自发性高血压大鼠颈动脉中膜基质金属蛋白酶-9和基质金属蛋白酶抑制剂-2的表达及替米沙坦的干预作用  

Expression of MMP-9 and TIMP-2 of carotid arterial media in spontaneously hypertensive rats and the intervention study of telmisartan

作　　者：陈宏[1] 刘永平[1] 马建芳[1] 张都生[2] 江琼[2] 

机构地区：[1]南京军区福州总医院476医院 [2]福建医科大学附属协和医院心血管内科

出　　处：《中国临床药理学与治疗学》2008年第8期865-869,共5页Chinese Journal of Clinical Pharmacology and Therapeutics

摘　　要：目的:观察自发性高血压大鼠(SHR)颈动脉基质金属蛋白酶-9(MMP-9)和基质金属蛋白酶抑制剂-2(TIMP-2)的表达,并探讨替米沙坦对其的干预作用。方法:30只雄性12周龄的SHR随机分为3组:高血压组(SHR)、替米沙坦低剂量组(TelL)、替米沙坦高剂量组(TelH),并设同周龄雄性的WKY大鼠为对照组(WKY,n=10)。干预18周,观察各组大鼠SBP、颈动脉中膜胶原面积百分比。用免疫组化评估MMP-9和TIMP-2在颈动脉中膜的表达水平。结果:两周后TelH组SBP明显低于SHR组(P<0.01),其降压作用持续至实验结束,而TelL组SBP与SHR组无统计学差异(P>0.05)。SHR组中膜胶原面积百分比明显高于WKY组(P<0.01),TelH、TelL组的中膜胶原面积百分比低于SHR组(P<0.05)。SHR组中膜MMP-9的吸光度值(IOD)明显低于WKY组(P<0.01),TelH、TelL组中膜MMP-9的IOD值高于SHR组(P<0.05)。SHR组中膜TIMP-2的IOD值明显高于WKY组(P<0.01),TelH、TelL组中膜TIMP-2的IOD值低于SHR组(P<0.05)。结论:SHR颈动脉中膜MMP-9表达减少,TIMP-2表达增多,替米沙坦能通过降压及上调MMP-9、下调TIMP-2的表达,从而减轻颈动脉的纤维化。AIM： To investigate the expression and the effects of telmisartan on the matrix metalloproteinase-9 （MMP-9） and the tissue inhibitor of inetalloproteinase-2（TIMP-2） of carotid arterial media in spontaneously hypertensive rots （SHRs）. METHODS： 12 week-old male SHRs were randomized to untreated SHR group （SHR）, telmisartan high dose group （TelH） and telmisartan low dose group（TelL） （ n = 10 for each）. Age and sex matched Wistar Kyoto rats （WKY） were served as control group （n = 10）. After 18 weeks intervention, systolic blood pressure （SBP） of rats and area of collagen fiber percentage were measured. MMP-9 and TIMP-2 expression levels in the carotid arterial media were evaluated with immunohistochemistry staining. RESULTS： After 2 weeks, the SBP level in TelH group was significantly decreased compared to SHR group （P 〈 0.01 ）. And the SBP lowering effect in TelH group was kept during the experiment. However, there was no significant difference between SHR group and TelL group （ P 〉 0.05 ）. The area of collagen percentage in carotid arterial media of SHR group were higher than that in WKY group （ P 〈0.01）. In TelH and TelL group the areas were lower than that in SHR group respectively （P 〈 0.05 for each）. The integrated optical density（OD）of MMP-9 in the carotid arterial media in SHR group was markedly lower than that in WKY group（P 〈0.01）. The OD in TelH and TelL group was higher than that of SHR group respectively （P 〈 0.05 for each）. The OD of TIMP-2 in the carotid arterial media in SHR group was markedly higher than that in WKY group（ P 〈 0.01 ）. In TelH and TelL group it was markedly lower than that of SHR group respectively（ P 〈 0.05 for each）. CONCLUSION： MMP-9 expression level decreased but TIMP-2 level increased in carotid arterial media of SHRs. Telmisartan could attenuate carotid arteries fibrosis through decreasing SBP, upregulating MMP-9 and downregulating TIMP-2 expression levels on carotid arteries of S

关 键 词：自发性高血压大鼠 颈动脉 基质金属蛋白酶-9 基质金属蛋白酶抑制剂-2 替米沙坦 

分 类 号：R965.2[医药卫生—药理学]