形成，并应用酶联免疫吸附试验（ELISA）法、免疫组织化学法和反转录一聚合酶链反应（1iT—PCR）检测MMP及其表达水平。结果MMP组大鼠血压稳定，保持在（106．42±11．45）mmHg（1mmHg=0．133kPa）。高血压组大鼠术前血压为（105．36±11．24）mmHg，术后1周血压迅速上升，达（150．66±13．49）mmHg，术后3周时血压已接近升压曲线峰值（194．73±16．91）mmHg，高于术前血压，差异有统计学意义（P〈0．05），以后血压逐渐保持平稳，形成稳定的肾性高血压。两组血压在术后1、3、5周差异均有统计学意义（P〈0．05）。病理学观察见13只大鼠的脑底动脉环分叉部有明显动脉瘤形成，MMP组脑底动脉环结构基本正常。MMP组在术前，术后1周，3周和5周的血浆MMP-2和MMP-9浓度分别为（56．23±3．47）、（74．51±4．92）、（79．92±6．51）、（85．96±7．38）mg／L和（61．57±2．62）、（73．85±4．63）、（80．77±7．23）、（87．94±9．50）mg／L。高血压组在术前，术后1周，3周和5周的血浆MMP-2和MMP-9浓度分别为（58．22±4．45）、（73．52±5．83）、（108．59±8．64）、（129．47±12．49）mg／L和（63．24±3．72）、（76．72±6．58）、（135．26±14．74）、（159．03±17．27）mg／L。在术后3、5周，与MMP组比较差异均有统计学意义（P〈0．05）。免疫组织化学见高血压组在术后3周脑动脉壁胞质中MMP-2和MMP-9表达明显增加，持续至第5周，而MMP组仅有弱阳性表达。RT—PCR检测显示高血压组在术后3周脑动脉壁MMP-2和MMP-9基因表达增加�Objective To explore the effect of matrix metalloproteinases （MMP） -2 and MMP -9 on the cerebral aneurysm formation in rats. Methods Sixty healthy male adult SD rats were randomly di- vided into MMP group and hypertension group （30 cases per group）. The rats in MMP group were adminis- trated with exogenous MMP -2 and MMP -9, and those in hypertension group were subjected to operation to induce renal hypertension. Specimens were collected at 1st, 3rd and 5th week after operation. Formative cerebral aneurysms were observed. The dynamic changes of MMP -2 and MMP -9 expression were exam- ined by enzyme linked immunosorbent assay （ELISA） , reverse transcriptase - polymerase chain reaction （RT- PCR ）, and immunohistochemistry. Results Blood pressure was （106.42 ± 11.45） mmHg （1 mmHg = 0. 133 kPa） in MMP group. The blood pressure in hypertensive group was （ 105.36 ±_ 11.24） mmHg, the blood pressure was（ 150. 66 ± 13.49） mmHg, increased rapidly after 1 weeks, blood pressure was （ t94.73 ± 16.91 ） mmHg 3 weeks after operation, closing to the peak. They were higher than that of preoperative, the difference was statistically significant （P 〈 0. 05）. The blood pressure of the two groups was statistically significant after 1, 3 and 5 after operation （ P 〈 0. 05 ）. Aneurysms were obvi- ous in the bifurcations of Wills arterial ring in 13 rats ; the structure of Wills arterial ring was basically nor- mal in MMP group. The plasma concentrations of MMP - 2 and MMP - 9 in MMP group were （56. 23 ±3.47）, （74.51 ±4.92）, （79.92±6.51）, （85.96 ±7.38） mg/L and （61.57 ±2.62）, （73.85 ± 4. 63 ） , （ 80. 77 ± 7. 23 ） , （ 87. 94 ± 9. 50 ） mg/L preoperative, 1, 3 and 5 weeks after operation. The plasma concentrations of MMP - 2 and MMP - 9 in hypertensive group were （ 58.22 ± 4. 45 ）, （ 73.52 ± 5.83 ）, （ 108. 59 ± 8. 64）, （ 129.47 ± 12.49 ） mg/L and （63.24 ± 3.72）, （76. 72 ± 6. 58 ）, （ 135.26 ± 14. 74）, （ 159.03 ± 17

关 键 词：金属基质蛋白酶-2 金属基质蛋白酶-9 脑动脉瘤 

分 类 号：R735.2[医药卫生—肿瘤]