尾加压素Ⅱ对大鼠损伤血管基质金属蛋白酶的影响  

Urotensin Ⅱ’s effect on MMP in rat injured aortas

作　　者：张丽芳[1,2] 丁文惠[1] 史力斌[1] 李康[1,3] 柯元南[2] 唐朝枢[4] 

机构地区：[1]北京大学第一医院心内科,100034 [2]卫生部中日友好医院心内科 [3]卫生部北京医院心内科 [4]北京大学医学部生理学与病理生理学系/分子心血管学教育部重点实验室,100191

出　　处：《中国医药生物技术》2009年第5期335-338,共4页Chinese Medicinal Biotechnology

基　　金：国家自然科学基金(30270541)

摘　　要：目的观察外源性尾加压素II(UⅡ)及其拮抗剂Urantide对大鼠胸主动脉球囊拉伤模型损伤动脉基质金属蛋白酶-1(MMP-1)、MMP-2和组织基质金属蛋白酶抑制剂-2(TIMP-2)的影响。方法构建大鼠胸主动脉球囊拉伤模型,分为4组:假拉伤组、单纯拉伤组、拉伤术后持续皮下给予UII(1nmol·kg-1·h-1)的UII组、拉伤术后持续皮下给予Urantide(10nmol·kg-1·h-1)的Urantide组。21d后,采用RT-PCR方法检测各组UII受体G蛋白偶联受体-14(GPR-14)的表达,免疫组化和明胶酶谱法检测MMP-1、MMP-2、TIMP-2的表达水平与活性。结果①单纯拉伤组血管GPR-14mRNA相对表达量(0.66±0.09)明显高于假拉伤组(0.42±0.06),为其1.6倍(P<0.05);②与单纯拉伤组相比,UII组GPR-14mRNA相对表达量增高(0.93±0.06,P<0.05),MMP-1表达降低(8.3±1.8vs3.3±0.8,P<0.05),MMP-2活性高至其1.25倍(137±24vs172±8,P<0.05),TIMP-2表达降低(14.8±2.4vs4.0±0.8,P<0.05);③与单纯拉伤组相比,Urantide组GPR-14mRNA相对表达量降低(0.37±0.08,P<0.05),MMP-1表达差异无统计学意义,MMP-2活性高至其1.29倍(177±21,P<0.05),TIMP-2表达降低(6.6±1.2,P<0.05)。结论大鼠胸主动脉损伤后局部GPR-14mRNA水平上调,外源性应用UⅡ后,GPR-14mRNA水平进一步上调,MMP-1表达下降,TIMP-2表达减少,MMP-2活性升高。应用Urantide(10nmol·kg-1·h-1)能抑制GPR-14mRNA的水平上调,但对MMP-1的表达无明显影响,未能表现出拮抗胶原沉积的作用,甚至对MMP-2/TIMP-2平衡有类UⅡ的作用,其意义有待进一步研究。Objective To evaluate Urotensin Ⅱ （UII） and its antagonist, Urantide＇s effect on matrix mettalloproteinases （MMP-1, MMP-2 and tissue inhibitors of mettalloproteinases-2 （TIMP-2） in rat balloon injured aortas. Methods Stenosis model of thoracic aorta 21 days after balloon injury was established in male Wistar rats, which were divided into 4 groups, including uninjured, injured, UII （1 nmol·kg-1.h-1, UII group） and Urantide （10 nmol.kg-1.h-1, Urantide group）, infused by osmotic mini-pump, respectively. The expression and activity of UII receptor GPR-14, MMP-1, MMP-2, TIMP-2 were detected by RT-PCR, immunohistochemical staining and gel zymography, respectively. Results （1）In injured group, compared with uninjured group （0.42 ±0.06）, GRP-14 mRNA increased 1.6 fold （0.66±0.09, P 〈 0.05）; （2）Compared with injured group, UII group got a higher GRP-14 mRNA （0.93 ± 0.06, P 〈 0.05）, lower MMP-1 （8.3± 1.8 vs 3.3± 0.8, P 〈 0.05）, the activity of MMP-2 increased to 1.25 fold （137±24 vs 172 ± 8, P 〈 0.05）, T1MP-2 was lower （14.8 ±2.4 vs 4.0± 0.8, P 〈 0.05）; （3）Compared with injured group, Urantide group got a lower GRP-14 mRNA （0.37 ±0.08, P 〈 0.05）, MMP-I had no significant, the activity of MMP-2 increased to 1.29 fold （177 ± 21, P 〈 0.05）, TIMP-2 was lower （6.6 ± 1.2, P 〈 0.05）. Conclusions In injured group, GRP-14 mRNA up-regulates. Exogenous UII stimulated GRP-14 mRNA further up-regulation, the expression of MMP-I and TIMP-2 decreased, and the activity of MMP-2 increased. Urantide （10 nmol.kg-1.h-1） could antagonize GRP-14 mRNA up-regulation, but had no effect on MMP-1, and had a similar tendency as UII on MMP-2/TIMP-2 balance, which needs further research.

关 键 词：尿紧张素类 基质金属蛋白酶类 冠状动脉再狭窄 血管内膜 

分 类 号：R543[医药卫生—心血管疾病]