自发性高血压大鼠颈动脉中膜细胞外基质的变化--替米沙坦的干预研究  

Changs to the extracelluar matrix of carotid arterial media in spontaneously hypertensive rats:the intervention study of telmisartan

作　　者：陈宏[1,2] 洪华山[1] 江琼[1] 马建芳[2] 刘永平[2] 

机构地区：[1]福建医科大学附属协和医院心血管内科,福州350001 [2]南京军区福州总医院476医院,福州350002

出　　处：《中国药科大学学报》2008年第6期543-547,共5页Journal of China Pharmaceutical University

基　　金：福建医科大学附属协和医院重点学科基金资助项目~~

摘　　要：目的:研究自发性高血压大鼠(SHR)颈动脉中膜细胞外基质(ECM)的变化及替米沙坦对其的影响。方法:将12周龄的SHR随机分为高血压组、替米沙坦高剂量组(Tel-H)、替米沙坦低剂量组(Tel-L),另设同性别、同周龄的WKY大鼠为对照组(n=10),实验开始及每两周测鼠尾收缩压(SBP),18周后终止实验,麻醉后取颈总动脉,颈动脉切片。颈动脉中膜纤维黏连蛋白(FN)、层黏连蛋白(LN)的表达以SP免疫组化染色评估。结果:两周后Tel-H组的SBP显著低于SHR组(P<0.01),其降血压作用持续至实验结束,而Tel-L组SBP与SHR组比较差异无显著性(P>0.05);SHR组颈动脉中膜的FN、LN积分光密度(IOD)明显高于WKY组(P<0.01);Tel-H、Tel-L组颈动脉中膜FN、LN的IOD分别明显低于SHR组(P<0.05);颈动脉中膜FN、LN的IOD分别与MCSA呈显著正相关(r=0.954,0.859,P<0.01)。结论:30周龄SHR颈动脉中膜ECM发生了明显重构,表现为胶原、FN、LN沉积增多,而弹力纤维减少;替米沙坦治疗能减少上述ECM的改变,从而减轻颈动脉的重构。Aim： To investigate the changes to extracellular matrix （ECM） of carotid arterial media in the spontaneously hypertensive rats（SHRs） and the effect of telmisartan on ECM. Methods： 12 Week-old-male SHRs were randomized to three groups, including untreated SHR group（SHR）, telmisartan high dose group （Tel-H） and telmisartan low dose group（Tel-L）. Age and sex matched Wistar Kyoto rats （WKY） were served as control group. Systolic blood pressure （SBP） of rats was measured prior to and post treatment during period of weeks intervention, rats were sliced and the carotid arteries were cut out and collected. Fibronectin（FN） and laminin（LN） expression on the carotid arteries media were measured with immunohistochemistry staining. Results： After 2 weeks, SBP levels in Tel-H group were significantly decreased when compared to SHR group（ P 〈 0. 01）. Moreover, lower SBP in Tel-H group was sustained until the end of experiment. However, there was no significant difference between SHR group and Tel-L group （P 〉0.05）. The integrated optical density（IOD） of both FN and LN in the carotid arteries media in SHR group was markedly higher than those in WKY group respectively（ P 〈0. 01）. Furthermore, the IOD of FN and LN in the carotid arteries media in Tel-H and TelL group was markedly lower than those of SHR group respectively（ P 〈 0. 05）. IOD of both FN and LN in the carotid arteries media was positively correlated with MSCA of carotid arteries（ r = 0. 954, 0. 859, respectively; P 〈 0. 01 for each）. Conclusion： The ECM remodeling occurs in carotid arteries in 30-week-old SHR. Overdeposed collagen, FN and LN as well asdecreased elastic fiber are characteristics of ECM remodeling in the carotid artery of SHR. Telmisartan treatment could attenuate ECM remodeling through the down-regulation of collgen, FN and LN but the upregulation of elastic fiber expression on carotid artery of SHR.

关 键 词：替米沙坦 颈动脉重构 细胞外基质 自发性高血压大鼠 

分 类 号：R544.1[医药卫生—心血管疾病]